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Yang Z, Liu S, Hu L, Chen J, Wang J, Pan Y, Xu L, Liu M, Chen M, Xi M, Zhang Y. Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm. JHEP Rep 2024; 6:101151. [PMID: 39308987 PMCID: PMC11416668 DOI: 10.1016/j.jhepr.2024.101151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 09/25/2024] Open
Abstract
Background & Aims Radiation therapy has been refined with increasing evidence of the benefits of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤5.0 cm. Methods Patients with a single HCC lesion ≤5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate, progression-free survival, overall survival, adverse events and subsequent treatments after recurrence were analyzed. Results A total of 288 patients receiving RFA (n = 166) or SBRT (n = 122) were enrolled. The baseline characteristics between the two groups were comparable. The cumulative local recurrence rate in the SBRT group was significantly lower than that in the RFA group (hazard ratio [HR] 0.30, 95% CI 0.16-0.57, p <0.001), especially for patients with tumours >2.0 cm (HR 0.20, 95% CI 0.08-0.50, p <0.001) or adjacent to major vessels (HR 0.29, 95% CI 0.13-0.66, p <0.001). Cumulative distant recurrence rate, progression-free survival and overall survival were not significantly different between the two groups (all p >0.050). Adverse events were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and total bilirubin increases. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (p <0.001). Conclusions Both RFA and SBRT were effective and safe for HCC with a single lesion ≤5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumours >2.0 cm or adjacent to major vessels. Impact and implications Stereotactic body radiation therapy (SBRT) may be used as an alternative treatment to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumours >3 cm and those with 1 to 3 tumours. This study focused on HCC patients with a specific tumour burden, namely a single lesion ≤5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumours >2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.
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Affiliation(s)
- Zhoutian Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Shiliang Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Li Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Jinbin Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Juncheng Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Yangxun Pan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Li Xu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Mengzhong Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Minshan Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Mian Xi
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
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Lazzarotto-da-Silva G, Scaffaro LA, Farenzena M, Prediger L, Silva RK, Feier FH, Grezzana-Filho TJM, Rodrigues PD, de Araujo A, Alvares-da-Silva MR, Marchiori RC, Kruel CRP, Chedid MF. Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation. World J Transplant 2024; 14:90571. [PMID: 38947974 PMCID: PMC11212594 DOI: 10.5500/wjt.v14.i2.90571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/12/2024] [Accepted: 04/03/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. RESULTS Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.
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Affiliation(s)
- Gabriel Lazzarotto-da-Silva
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Leandro A Scaffaro
- Department of Interventional Radiology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Mauricio Farenzena
- Department of Interventional Radiology Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Lucas Prediger
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Rafaela K Silva
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Flávia Heinz Feier
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Tomaz J M Grezzana-Filho
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Pablo D Rodrigues
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Alexandre de Araujo
- Department of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Mario Reis Alvares-da-Silva
- Department of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Roberta C Marchiori
- Department of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Cleber Rosito Pinto Kruel
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
| | - Marcio Fernandes Chedid
- Department of Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
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Mosenthal M, Adams W, Cotler S, Ding X, Borge M, Malamis A, Lee D, Thomas T, Jawahar A, Amin P, Molvar C. Locoregional Therapies for Hepatocellular Carcinoma prior to Liver Transplant: Comparative Pathologic Necrosis, Radiologic Response, and Recurrence. J Vasc Interv Radiol 2024; 35:506-514. [PMID: 38123127 DOI: 10.1016/j.jvir.2023.12.009] [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: 05/25/2023] [Revised: 11/30/2023] [Accepted: 12/08/2023] [Indexed: 12/23/2023] Open
Abstract
PURPOSE To compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence. MATERIALS AND METHODS Consecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed. RESULTS Seventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)-63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN. CONCLUSIONS Radiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.
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Affiliation(s)
- McKenzie Mosenthal
- Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| | - William Adams
- Public Health Sciences, Loyola University Medical Center, Maywood, Illinois
| | - Scott Cotler
- Department of Medicine, Loyola University Medical Center, Maywood, Illinois
| | - Xianzhong Ding
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Marc Borge
- Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| | - Angelo Malamis
- Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| | - David Lee
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Tarita Thomas
- Department of Radiation Oncology, Northwestern Memorial Hospital, Chicago, Illinois
| | | | - Parag Amin
- Department of Radiology, Cleveland Clinic Florida, Weston, Florida
| | - Christopher Molvar
- Department of Radiology, Loyola University Medical Center, Maywood, Illinois; Edward Hines Jr. Veterans Affairs Hospital, Hines, Illinois.
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Eguia E, Baker T, Baker M. Hepatocellular Carcinoma: Surgical Management and Evolving Therapies. Cancer Treat Res 2024; 192:185-206. [PMID: 39212922 DOI: 10.1007/978-3-031-61238-1_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. It is also the second leading cause of cancer death worldwide, with 780,000 deaths in 2018. Seventy-two percent of HCC cases occur in Asia, 10% in Europe, 8% in Africa, 5% in North America, and 5% in Latin America (Singal et al. in J Hepatol 72(2):250-261, 2020 [1]).
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Affiliation(s)
- Emanuel Eguia
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Talia Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA
| | - Marshall Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA.
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Dupré A, Rivoire M, Metzger S, Cropet C, Vincenot J, Peyrat P, Chen Y, Pérol D, Melodelima D. Intra-operative High-Intensity Focused Ultrasound in Patients With Colorectal Liver Metastases: A Prospective Ablate-and-Resect Study. ULTRASOUND IN MEDICINE & BIOLOGY 2023; 49:1845-1851. [PMID: 37268553 DOI: 10.1016/j.ultrasmedbio.2023.04.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/07/2023] [Accepted: 04/21/2023] [Indexed: 06/04/2023]
Abstract
OBJECTIVE High-intensity focused ultrasound (HIFU) is a recent, non-ionizing and non-invasive technology of focal destruction. Independence from the heat-sink effect of blood flow makes HIFU an interesting technique for focal ablation of liver tumors. Current available technology is based on extracorporeal treatment that limits use of HIFU for the treatment of liver tumors, as elementary ablations are small and must be juxtaposed to treat tumors, resulting in long-duration treatment. We developed an HIFU probe with toroidal technology, which increases the volume of ablation, for intra-operative use, and we assessed the feasibility and efficacy of this device in patients with colorectal liver metastasis (CLM) measuring less than 30 mm. METHODS This study was an ablate-and-resect, prospective, single-center, phase II study. All ablations were performed in the area of liver scheduled for liver resection to avoid loss of chance of recovery. The primary objective was to ablate CLM with safety margins (>5 mm). RESULTS Between May 2014 and July 2020, 15 patients were enrolled and 24 CLM were targeted. The HIFU ablation time was 370 s. In total, 23 of 24 CLM were successfully treated (95.8%). No damage occurred to extrahepatic tissues. HIFU ablations were oblate shaped with an average long axis of 44.3 ± 6.1 mm and an average shortest axis of 35.9 ± 6.7 mm. On pathological examination, the average diameter of the treated metastasis was 12.2 ± 4.8 mm. CONCLUSION Intra-operative HIFU can safely and accurately produce large ablations in 6 min with real-time guidance (ClinicalTrials.gov identifier: NCT01489787).
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Affiliation(s)
- Aurélien Dupré
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France; LabTAU, INSERM, Université Lyon 1, Centre Léon Bérard, Lyon, France.
| | - Michel Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France; LabTAU, INSERM, Université Lyon 1, Centre Léon Bérard, Lyon, France
| | | | - Claire Cropet
- DRCI, Biostatistics Unit, Centre Léon Bérard, Lyon, France
| | - Jérémy Vincenot
- LabTAU, INSERM, Université Lyon 1, Centre Léon Bérard, Lyon, France
| | - Patrice Peyrat
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Yao Chen
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - David Pérol
- DRCI, Biostatistics Unit, Centre Léon Bérard, Lyon, France
| | - David Melodelima
- LabTAU, INSERM, Université Lyon 1, Centre Léon Bérard, Lyon, France
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Yu H. Editorial Comment: Complete Pathologic Necrosis of Early Hepatocellular Carcinoma After Pre-Liver Transplant Locoregional Therapy-Why Does It Matter? AJR Am J Roentgenol 2023; 220:735. [PMID: 36475818 DOI: 10.2214/ajr.22.28816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Hyeon Yu
- The University of North Carolina at Chapel Hill, Chapel Hill, NC
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Domini J, Makary MS. Single-center analysis of percutaneous ablation in the treatment of hepatocellular carcinoma: long-term outcomes of a 7-year experience. Abdom Radiol (NY) 2023; 48:1173-1180. [PMID: 36717404 DOI: 10.1007/s00261-023-03819-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/15/2023] [Accepted: 01/16/2023] [Indexed: 02/01/2023]
Abstract
PURPOSE The objective of this study is to examine the safety and efficacy of ablative therapy for hepatocellular carcinoma (HCC). METHODS A retrospective review of 419 consecutive patients diagnosed with HCC, treated with percutaneous ablation at a tertiary academic medical center from June 2015 to June 2022, was conducted. Data evaluated included demographics, disease and tumor burden scores, and functional status. Procedural outcomes included procedural course, complication rates, biochemical and radiologic response, survival, and functional status. RESULTS A total of 419 patients, including 313 males (74.7%) and 106 females (25.3%) with a mean age of 63.8 ± 6.64 years, made up the study cohort. 120 patients (28.6%) presented with solitary lesions and 299 patients (71.4%) had multifocal involvement, with a mean tumor size of 2.3 ± 0.92 cm. A majority of the interventions performed were microwave ablations (n = 413, 98.3%), with 6 radiofrequency ablations (1.4%). Treatment response was radiographically assessed up to 6 months post-ablation and graded as complete response (96.2%), partial response (2.6%), stable disease (0%), and progressive disease (1.2%). 97 (23.2%) of the treated patients went on to receive liver transplant. The average progression-free survival in the study population was 24 months with a survival of 85.9% (n = 360), 67.8% (n = 284), and 63.2% (n = 265) at 1 year, 3 years, and 5 years respectively. Functional outcomes, as defined by ECOG scores, were maintained or improved in 383 patients (91.4%) and 349 patients (83.3%) at 6 months and 12 months respectively. CONCLUSIONS This large institutional experience demonstrated safety and efficacy of ablation therapies for treatment of HCC with promising tumor response rates and enduring clinical outcomes including prolonged survival and preserved functional status.
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Affiliation(s)
- John Domini
- Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12Th Ave, 4Th Floor Faculty Office Tower, Columbus, OH, 43210, USA
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12Th Ave, 4Th Floor Faculty Office Tower, Columbus, OH, 43210, USA.
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Lazzarotto-da-Silva G, Grezzana-Filho TJM, Scaffaro LA, Farenzena M, Silva RK, de Araujo A, Arruda S, Feier FH, Prediger L, Lazzaretti GS, Alvares-da-Silva MR, Chedid AD, Kruel CRP, Chedid MF. Percutaneous ethanol injection is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation. Langenbecks Arch Surg 2023; 408:26. [PMID: 36639606 DOI: 10.1007/s00423-022-02750-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 10/20/2022] [Indexed: 01/15/2023]
Abstract
PURPOSE Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE. METHODS All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed. RESULTS One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82). CONCLUSION Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.
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Affiliation(s)
- Gabriel Lazzarotto-da-Silva
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Tomaz J M Grezzana-Filho
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Leandro A Scaffaro
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Mauricio Farenzena
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Rafaela K Silva
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Alexandre de Araujo
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Soraia Arruda
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Flavia H Feier
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Lucas Prediger
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Glória S Lazzaretti
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Mario R Alvares-da-Silva
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Aljamir D Chedid
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Cleber R P Kruel
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil
| | - Marcio F Chedid
- Liver Transplant and Hepatobiliary Surgery Unit, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Rua Ramiro Barcelos 2350, Sixth Floor, Room 600, Porto Alegre, 91340-400, Brazil.
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Wang X, Sun X, Lei Y, Pei J, Ma K, Feng K, Lau WY, Xia F. Open Radiofrequency Ablation Combined with Splenectomy and Pericardial Devascularization vs. Liver Transplantation for Hepatocellular Carcinoma Patients with Portal Hypertension and Hypersplenism: A Case-Matched Comparative Study. J INVEST SURG 2023; 36:1-7. [DOI: 10.1080/08941939.2022.2130482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Xishu Wang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Hygienic Company of 65529 Troops of PLA, Liaoyang, Liaoning, China
| | - Ximin Sun
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Yongrong Lei
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Jun Pei
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Kuansheng Ma
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Kai Feng
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Wan Yee Lau
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
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10
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Nevarez NM, Chang GY, Yopp AC. An Overview of Clinical Trials in the Treatment of Resectable Hepatocellular Carcinoma. Surg Oncol Clin N Am 2023; 32:101-117. [PMID: 36410911 DOI: 10.1016/j.soc.2022.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Partial hepatectomy, one of a few curative therapeutic modalities, is plagued by high recurrence rate of up to 70% at 5 years. Throughout the past 3 decades, many clinical trials have attempted to improve HCC recurrence rate following partial hepatectomy using adjuvant and neoadjuvant treatment modalities such as antiviral therapy, brachytherapy, systemic chemotherapy, immunotherapy, transarterial chemoembolization and radioembolization, and radiotherapy. The goal of this review is to discuss the clinical trials pertaining to resectable HCC including surgical technique considerations, adjuvant, and neoadjuvant treatment modalities.
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Affiliation(s)
- Nicole M Nevarez
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
| | - Gloria Y Chang
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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11
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Garg T, Shrigiriwar A, Habibollahi P, Cristescu M, Liddell RP, Chapiro J, Inglis P, Camacho JC, Nezami N. Intraarterial Therapies for the Management of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14143351. [PMID: 35884412 PMCID: PMC9322128 DOI: 10.3390/cancers14143351] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
Image-guided locoregional therapies play a crucial role in the management of patients with hepatocellular carcinoma (HCC). Transarterial therapies consist of a group of catheter-based treatments where embolic agents are delivered directly into the tumor via their supplying arteries. Some of the transarterial therapies available include bland embolization (TAE), transarterial chemoembolization (TACE), drug-eluting beads-transarterial chemoembolization (DEB-TACE), selective internal radioembolization therapy (SIRT), and hepatic artery infusion (HAI). This article provides a review of pre-procedural, intra-procedural, and post-procedural aspects of each therapy, along with a review of the literature. Newer embolotherapy options and future directions are also briefly discussed.
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Affiliation(s)
- Tushar Garg
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Apurva Shrigiriwar
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Peiman Habibollahi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Mircea Cristescu
- Vascular and Interventional Radiology Division, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
| | - Robert P. Liddell
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Julius Chapiro
- Section of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Peter Inglis
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA;
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL 34239, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
- Correspondence:
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12
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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.
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13
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Wei M, Lin M, Zhong X, Dai Z, Shen S, Li S, Peng Z, Kuang M. Role of Preoperational Imaging Traits for Guiding Treatment in Single ≤ 5 cm Hepatocellular Carcinoma. Ann Surg Oncol 2022; 29:5144-5153. [DOI: 10.1245/s10434-022-11344-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
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14
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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15
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Crocetti L, Bozzi E, Scalise P, Bargellini I, Lorenzoni G, Ghinolfi D, Campani D, Balzano E, De Simone P, Cioni R. Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation. Cancers (Basel) 2021; 13:5558. [PMID: 34771720 PMCID: PMC8583584 DOI: 10.3390/cancers13215558] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 02/08/2023] Open
Abstract
Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.
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Affiliation(s)
- Laura Crocetti
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
| | - Elena Bozzi
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Paola Scalise
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Irene Bargellini
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Giulia Lorenzoni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Daniela Campani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Pathology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy
| | - Emanuele Balzano
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Paolo De Simone
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Roberto Cioni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
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16
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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.
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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
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17
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Som A, Reid NJ, DiCapua J, Cochran RL, An T, Uppot R, Zurkiya O, Wehrenberg-Klee E, Kalva S, Arellano RS. Microwave Ablation as Bridging Therapy for Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: A Single Center Experience. Cardiovasc Intervent Radiol 2021; 44:1749-1754. [PMID: 34231009 DOI: 10.1007/s00270-021-02873-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 05/17/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival. MATERIALS AND METHODS A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests. RESULTS The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively). CONCLUSIONS Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma. CEBM LEVEL OF EVIDENCE Level 3, non-randomized controlled cohort study/follow-up study.
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Affiliation(s)
- Avik Som
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Nicholas J Reid
- Harvard Medical School, 25 Shattuck Ave, Boston, MA, 02120, USA
| | - John DiCapua
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Rory L Cochran
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Thomas An
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Raul Uppot
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Omar Zurkiya
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Eric Wehrenberg-Klee
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Sanjeeva Kalva
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA
| | - Ronald S Arellano
- Division of Interventional Radiology, Massachusetts General Hospital, 55 Fruit Street, GRB 293, Boston, MA, 02114, USA.
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Dikilitas M. Why Adjuvant and Neoadjuvant Therapy Failed in HCC. Can the New Immunotherapy Be Expected to Be Better? J Gastrointest Cancer 2021; 51:1193-1196. [PMID: 32869146 DOI: 10.1007/s12029-020-00497-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION HCC remains a challenging disease with its unique characteristics and aggressive behavior. Although there are some curative-intent treatments such as liver transplantation and surgical resection, they themselves did not cure the patients with relatively high recurrence rates. Several modalities including local ablation methods like TACE or TARE, systemic treatments such as chemotherapy, tyrosine kinase inhibitors or antiviral therapies are tested in adjuvant or neoadjuvant setting, but none of them offered a survival benefit (except antiviral therapy in HBV-related HCC). CONCLUSION After a decade of plateau in drug development, ICPIs came into podium with their different mechanism of action consistent with immunogenic nature of the disease and with high expectations, and ongoing trials will show if these agents can satisfy unmet demand in this area.
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Affiliation(s)
- Mustafa Dikilitas
- Department of Medical Oncology, Inonu University Liver transplantation İnstitute, Malatya, Turkey.
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19
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 537] [Impact Index Per Article: 134.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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20
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Frankul L, Frenette C. Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy. J Clin Transl Hepatol 2021; 9:220-226. [PMID: 34007804 PMCID: PMC8111105 DOI: 10.14218/jcth.2020.00037] [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: 04/30/2020] [Revised: 10/04/2020] [Accepted: 03/04/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
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Affiliation(s)
| | - Catherine Frenette
- Correspondence to: Catherine Frenette, Scripps Center for Organ Transplant, Scripps Clinic/Green Hospital, 10666 N. Torrey Pines Rd N200, La Jolla, CA 92037, USA. ORCID: https://orcid.org/0000-0002-2245-8173 Tel: +1-858-554-4310, Fax: +1-858-554-3009, E-mail:
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Centonze L, Di Sandro S, Lauterio A, De Carlis R, Frassoni S, Rampoldi A, Tuscano B, Bagnardi V, Vanzulli A, De Carlis L. Surgical Resection vs. Percutaneous Ablation for Single Hepatocellular Carcinoma: Exploring the Impact of Li-RADS Classification on Oncological Outcomes. Cancers (Basel) 2021; 13:1671. [PMID: 33916311 PMCID: PMC8038048 DOI: 10.3390/cancers13071671] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/25/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Background: Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. Methods: We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS) and local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). Results: Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; p = 0.049) and RFS (42.5% vs. 29.8%; p = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; p < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; p = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; p < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; p = 0.035), RFS (45.0% vs. 27.0% RFS; p < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; p < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. Conclusions: Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.
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Affiliation(s)
- Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (S.D.S.); (A.L.); (R.D.C.); (L.D.C.)
| | - Stefano Di Sandro
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (S.D.S.); (A.L.); (R.D.C.); (L.D.C.)
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (S.D.S.); (A.L.); (R.D.C.); (L.D.C.)
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (S.D.S.); (A.L.); (R.D.C.); (L.D.C.)
| | - Samuele Frassoni
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, 20126 Milan, Italy; (S.F.); (V.B.)
| | - Antonio Rampoldi
- Department of Diagnostic and Interventional Radiology, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.R.); (B.T.); (A.V.)
| | - Bruno Tuscano
- Department of Diagnostic and Interventional Radiology, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.R.); (B.T.); (A.V.)
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, 20126 Milan, Italy; (S.F.); (V.B.)
| | - Angelo Vanzulli
- Department of Diagnostic and Interventional Radiology, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (A.R.); (B.T.); (A.V.)
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca’ Granda Hospital, 20162 Milan, Italy; (S.D.S.); (A.L.); (R.D.C.); (L.D.C.)
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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Wang F, Numata K, Takeda A, Ogushi K, Fukuda H, Hara K, Chuma M, Eriguchi T, Tsurugai Y, Maeda S. Safety and efficacy study: Short-term application of radiofrequency ablation and stereotactic body radiotherapy for Barcelona Clinical Liver Cancer stage 0-B1 hepatocellular carcinoma. PLoS One 2021; 16:e0245076. [PMID: 33400718 PMCID: PMC7785216 DOI: 10.1371/journal.pone.0245076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 12/21/2020] [Indexed: 11/19/2022] Open
Abstract
Aim To evaluate the safety and efficacy of the administration of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in the short term to the same patients in Barcelona Clinical Liver Cancer (BCLC) stages 0–B1. Methods From April 2014 to June 2019, we retrospectively reviewed BCLC stage 0–B1 patients with fresh hepatocellular carcinoma (HCC) lesions that were repeatedly treated by RFA (control group, n = 72), and by RFA and subsequent SBRT (case group, n = 26). Propensity score matching (PSM) was performed to reduce the selection bias between two groups. Recurrence, survival, Child–Pugh scores and short-term side effects (fever, bleeding, skin change, abdominal pain and fatigue) were recorded and analyzed. Results After PSM, 21 patients remained in each group. Seventeen and 20 patients in the case and control groups experienced recurrence. For these patients, the median times to progression and follow-up were 10.7 and 35.8 months, respectively. After PSM, the 1-year progression-free survival rate in case and control groups were 66.7% and 52.4%, respectively (P = 0.313). The inter-group overall survival (OS) was comparable (3 and 5-year OS rates in case groups were 87.3% and 74.8%, while rates in control groups were 73.7% and 46.3%, respectively; P = 0.090). The short-term side effects were mild, and the incidence showed no inter-group difference. The 1-year rates of the Child–Pugh score deterioration of ≥2 in case and control groups were 23.8% and 33.3% (P > 0.05), respectively. Conclusion The short-term administration of RFA and SBRT to the same BCLC stage 0–B1 patients may be feasible and effective because of their good prognosis and safety.
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Affiliation(s)
- Feiqian Wang
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
- Ultrasound Department, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
- * E-mail:
| | - Atsuya Takeda
- Radiation Oncology Center, Ofuna Chuo Hospital, Kanagawa, Japan
| | - Katsuaki Ogushi
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Hiroyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Koji Hara
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | | | | | - Shin Maeda
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
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Histological Correlation for Radiofrequency and Microwave Ablation in the Local Control of Hepatocellular Carcinoma (HCC) before Liver Transplantation: A Comprehensive Review. Cancers (Basel) 2020; 13:cancers13010104. [PMID: 33396289 PMCID: PMC7795634 DOI: 10.3390/cancers13010104] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/24/2020] [Accepted: 12/28/2020] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Liver cancer is a growing problem around the world. Drugs for liver cancer have limited effect, there are not enough donors for liver transplants and many patients are not candidates for surgery to remove the tumor. In many of these cases, hyperthermia can destroy the tumor in situ with minimally invasive methods such as radiofrequency or microwave ablation. In this paper we review the literature evaluating success rates for complete ablation as judged by actual examination of treated tumors that were removed when patients received a liver transplant. While notable successes can be achieved with ablation, the published studies indicate both that complete treatment is not as common as thought and that imaging methods such as computed tomography and magnetic resonance scans do not completely identify residual cancer. There is therefore an important opportunity for improvement in the treatment of this disease. Abstract Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely studied and applied ablation techniques for treating primary and secondary liver tumors. These techniques are considered curative for small hepatic tumors, with post-ablation outcomes most commonly assessed by an imaging follow up. However, there is increasing evidence of a discrepancy between radiological and pathological findings when ablated lesions are evaluated following liver resection or liver transplantation. A comprehensive review of the available literature reporting the complete pathological response (cPR) following RFA and MWA was performed to estimate the success rate and identify the factors associated with treatment failure. Following RFA, cPR is reported in 26–96% of tumors compared to 57–95% with MWA. Larger tumor size and vessels larger than 3 mm adjacent to the treated tumor are the most important factors identified by previous studies associated with viable residual tumors after RFA. Correlating post-ablation radiological studies with pathological findings shows that computed tomography (CT) and magnetic resonance imaging (MRI) have low sensitivity but high specificity for detecting residual viable or recurrent hepatocellular carcinoma (HCC) tumors. There are promising recent reports combining multiprobe ablation techniques with three-dimensional treatment planning software and stereotactic-aiming instrumentation to achieve more than 90% cPR in both small and large HCC tumors. In conclusion, the reported success for achieving cPR in HCC following RFA and MWA is highly variable in different studies and decreases with increasing lesion size and unfavorable tumor characteristics. Very few studies have reported a high rate of cPR. As these studies are single-center and retrospective, they need to be further validated and reproduced in other clinical settings.
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Zhang Y, Zhang MW, Fan XX, Mao DF, Ding QH, Zhuang LH, Lv SY. Drug-eluting beads transarterial chemoembolization sequentially combined with radiofrequency ablation in the treatment of untreated and recurrent hepatocellular carcinoma. World J Gastrointest Surg 2020; 12:355-368. [PMID: 32903981 PMCID: PMC7448208 DOI: 10.4240/wjgs.v12.i8.355] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/08/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Drug-eluting beads transarterial chemoem-bolization (DEB-TACE) has the advantages of slow and steady release, high local concentration, and low incidence of adverse drug reactions compared to the traditional TACE. DEB-TACE combined with sequentially ultrasound-guided radiofrequency ablation (RFA) therapy has strong anti-cancer effects and little side effects, but there are fewer related long-term studies until now. AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma (HCC). METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited. Forty patients with untreated HCC were included in Group A, and 36 patients with recurrent HCC were included in Group B. In addition, 40 patients with untreated HCC who were treated with hepatectomy were included in Group C. The serological examination, preoperative magnetic resonance imaging examination, and post-treatment computed tomography enhanced examination were performed for all patients. The efficacy was graded as complete remission (CR), partial remission (PR), stable disease and progressive disease at the 3rd, 6th, and 9th. All patients were followed up for 3 years and their overall survival (OS), disease-free survival (DFS) were assessed. RESULTS The efficacy of Group A and Group C was similar (P > 0.05), but the alanine aminotransferase, aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C (all P < 0.05). The proportions of CR (32.5%), PR (37.5%) were slightly higher than Group A (CR: 27.5%, PR: 35%), but the difference was not statistically significant (χ 2 = 0.701, P = 0.873). No operational-related deaths occurred in Group A and Group C. The OS (97.5%, 84.7%, and 66.1%) and the DFS (75.0%, 51.7%, and 35.4%) of Group A at the 1st, 2nd, and 3rd year after treatment were similar with those of Group C (OS: 90.0%, 79.7%, and 63.8%; DFS: 80.0%, 59.7%, and 48.6%; P > 0.05). The OS rates in Group A and Group B (90%, 82.3%, and 66.4%) were similar (P > 0.05). The DFS rates in Group B (50%, 31.6%, and 17.2%) were lower than that of Group A (P = 0.013). CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy. Patients with recurrent HCC could get a longer survival time through the combined treatment.
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Affiliation(s)
- Yan Zhang
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
| | - Mei-Wu Zhang
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
| | - Xiao-Xiang Fan
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
| | - Da-Feng Mao
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
| | - Quan-Hua Ding
- Department of Gastroenterology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
| | - Lu-Hui Zhuang
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
| | - Shu-Yi Lv
- Department of Interventional Therapy, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang Province, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, Zhejiang Province, China
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Meyer T. Stereotactic body radiotherapy for hepatocellular carcinoma - still searching for a role. J Hepatol 2020; 73:15-16. [PMID: 32386956 DOI: 10.1016/j.jhep.2020.04.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 04/14/2020] [Indexed: 01/15/2023]
Affiliation(s)
- Tim Meyer
- Department of Oncology, UCL Cancer Institute, University College London, London, United Kingdom.
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Satiya J, Schwartz I, Tabibian JH, Kumar V, Girotra M. Ablative therapies for hepatic and biliary tumors: endohepatology coming of age. Transl Gastroenterol Hepatol 2020; 5:15. [PMID: 32258519 PMCID: PMC7063520 DOI: 10.21037/tgh.2019.10.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Ablative therapies refer to minimally invasive procedures performed to destroy abnormal tissue that may arise with many conditions, and can be achieved clinically using chemical, thermal, and other techniques. In this review article, we explore the different ablative therapies used in the management of hepatic and biliary malignancies, namely hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), with a particular focus on radiofrequency ablation (RFA) and photodynamic therapy (PDT) techniques.
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Affiliation(s)
- Jinendra Satiya
- Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, West Palm Beach, FL, USA
| | - Ingrid Schwartz
- Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, FL, USA
| | - James H. Tabibian
- Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Vivek Kumar
- Gastroenterology and Hepatology, UPMC Susquehanna, Williamsport, PA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
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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.
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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
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Kwon J, Chun KS, Song IS, Kim SH, Han S. Long-term outcome of intraoperative radiofrequency ablation for hepatocellular carcinoma and its efficacy as a primary treatment. Ann Hepatobiliary Pancreat Surg 2020; 24:24-32. [PMID: 32181425 PMCID: PMC7061039 DOI: 10.14701/ahbps.2020.24.1.24] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 10/10/2019] [Accepted: 10/23/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUNDS/AIMS We conducted this study to identify long-term outcomes following intraoperative radiofrequency ablation (IO-RFA) for hepatocellular carcinoma (HCC) and to reveal independent prognostic factors for survival. METHODS From December 1998 to February 2019, 183 patients underwent IO-RFA for HCC. These patients were divided into two groups according to whether RFA was done as a first-line (1-RFA group, n=106) or secondary-line (2-RFA group, n=77) treatment. Furthermore, we compared the survival outcomes between the 1-RFA and 2-RFA groups. RESULTS There were no significant differences in type of surgical approaches between the two groups (p=0.079). The number of tumors and largest tumor size were not significantly different between the two groups. Overall recurrence rate was 53%, and the 2-RFA group showed a higher recurrence rate (46.2% in 1-RFA group versus 62.3% in 2-RFA group; p=0.031). The 5-year overall survival (OS) and disease-free survival (DFS) rates of all the patients were 75.2% and 27.9%, respectively. The OS and DFS rates were significantly higher in the 1-RFA group. The 5-year OS rates were 83.6% and 64.9% in the 1-RFA and 2-RFA groups, respectively (p=0.010), whereas the 5-year DFS rates were 32.2% and 21.6%, respectively (p=0.012). On multivariate analysis, HBV-LC, 2-RFA, recurrence, and postoperative complications were independent predictive factors for survival. CONCLUSIONS Therapeutic outcomes of IO-RFA were comparable to those of surgical resection. Additionally, 1-RFA might be an alternative treatment for naïve HCC in patients with uncompensated liver function and severe comorbidities.
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Affiliation(s)
- Jongduk Kwon
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Kwang-Sik Chun
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - In-Sang Song
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Seok-Hwan Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
| | - Sunjong Han
- Department of Surgery, Chungnam National University Hospital, Daejeon, Korea
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Devcic Z, Elboraey M, Vidal L, Mody K, Harnois D, Patel T, Toskich BB. Individualized Ablation of Hepatocellular Carcinoma: Tailored Approaches across the Phenotype Spectrum. Semin Intervent Radiol 2019; 36:287-297. [PMID: 31680719 DOI: 10.1055/s-0039-1698755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ablation is now recommended by international guidelines for the definitive treatment of hepatocellular carcinoma (HCC). Extensive clinical studies have demonstrated outcomes comparable to surgical resection with shorter hospital stays, decreased costs, and improved quality of life. Successful ablation requires complete treatment of both tumor and margin while preserving critical adjacent structures. HCC exhibits highly variable presentations in both anatomic involvement and biology which have significant implications on choice of ablative therapy. There are now abundant ablation modalities and adjunctive techniques which can be used to individualize ablation and maximize curative results. This article provides a patient-centered summary of approaches to HCC ablation in the context of patient performance, hepatic reserve, tumor phenotype and biology, intra- and extrahepatic anatomy, and ablation technology.
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Affiliation(s)
- Zlatko Devcic
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
| | - Mohamed Elboraey
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
| | - Lucas Vidal
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Kabir Mody
- Division of Oncology, Mayo Clinic Florida, Jacksonville, Florida
| | - Denise Harnois
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Tushar Patel
- Department of Transplantation, Mayo Clinic Florida, Jacksonville, Florida
| | - Beau B Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, Florida
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Bale R, Schullian P, Eberle G, Putzer D, Zoller H, Schneeberger S, Manzl C, Moser P, Oberhuber G. Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers. Hepatology 2019; 70:840-850. [PMID: 30520063 PMCID: PMC6766867 DOI: 10.1002/hep.30406] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 11/25/2018] [Indexed: 12/23/2022]
Abstract
This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0-71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1-8) and 2.5 cm (range, 1-8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.
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Affiliation(s)
- Reto Bale
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Peter Schullian
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Gernot Eberle
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Daniel Putzer
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Heinz Zoller
- Departments of Medicine II Gastroenterology and HepatologyMedical University InnsbruckInnsbruckAustria
| | | | - Claudia Manzl
- PathologyMedical University InnsbruckInnsbruckAustria
| | - Patrizia Moser
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
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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.
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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
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Santopaolo F, Lenci I, Milana M, Manzia TM, Baiocchi L. Liver transplantation for hepatocellular carcinoma: Where do we stand? World J Gastroenterol 2019; 25:2591-2602. [PMID: 31210712 PMCID: PMC6558441 DOI: 10.3748/wjg.v25.i21.2591] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
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Affiliation(s)
- Francesco Santopaolo
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Tommaso Maria Manzia
- Transplant Surgery Unit, Department of Surgery, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
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Gans JH, Lipman J, Golowa Y, Kinkhabwala M, Kaubisch A. Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in? Semin Nucl Med 2019; 49:170-181. [DOI: 10.1053/j.semnuclmed.2019.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Serra C, Cucchetti A, Felicani C, Mosconi C, De Cinque A, Golfieri R, Andreone P, Ercolani G, Maroni L, Ravaioli M, D'Errico A, Pinna AD, Cescon M. Assessment of Radiofrequency Ablation Efficacy for Hepatocellular Carcinoma by Histology and Pretransplant Radiology. Liver Transpl 2019; 25:88-97. [PMID: 30415500 DOI: 10.1002/lt.25381] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 10/19/2018] [Indexed: 12/12/2022]
Abstract
Radiofrequency ablation (RFA) represents a potentially curative option for early-stage hepatocellular carcinoma (HCC). This study aims at evaluating the histologic response after RFA of small HCCs arising in cirrhosis. Data were reviewed from 78 patients with de novo HCCs who were treated with RFA and subsequently transplanted. The last radiological assessment before liver transplantation (LT) was used for comparison between modified Response Evaluation Criteria in Solid Tumors (mRECIST) and histological findings. A total of 125 de novo HCCs (median diameter, 20 mm) were treated with RFA only in 92 sessions. There were 98 nodules that did not show local recurrence during follow-up (78.4%), and the remaining were retreated, except 1 because of subsequent LT. On explanted livers, complete pathological response (CPR) was observed in 61.6%, being 76.9% when <2 cm, 55.0% when 2-3 cm, and 30.8% when >3 cm. Tumors near hepatic vessels had CPR in 50% of patients versus 69.3% for tumors distant from vessels (P = 0.039). Of the 125 HCCs, 114 had available radiological assessment within a median of 3 months before LT. Complete radiological response, according to mRECIST, was observed in 77.2% of nodules before LT. The Cohen κ was 0.48 (moderate agreement). The overall accuracy was 78.1%. A total of 18 complications were recorded with only 1 graded as major. In conclusion, RFA can provide high CPR for HCC, especially in smaller tumors distant from hepatic veins or portal branches. The agreement between mRECIST and histology is only moderate. Further refinements in radiological assessment are essential to accurately assess the true effectiveness of RFA.
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Affiliation(s)
- Carla Serra
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Cristina Felicani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Cristina Mosconi
- Radiology Unit, Department of Diagnostic Medicine and Prevention, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Antonio De Cinque
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic Medicine and Prevention, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Lorenzo Maroni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Matteo Ravaioli
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Antonia D'Errico
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - Antonio Daniele Pinna
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Abstract
Hepatocellular carcinoma (HCC) in proximity to major hepatic vasculature poses a risk for invasion, which would contraindicate liver transplantation, yet, is difficult to treat with thermal ablation. This study was undertaken to evaluate the feasibility of irreversible electroporation (IRE) as a bridge to transplantation for high-risk tumors. All patients with HCC in proximity to major hepatic vasculature treated with laparoscopic IRE as bridge to transplantation were studied. Patient and tumor characteristics, length of stay, and treatment-related complications were recorded. Tumor response was assessed with CT and explant pathology. Five patients with a median Model for End Stage Liver Disease (MELD) of 13 (7–21) underwent IRE. The median tumor size was 2.7 cm (1.5–3.7 cm). Adjacent structures included the right portal vein, hepatic veins/inferior vena cava (IVC) and left portal vein. Length of stay was one day for all patients. One patient suffered portal vein thrombosis. The transplant occurred at a median of 142 days (47–264) after IRE. Pathologic necrosis ranged from 30 to 100 per cent, without any vascular invasion. Four patients remain alive with no evidence of disease with median follow-up of 403 (227–623) days. The remaining patients died because of transplant-related complications onpost IRE day 297. IRE shows promise as a bridge to liver transplant for high risk HCC in a preliminary series, justifying further prospective evaluation.
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Affiliation(s)
- Robert M. Cannon
- Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville, Louisville, Kentucky; Departments of
| | | | - Jared A. White
- Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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Au KP, Chok KSH. Multidisciplinary approach for post-liver transplant recurrence of hepatocellular carcinoma: A proposed management algorithm. World J Gastroenterol 2018; 24:5081-5094. [PMID: 30568386 PMCID: PMC6288653 DOI: 10.3748/wjg.v24.i45.5081] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 10/21/2018] [Accepted: 11/07/2018] [Indexed: 02/06/2023] Open
Abstract
A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy (SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligo-recurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a pre-requisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.
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Affiliation(s)
- Kin Pan Au
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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陈 书, 王 宏, 张 文, 陈 继, 卢 鹏. [Clinical application of laparoscopy-assisted and percutaneous radiofrequency ablation for hepatocellular carcinoma]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2018; 38:1147-1150. [PMID: 30377101 PMCID: PMC6744195 DOI: 10.12122/j.issn.1673-4254.2018.09.21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compared the efficacy of laparoscopy- assisted radiofrequency ablation (LRFA) and percutaneous radiofrequency ablation (PRFA) for the treatment of hepatocellular carcinoma (HCC). METHODS Between September, 2013 and September, 2016, a total of 60 HCC patients with 78 tumor nodules underwent LRFA (30 cases with 46 tumor nodules) and PRFA (30 cases with 32 tumor nodules) in our hospital. The patients were followed up for 3 years to compare the complete ablation rate, serious complications, recurrence rate and long-term survival rate between the two groups. RESULTS The patients receiving LRFA had a complete ablation rate of 95.65% (44/46), significantly higher than the rate of 93.75% (30/32) in PRFA group (P > 0.05). Significant differences were found between LRFA and PRFA groups in the incidence of serious complications [0 vs 6.7% (2/30), P < 0.05] and recurrence rate [13.33% (4/30) vs 23.33% (7/30), P < 0.05]. The 1-and 3-year overall survival rates of the patients were 96.15% and 55.12% in LRFA group and 93.73% and 48.54% in PRFA group, respectively (P > 0.05). CONCLUSIONS Both LRFA and PRFA are effective for HCC treatment, but is associated with a lower recurrence rate, fewer serious complications, a better treatment safety and a better applicability for tumor in difficult locations.
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Affiliation(s)
- 书德 陈
- />解放军总医院海南分院肝胆外科，海南 三亚 572000Department of Hepatobiliary Surgery, Affiliated Hainan Hospital of General Hospital of PLA, Sanya 572000, China
| | - 宏光 王
- />解放军总医院海南分院肝胆外科，海南 三亚 572000Department of Hepatobiliary Surgery, Affiliated Hainan Hospital of General Hospital of PLA, Sanya 572000, China
| | - 文智 张
- />解放军总医院海南分院肝胆外科，海南 三亚 572000Department of Hepatobiliary Surgery, Affiliated Hainan Hospital of General Hospital of PLA, Sanya 572000, China
| | - 继业 陈
- />解放军总医院海南分院肝胆外科，海南 三亚 572000Department of Hepatobiliary Surgery, Affiliated Hainan Hospital of General Hospital of PLA, Sanya 572000, China
| | - 鹏 卢
- />解放军总医院海南分院肝胆外科，海南 三亚 572000Department of Hepatobiliary Surgery, Affiliated Hainan Hospital of General Hospital of PLA, Sanya 572000, China
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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Nault JC, Sutter O, Nahon P, Ganne-Carrié N, Séror O. Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. J Hepatol 2018; 68:783-797. [PMID: 29031662 DOI: 10.1016/j.jhep.2017.10.004] [Citation(s) in RCA: 275] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 10/01/2017] [Accepted: 10/06/2017] [Indexed: 02/06/2023]
Abstract
Percutaneous treatment of hepatocellular carcinoma (HCC) encompasses a vast range of techniques, including monopolar radiofrequency ablation (RFA), multibipolar RFA, microwave ablation, cryoablation and irreversible electroporation. RFA is considered one of the main curative treatments for HCC of less than 5 cm developing on cirrhotic liver, together with surgical resection and liver transplantation. However, controversies exist concerning the respective roles of ablation and liver resection for HCC of less than 3 to 5 cm on cirrhotic liver. In line with the therapeutic algorithm of early HCC, percutaneous ablation could also be used as a bridge to liver transplantation or in a sequence of upfront percutaneous treatment, followed by transplantation if the patient relapses. Moreover, several innovations in ablation methods may help to efficiently treat early HCC, initially considered as "non-ablatable", and might, in some cases, extend ablation criteria beyond early HCC, enabling treatment of more patients with a curative approach.
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Affiliation(s)
- Jean-Charles Nault
- Liver Unit, 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
- Department of Radiology, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
| | - Pierre Nahon
- Liver Unit, 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
- Liver Unit, 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 Séror
- 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; Department of Radiology, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France.
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Coletta M, Nicolini D, Benedetti Cacciaguerra A, Mazzocato S, Rossi R, Vivarelli M. Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same? Transl Gastroenterol Hepatol 2017; 2:78. [PMID: 29034351 PMCID: PMC5639014 DOI: 10.21037/tgh.2017.09.01] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 08/28/2017] [Indexed: 12/13/2022] Open
Abstract
Liver transplant (LT) is considered the best curative treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. The possibility to perform LT in HCC patients is limited by the liver grafts supply; indeed, the shortage of donors often leads to a long time on waiting list and then to dropout because of tumor progression. Bridging therapies are neo-adjuvant treatments given to patients on LT waitlist, with the aim to prevent tumor progression and to reduce dropout rate. Many bridging modalities have been proposed. The choice of each treatment is based on the characteristics of the patient, liver function, comorbidities and on the number, dimensions and localization of HCC. This review article describes several types of bridging therapies, focusing on the indications for different kind of patients.
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Affiliation(s)
- Martina Coletta
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Daniele Nicolini
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Andrea Benedetti Cacciaguerra
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Susanna Mazzocato
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Roberta Rossi
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Marco Vivarelli
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
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Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium. Ann Surg 2017; 266:525-535. [PMID: 28654545 DOI: 10.1097/sla.0000000000002381] [Citation(s) in RCA: 137] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013). RESULTS Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044). CONCLUSIONS Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.
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Györi GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg 2017; 49:236-243. [PMID: 29104589 PMCID: PMC5653748 DOI: 10.1007/s10353-017-0487-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 07/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1‑, 3‑, 5‑year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.
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Affiliation(s)
- Georg P. Györi
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - D. Moritz Felsenreich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gerd R. Silberhumer
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Thomas Soliman
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gabriela A. Berlakovich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
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Kollmann D, Selzner N, Selzner M. Bridging to liver transplantation in HCC patients. Langenbecks Arch Surg 2017; 402:863-871. [PMID: 28755240 DOI: 10.1007/s00423-017-1609-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/19/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver transplantation (LT) is the only cure for patients diagnosed with unresectable hepatocellular carcinoma (HCC), and HCC has become the leading indication for LT in the USA. The shortage of liver grafts results in a significant waiting time for LT with the risk of tumour progression. Treating HCCs during the waiting time prior to transplantation (bridging therapy) is an attractive strategy to reduce the risk of exceeding the tumour criteria for transplantation. Studies on bridging therapy are heterogenous and due to ethical issues, mostly of retrospective design. PURPOSE We summarize the main studies and methods that have been reported on bridging therapies for patients with HCC waiting for a LT. CONCLUSION During the waiting period for LT, patients with HCC at risk for tumour progression and therefore bridging therapy is recommended for patients with an estimated waiting time of ≥6 months. Bridging therapy for patients with HCC prior to LT mainly include locoregional therapies (LRTs), with transarterial chemoembolization (TACE) being the most common, followed by radio frequency ablation (RFA). Because of a continuous enhancement of therapy options, including a more precise adjustment of external radiotherapy, further possibilities for an individualized bridging therapy for patients with HCC have been developed. Patients with compensated liver cirrhosis and small tumour size are preferably treated with RFA, whereas patients with larger tumour size but compensated liver function are treated with TACE/TARE. Patients with uncompensated liver cirrhosis and larger tumour size can nowadays be successfully bridged to LT with external radiotherapy without increasing the risk for further deterioration of liver function.
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Affiliation(s)
- Dagmar Kollmann
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Nazia Selzner
- Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Markus Selzner
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada. .,General Surgery and Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, 585 University Avenue, 11 PMB 178, Toronto, ON, M5G 2N2, Canada.
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Lee MW, Raman SS, Asvadi NH, Siripongsakun S, Hicks RM, Chen J, Worakitsitisatorn A, McWilliams J, Tong MJ, Finn RS, Agopian VG, Busuttil RW, Lu DSK. Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis. Hepatology 2017; 65:1979-1990. [PMID: 28170115 DOI: 10.1002/hep.29098] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 01/26/2017] [Accepted: 01/30/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).
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Affiliation(s)
- Min Woo Lee
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Steven S Raman
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Nazanin H Asvadi
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Surachate Siripongsakun
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology, Chulabhorn Hospital, Bangkok, Thailand
| | - Robert M Hicks
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Jeffrey Chen
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Akeanong Worakitsitisatorn
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA.,Department of Radiology, Chulabhorn Hospital, Bangkok, Thailand
| | - Justin McWilliams
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
| | - Myron J Tong
- Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Richard S Finn
- Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Vatche G Agopian
- Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, Los Angeles, CA
| | - Ronald W Busuttil
- Department of Surgery, Dumont-UCLA Transplant and Liver Cancer Centers, Los Angeles, CA
| | - David S K Lu
- Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA
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Treatment Options in Patients Awaiting Liver Transplantation with Hepatocellular Carcinoma and Cholangiocarcinoma. Clin Liver Dis 2017; 21:231-251. [PMID: 28364811 DOI: 10.1016/j.cld.2016.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) provides a good chance of cure for selected patients with hepatocellular carcinoma (HCC) and perihilar cholangiocarcinoma (pCCA). Patients with HCC on a waiting list for LT are at risk for tumor progression and dropout. Treatment of HCC with locoregional therapies may lessen dropout due to tumor progression. Strict selection and adherence to the LT criteria for patients with pCCA before and after neoadjuvant chemotherapy are critical for optimal outcome with LT. This article reviews the existing data for the various treatment strategies used for patients with HCC and pCCA awaiting LT.
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Pollom EL, Lee K, Durkee BY, Grade M, Mokhtari DA, Wahl DR, Feng M, Kothary N, Koong AC, Owens DK, Goldhaber-Fiebert J, Chang DT. Cost-effectiveness of Stereotactic Body Radiation Therapy versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Markov Modeling Study. Radiology 2017; 283:460-468. [PMID: 28045603 PMCID: PMC5410949 DOI: 10.1148/radiol.2016161509] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. © RSNA, 2017 Online supplemental material is available for this article.
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Affiliation(s)
- Erqi L. Pollom
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Kyueun Lee
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Ben Y. Durkee
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Madeline Grade
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Daniel A. Mokhtari
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Daniel R. Wahl
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Mary Feng
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Nishita Kothary
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Albert C. Koong
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Douglas K. Owens
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Jeremy Goldhaber-Fiebert
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
| | - Daniel T. Chang
- From the Department of Radiation Oncology (E.L.P., B.Y.D., M.G., D.A.M., A.C.K., D.T.C.), Centers for Health Policy and Primary Care and Outcomes Research (K.L., D.K.O., J.G.F.), and Department of Radiology (N.K.), Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5847; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Mich (D.R.W., M.F.); and Veteterans Affairs Palo Alto Health Care System, Palo Alto, Calif (D.K.O.)
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Mannina EM, Cardenes HR, Lasley FD, Goodman B, Zook J, Althouse S, Cox JA, Saxena R, Tector J, Maluccio M. Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes. Int J Radiat Oncol Biol Phys 2017; 97:931-938. [DOI: 10.1016/j.ijrobp.2016.12.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/17/2016] [Accepted: 12/28/2016] [Indexed: 12/13/2022]
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Zimmerman A, Grand D, Charpentier KP. Irreversible electroporation of hepatocellular carcinoma: patient selection and perspectives. J Hepatocell Carcinoma 2017; 4:49-58. [PMID: 28331845 PMCID: PMC5357069 DOI: 10.2147/jhc.s129063] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Irreversible electroporation (IRE) is a novel form of tissue ablation that uses high-current electrical pulses to induce pore formation of the cell lipid bilayer, leading to cell death. The safety of IRE for ablation of hepatocellular carcinoma (HCC) has been established. Outcome data for ablation of HCC by IRE are limited, but early results are encouraging and suggest equivalency to the outcomes obtained for thermal ablation for appropriately selected, small (<3 cm) tumors. Long-term oncologic efficacy and histopathologic response data have not been published, and therefore, application of IRE for the treatment of HCC should still be viewed with caution.
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Affiliation(s)
| | - David Grand
- Department of Radiology, Rhode Island Hospital, Brown University, Providence, RI, USA
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