Digestive Disease Interventions
DOI: 10.1055/s-0044-1791837
Review Article

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

Juana V. Barrera
1   Interventional Radiology Department, School of Medicine, University of California San Francisco, San Francisco, California
,
Leonard Dallag
2   Interventional Radiology Department, University of Miami, Miami, Florida
,
Rubeel Akram
3   Interventional Radiology Department, UT Southwestern Medical Center, Dallas, Texas
,
Jason Salsamendi
4   Interventional Radiology Department, City of Hope, Los Angeles, California
,
5   Interventional Radiology Department, University of Toronto, Toronto, Canada
,
Chase J. Wehrle
6   Interventional Radiology Department, Cleveland Clinic, Cleveland, Ohio
,
Jamaal Benjamin
3   Interventional Radiology Department, UT Southwestern Medical Center, Dallas, Texas
,
Maria del Pilar Bayona Molano
2   Interventional Radiology Department, University of Miami, Miami, Florida
› Author Affiliations
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Abstract

Hepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Ethical Approval and Consent to Participate

This review did not require institutional review board's approval. The research satisfied all three requirements for a waiver of authorization under 45 Code of Federal Regulations 164.512.


Consent for Publication

Not applicable.


Availability of Data and Materials

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on a reasonable request.


Competing Interests

The authors have no relevant financial or nonfinancial interests to disclose.


Preprint Publication

Not applicable.


Authorship

J.V.B., L.D., R.A., J.S., C.B., C.J.W., and M.P.B.M. contributed to the conception and design of the work, acquisition, and interpretation of data, and substantively revised the work. In addition, J.V.B. contributed with the edition and grammar style. L.D., J.S., and C.J.W. made contributions to the conception of the work. R.A. with data collection, M.P.B.M. made contributions with revision and approval of the work. All authors read and approved the final manuscript.




Publication History

Received: 21 September 2024

Accepted: 25 September 2024

Article published online:
21 October 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 
  • References

  • 1 Singal AG, Kanwal F, Llovet JM. Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy. Nat Rev Clin Oncol 2023; 20 (12) 864-884
  • 2 Reig M, Forner A, Rimola J. et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 2022; 76 (03) 681-693
  • 3 Mehta N. Liver transplantation criteria for hepatocellular carcinoma, including posttransplant management. Clin Liver Dis (Hoboken) 2021; 17 (05) 332-336
  • 4 Schoenberger H, Rich NE, Jones P, Yekkaluri S, Yopp A, Singal AG. Multi-Ethnic HCC Cohort Investigators. Racial and ethnic disparities in barriers to care in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol 2023; 21 (04) 1094-1096.e2
  • 5 Siddique O, Yoo ER, Perumpail RB. et al. The importance of a multidisciplinary approach to hepatocellular carcinoma. J Multidiscip Healthc 2017; 10: 95-100
  • 6 Seif El Dahan K, Reczek A, Daher D. et al. Multidisciplinary care for patients with HCC: a systematic review and meta-analysis. Hepatol Commun 2023; 7 (05) e0143
  • 7 Park JW, Chen M, Colombo M. et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int 2015; 35 (09) 2155-2166
  • 8 Salem R, Johnson GE, Kim E. et al. Yttrium-90 radioembolization for the treatment of solitary, unresectable HCC: the LEGACY Study. Hepatology 2021; 74 (05) 2342-2352
  • 9 Goyal P, Salem R, Mouli SK. Role of interventional oncology in hepatocellular carcinoma: future best practice beyond current guidelines. Br J Radiol 2022; 95 (1138): 20220379
  • 10 Shiina S, Tateishi R, Imamura M. et al. Percutaneous ethanol injection for hepatocellular carcinoma: 20-year outcome and prognostic factors. Liver Int 2012; 32 (09) 1434-1442
  • 11 Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210 (03) 655-661
  • 12 Gervais DA, Arellano RS. Percutaneous tumor ablation for hepatocellular carcinoma. AJR Am J Roentgenol 2011; 197 (04) 789-794
  • 13 Yang P, Li N. Efficacy of percutaneous ethanol injection versus radiofrequency ablation for single hepatocellular carcinoma no larger than 5 cm. J Int Med Res 2022; 50 (07) 3000605221111281
  • 14 Lu DE, Cheng SW, Lin YS. et al. Combination of radiofrequency ablation and percutaneous ethanol injection versus radiofrequency ablation alone for hepatocellular carcinoma: a systematic review and meta-analysis. Ann Hepatol 2022; 27 (05) 100729
  • 15 Crocetti L, Bozzi E, Scalise P. et al. Locoregional treatments for bridging and downstaging HCC to liver transplantation. Cancers (Basel) 2021; 13 (21) 5558
  • 16 Doyle A, Gorgen A, Muaddi H. et al. Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients. J Hepatol 2019; 70 (05) 866-873
  • 17 Deng Q, He M, Fu C, Feng K, Ma K, Zhang L. Radiofrequency ablation in the treatment of hepatocellular carcinoma. Int J Hyperthermia 2022; 39 (01) 1052-1063
  • 18 Pompili M, Mirante VG, Rondinara G. et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl 2005; 11 (09) 1117-1126
  • 19 Lu DSK, Yu NC, Raman SS. et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology 2005; 41 (05) 1130-1137
  • 20 Ohmoto K, Yoshioka N, Tomiyama Y. et al. Comparison of therapeutic effects between radiofrequency ablation and percutaneous microwave coagulation therapy for small hepatocellular carcinomas. J Gastroenterol Hepatol 2009; 24 (02) 223-227
  • 21 Liang P, Wang Y. Microwave ablation of hepatocellular carcinoma. Oncology 2007; 72 (Suppl. 01) 124-131
  • 22 Poggi G, Tosoratti N, Montagna B, Picchi C. Microwave ablation of hepatocellular carcinoma. World J Hepatol 2015; 7 (25) 2578-2589
  • 23 Sommer CM, Sommer SA, Mokry T. et al. Quantification of tissue shrinkage and dehydration caused by microwave ablation: experimental study in kidneys for the estimation of effective coagulation volume. J Vasc Interv Radiol 2013; 24 (08) 1241-1248
  • 24 Som A, Reid NJ, DiCapua J. et al. Microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant: a single center experience. Cardiovasc Intervent Radiol 2021; 44 (11) 1749-1754
  • 25 Wang T, Zhang XY, Lu X, Zhai B. Laparoscopic microwave ablation of hepatocellular carcinoma at liver surface: technique effectiveness and long-term outcomes. Technol Cancer Res Treat 2019; 18: 1533033818824338
  • 26 Couillard AB, Knott EA, Zlevor AM. et al. Microwave ablation as bridging to liver transplant for patients with hepatocellular carcinoma: a single-center retrospective analysis. J Vasc Interv Radiol 2022; 33 (09) 1045-1053
  • 27 Perry RH, Green DW. Perry's Chemical Engineers' Handbook. McGraw-Hill; 1984
  • 28 Song KD. Percutaneous cryoablation for hepatocellular carcinoma. Clin Mol Hepatol 2016; 22 (04) 509-515
  • 29 Hu KQ. Advances in clinical application of cryoablation therapy for hepatocellular carcinoma and metastatic liver tumor. J Clin Gastroenterol 2014; 48 (10) 830-836
  • 30 Gilbert JC, Onik GM, Hoddick WK, Rubinsky B. Real time ultrasonic monitoring of hepatic cryosurgery. Cryobiology 1985; 22 (04) 319-330
  • 31 Tacke J, Adam G, Haage P, Sellhaus B, Grosskortenhaus S, Günther RW. MR-guided percutaneous cryotherapy of the liver: in vivo evaluation with histologic correlation in an animal model. J Magn Reson Imaging 2001; 13 (01) 50-56
  • 32 Rong G, Bai W, Dong Z. et al. Long-term outcomes of percutaneous cryoablation for patients with hepatocellular carcinoma within Milan criteria. PLoS One 2015; 10 (04) e0123065
  • 33 Niu LZ, Li JL, Xu KC. Percutaneous cryoablation for liver cancer. J Clin Transl Hepatol 2014; 2 (03) 182-188
  • 34 Shafir M, Shapiro R, Sung M, Warner R, Sicular A, Klipfel A. Cryoablation of unresectable malignant liver tumors. Am J Surg 1996; 171 (01) 27-31
  • 35 Pearson AS, Izzo F, Fleming RY. et al. Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies. Am J Surg 1999; 178 (06) 592-599
  • 36 Yang Y, Wang C, Lu Y. et al. Outcomes of ultrasound-guided percutaneous argon-helium cryoablation of hepatocellular carcinoma. J Hepatobiliary Pancreat Sci 2012; 19 (06) 674-684
  • 37 Kinsey E, Lee HM. Management of hepatocellular carcinoma in 2024: the multidisciplinary paradigm in an evolving treatment landscape. Cancers (Basel) 2024; 16 (03) 666
  • 38 Brown KT, Do RK, Gonen M. et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol 2016; 34 (17) 2046-2053
  • 39 Cesario S, Genovesi V, Salani F. et al. Evolving landscape in liver transplantation for hepatocellular carcinoma: from stage migration to immunotherapy revolution. Life (Basel) 2023; 13 (07) 1562
  • 40 Zhong BY, Jin ZC, Chen JJ, Zhu HD, Zhu XL. Role of transarterial chemoembolization in the treatment of hepatocellular carcinoma. J Clin Transl Hepatol 2023; 11 (02) 480-489
  • 41 Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent updates of transarterial chemoembolization in hepatocellular carcinoma. Int J Mol Sci 2020; 21 (21) 8165
  • 42 Millonig G, Graziadei IW, Freund MC. et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2007; 13 (02) 272-279
  • 43 Xu L, Chen L, Zhang W. Neoadjuvant treatment strategies for hepatocellular carcinoma. World J Gastrointest Surg 2021; 13 (12) 1550-1566
  • 44 Sacco R, Conte C, Tumino E. et al. Transarterial radioembolization for hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016; 3: 25-29
  • 45 National Comprehensive Cancer Network (NCCN) [webpage on the Internet] National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. 2010. Hepatobiliary Guidelines. V2. Accessed December 30, 2015 at: http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf
  • 46 Thomas MB, Jaffe D, Choti MM. et al. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2010; 28 (25) 3994-4005
  • 47 Al-Kalbani A, Kamel Y. Y-90 microspheres in the treatment of unresectable hepatocellular carcinoma. Saudi J Gastroenterol 2008; 14 (02) 90-92
  • 48 Kulik LM, Mulcahy MF, Omary RA, Salem R. Emerging approaches in hepatocellular carcinoma. J Clin Gastroenterol 2007; 41 (09) 839-854
  • 49 Labgaa I, Tabrizian P, Titano J. et al. Feasibility and safety of liver transplantation or resection after transarterial radioembolization with yttrium-90 for unresectable hepatocellular carcinoma. HPB (Oxford) 2019; 21 (11) 1497-1504
  • 50 Gaba RC, Lewandowski RJ, Kulik LM. et al. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol 2009; 16 (06) 1587-1596
  • 51 Gabr A, Kulik L, Mouli S. et al. Liver transplantation following yttrium-90 radioembolization: 15-year experience in 207-patient cohort. Hepatology 2021; 73 (03) 998-1010
  • 52 Serenari M, Cappelli A, Cucchetti A. et al. Deceased donor liver transplantation after radioembolization for hepatocellular carcinoma and portal vein tumoral thrombosis: a pilot study. Liver Transpl 2021; 27 (12) 1758-1766
  • 53 Lopez-Lopez V, Miura K, Kuemmerli C. et al. Selecting the appropriate downstaging and bridging therapies for hepatocellular carcinoma: What is the role of transarterial radioembolization? A pooled analysis. Cancers (Basel) 2023; 15 (07) 2122
  • 54 Salem R, Lewandowski RJ, Mulcahy MF. et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010; 138 (01) 52-64
  • 55 Ricke J, Bulla K, Kolligs F. et al; SORAMIC Study Group. Safety and toxicity of radioembolization plus sorafenib in advanced hepatocellular carcinoma: analysis of the European multicentre trial SORAMIC. Liver Int 2015; 35 (02) 620-626
  • 56 Kim E, Sher A, Abboud G. et al. Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study. Lancet Gastroenterol Hepatol 2022; 7 (09) 843-850
  • 57 Garin E, Tselikas L, Guiu B. et al; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol 2021; 6 (01) 17-29
  • 58 Riaz A, Awais R, Salem R. Side effects of yttrium-90 radioembolization. Front Oncol 2014; 4: 198
  • 59 Lencioni R, Llovet JM, Han G. et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. J Hepatol 2016; 64 (05) 1090-1098
  • 60 Meyer T, Fox R, Ma YT. et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2017; 2 (08) 565-575
  • 61 Kudo M, Han G, Finn RS. et al. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase III trial. Hepatology 2014; 60 (05) 1697-1707
  • 62 Kudo M, Cheng A-L, Park J-W. et al. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol 2018; 3 (01) 37-46
  • 63 Kennedy AS, Nutting C, Coldwell D, Gaiser J, Drachenberg C. Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys 2004; 60 (05) 1552-1563
  • 64 Wang H, Liu Y, Shen K. et al. A comparison between radiofrequency ablation combined with transarterial chemoembolization and surgical resection in hepatic carcinoma: a meta-analysis. J Cancer Res Ther 2019; 15 (07) 1617-1623
  • 65 Wong TC, Chiang C-L, Lee A-S. et al. Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: a propensity score matched analysis. Surg Oncol 2019; 28: 228-235
  • 66 Shen XW, Feng J, Sun XG. Argon-helium cryosurgery combined with transcatheter arterial chemoembolization for treatment of liver metastatic tumors: an analysis of therapeutic results. Jie Ru Fang She Xue Za Zhi 2010; 19: 35-37
  • 67 Bai GD, Lian ZP, Huang DP. Cryoablation combined with chemotherapy in the treatment of advanced primary liver cancer. Dang Dai Yi Xue 2010; 16: 293-295
  • 68 Xu KC, Niu LZ, He WB, Guo ZQ, Hu YZ, Zuo JS. Percutaneous cryoablation in combination with ethanol injection for unresectable hepatocellular carcinoma. World J Gastroenterol 2003; 9 (12) 2686-2689
  • 69 Ricke J, Klümpen HJ, Amthauer H. et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. J Hepatol 2019; 71 (06) 1164-1174
  • 70 Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 2009; 461 (7267): 1071-1078
  • 71 Kouloulias V, Mosa E, Georgakopoulos J. et al. Three-dimensional conformal radiotherapy for hepatocellular carcinoma in patients unfit for resection, ablation, or chemotherapy: a retrospective study. ScientificWorldJournal 2013; 2013: 780141
  • 72 Mazzaferro V, Regalia E, Doci R. et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334 (11) 693-699
  • 73 Yao FY, Ferrell L, Bass NM. et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33 (06) 1394-1403
  • 74 Mazzaferro V, Llovet JM, Miceli R. et al; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10 (01) 35-43
  • 75 Shimamura T, Akamatsu N, Fujiyoshi M. et al; Japanese Liver Transplantation Society. Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study. Transpl Int 2019; 32 (04) 356-368
  • 76 Sasaki K, Firl DJ, Hashimoto K. et al. Development and validation of the HALT-HCC score to predict mortality in liver transplant recipients with hepatocellular carcinoma: a retrospective cohort analysis. Lancet Gastroenterol Hepatol 2017; 2 (08) 595-603
  • 77 Mazzaferro V, Sposito C, Zhou J. et al. Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma. Gastroenterology 2018; 154 (01) 128-139
  • 78 Wehrle CJ, Kusakabe J, Akabane M. et al. Expanding selection criteria in deceased donor liver transplantation for hepatocellular carcinoma: long-term follow-up of a national registry and 2 transplant centers. Transplantation 2024;
  • 79 Wehrle CJ, Fujiki M, Schlegel A. et al. Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: a novel pre-transplant protocol. Liver Transpl 2024;
  • 80 Wehrle CJ, Hong H, Kamath S. et al. Tumor mutational burden from circulating tumor DNA predicts recurrence of hepatocellular carcinoma after resection: an emerging biomarker for surveillance. Ann Surg 2024; 280 (03) 504-513
  • 81 Wehrle CJ, Raj R, Aykun N. et al. Liquid biopsy by ctDNA in liver transplantation for colorectal cancer liver metastasis. J Gastrointest Surg 2023; 27 (07) 1498-1509
  • 82 Wehrle CJ, Raj R, Aykun N. et al. Circulating tumor DNA in colorectal cancer liver metastasis: analysis of patients receiving liver resection and transplant. JCO Clin Cancer Inform 2023; 7: e2300111
  • 83 Roberts JP, Venook A, Kerlan R, Yao F. Hepatocellular carcinoma: ablate and wait versus rapid transplantation. Liver Transpl 2010; 16 (08) 925-929
  • 84 Cescon M, Cucchetti A, Ravaioli M, Pinna AD. Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate. J Hepatol 2013; 58 (03) 609-618
  • 85 Cucchetti A, Ercolani G, Vivarelli M. et al. Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis. Liver Transpl 2006; 12 (06) 966-971
  • 86 Lee MW, Raman SS, Asvadi NH. et al. Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: a 10-year intention-to-treat analysis. Hepatology 2017; 65 (06) 1979-1990
  • 87 Raj R, Wehrle CJ, Aykun N. et al. Immunotherapy plus locoregional therapy leading to curative-intent hepatectomy in HCC: proof of concept producing durable survival benefits detectable with liquid biopsy. Cancers (Basel) 2023; 15 (21) 5220
  • 88 Cheng AL, Qin S, Ikeda M. et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol 2022; 76 (04) 862-873
  • 89 Chow P. et al. Abstract CT003: IMbrave050: Phase 3 study of adjuvant atezolizumab +bevacizumab versus active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. Cancer Res 2023; 83 (8, Suppl): CT003-CT003
  • 90 Finn RS, Qin S, Ikeda M. et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020; 382 (20) 1894-1905
  • 91 Aliseda D, Martí-Cruchaga P, Zozaya G. et al. Liver resection and transplantation following yttrium-90 radioembolization for primary malignant liver tumors: a 15-year single-center experience. Cancers (Basel) 2023; 15 (03) 733
  • 92 Shaker TM, Eason JD, Davidson BR. et al; ERS4OLT.org Working Group. Which cava anastomotic techniques are optimal regarding immediate and short-term outcomes after liver transplantation: a systematic review of the literature and expert panel recommendations. Clin Transplant 2022; 36 (10) e14681