Radioembolization for Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fastest-growing cancer worldwide, causing significant morbidity and mortality. Surgical resection, ablation, or transplantation is the best treatment option for patients with HCC. However, only about one-fifth of patients are suitable for such primary curative treatments due to underlying liver disease or rapid extension of the tumor. Image-guided locoregional therapies may prove an important alternative in this scenario, particularly transarterial radioembolization (TARE) with yttrium-90 (Y-90). Based on many studies, TARE can be considered a curative treatment option for patients with early-stage HCC, a bridge to transplantation, and a method for downstaging tumors to give patients with unresectable HCC a chance to potentially receive a curative treatment. TARE can be also combined with other treatment modalities to provide a better quality of life in patients when compared with systemic therapy in patients with unresectable HCC. Here, we discuss the use of TARE in the approach to HCC patients who are in early, intermediate, or advanced stages.

Keywords

hepatocellular carcinoma - radioembolization - yttrium-90 - ablation - resection - transplantation

Publikationsverlauf

Eingereicht: 08. Februar 2021

Angenommen: 24. Mai 2021

Artikel online veröffentlicht:
08. Juli 2021

• References

• 1 Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019; 16 (10) 589-604
• 2 Gelband H, Chen CJ, Chen W. et al. Liver cancer. In: Gelband H, Jha P, Sankaranarayanan R, Horton S. ed. Cancer: Disease Control Priorities. 3rd ed, Vol 3. Washington, DC: 2015
• 3 Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018; 391 (10127): 1301-1314
• 4 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (01) 7-34
• 5 Saini A, Wallace A, Alzubaidi S. et al. History and evolution of yttrium-90 radioembolization for hepatocellular carcinoma. J Clin Med 2019; 8 (01) E55
• 6 Younossi Z, Stepanova M, Ong JP. et al; Global Nonalcoholic Steatohepatitis Council. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol 2019; 17 (04) 748-755.e3 , e743
• 7 Balogh J, Victor III D, Asham EH. et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016; 3: 41-53
• 8 Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53 (03) 1020-1022
• 9 Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg 2015; 261 (05) 947-955
• 10 Al-Kalbani A, Kamel Y. Y-90 microshperes in the treatment of unresectable hepatocellular carcinoma. Saudi J Gastroenterol 2008; 14 (02) 90-92
• 11 Ho S, Lau WY, Leung TW. et al. Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with ⁹⁹Tcm macroaggregated albumin. Br J Radiol 1997; 70 (836) 823-828
• 12 Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives. Hepatology 2013; 58 (06) 2188-2197
• 13 Ariel IM. Treatment of inoperable primary pancreatic and liver cancer by the intra-arterial administration of radioactive isotopes (Y90 radiating microspheres). Ann Surg 1965; 162: 267-278
• 14 Kallini JR, Gabr A, Salem R, Lewandowski RJ. Transarterial radioembolization with yttrium-90 for the treatment of hepatocellular carcinoma. Adv Ther 2016; 33 (05) 699-714
• 15 Sharma RA, Van Hazel GA, Morgan B. et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 2007; 25 (09) 1099-1106
• 16 Salem R, Gabr A, Riaz A. et al. Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience. Hepatology 2018; 68 (04) 1429-1440
• 17 Lewandowski RJ, Gabr A, Abouchaleh N. et al. Radiation segmentectomy: potential curative therapy for early hepatocellular carcinoma. Radiology 2018; 287 (03) 1050-1058
• 18 Riaz A, Gates VL, Atassi B. et al. Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys 2011; 79 (01) 163-171
• 19 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
• 20 Kulik L. Criteria for liver transplantation in hepatocellular carcinoma. Clin Liver Dis (Hoboken) 2015; 6 (04) 100-102
• 21 Mehta N, Sarkar M, Dodge JL, Fidelman N, Roberts JP, Yao FY. Intention to treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl 2016; 22 (02) 178-187
• 22 Lewandowski RJ, Kulik LM, Riaz A. et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant 2009; 9 (08) 1920-1928
• 23 Kulik L, Heimbach JK, Zaiem F. et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology 2018; 67 (01) 381-400
• 24 Salem R, Lewandowski RJ, Kulik L. et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011; 140 (02) 497-507.e2 , e492
• 25 Kao WY, Chao Y, Chang CC. et al. Prognosis of early-stage hepatocellular carcinoma: the clinical implications of substages of Barcelona Clinic Liver Cancer System based on a cohort of 1265 patients. Medicine (Baltimore) 2015; 94 (43) e1929
• 26 Cho IR, Lee HW, Song KJ. et al. Conditional survival estimate in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy with/without concurrent radiotherapy. Oncotarget 2017; 8 (45) 79914-79926
• 27 European Association for the Study of the Liver. Electronic address: [e-mail]; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018; 69 (01) 182-236
• 28 Kikuchi L, Menezes M, Chagas AL. et al. Percutaneous radiofrequency ablation for early hepatocellular carcinoma: risk factors for survival. World J Gastroenterol 2014; 20 (06) 1585-1593
• 29 Shiina S, Sato K, Tateishi R. et al. Percutaneous ablation for hepatocellular carcinoma: comparison of various ablation techniques and surgery. Can J Gastroenterol Hepatol 2018; 2018: 4756147
• 30 Choi D, Lim HK, Rhim H. et al. Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series. Eur Radiol 2007; 17 (03) 684-692
• 31 Lahat E, Eshkenazy R, Zendel A. et al. Complications after percutaneous ablation of liver tumors: a systematic review. Hepatobiliary Surg Nutr 2014; 3 (05) 317-323
• 32 Gilbert P, Arrington D, Yamada R. et al. Protective techniques in image-guided percutaneous hepatic ablations. Intervent Oncol 360 2016; 4 (05) E75-E85
• 33 Song I, Rhim H, Lim HK, Kim YS, Choi D. Percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the diaphragm and gastrointestinal tracts with the use of artificial ascites: safety and technical efficacy in 143 patients. Eur Radiol 2009; 19 (11) 2630-2640
• 34 Kondo Y, Yoshida H, Shiina S, Tateishi R, Teratani T, Omata M. Artificial ascites technique for percutaneous radiofrequency ablation of liver cancer adjacent to the gastrointestinal tract. Br J Surg 2006; 93 (10) 1277-1282
• 35 Salem R, Thurston KG. Radioembolization with ⁹⁰yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations. J Vasc Interv Radiol 2006; 17 (08) 1251-1278
• 36 Vouche M, Lewandowski RJ, Atassi R. et al. Radiation lobectomy: time-dependent analysis of future liver remnant volume in unresectable liver cancer as a bridge to resection. J Hepatol 2013; 59 (05) 1029-1036
• 37 Lau WY, Leung WT, Ho S. et al. Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer 1994; 70 (05) 994-999
• 38 Dawson LA, Ten Haken RK. Partial volume tolerance of the liver to radiation. Semin Radiat Oncol 2005; 15 (04) 279-283
• 39 Edeline J, Touchefeu Y, Guiu B. et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol 2020; 6 (01) 51-59
• 40 Benson III AB, Geschwind JF, Mulcahy MF. et al. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013; 49 (15) 3122-3130
• 41 Atassi B, Bangash AK, Lewandowski RJ. et al. Biliary sequelae following radioembolization with yttrium-90 microspheres. J Vasc Interv Radiol 2008; 19 (05) 691-697
• 42 Riaz A, Lewandowski RJ, Kulik LM. et al. Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J Vasc Interv Radiol 2009; 20 (09) 1121-1130 , quiz 1131
• 43 Kim HC, Joo I, Lee M, Chung JW. Benign biliary stricture after yttrium-90 radioembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2020; 31 (12) 2014-2021
• 44 Gabr A, Ranganathan S, Mouli SK. et al. Streamlining radioembolization in UNOS T1/T2 hepatocellular carcinoma by eliminating lung shunt estimation. J Hepatol 2020; 72 (06) 1151-1158
• 45 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
• 46 Leung JY, Zhu AX, Gordon FD. et al. Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. Liver Transpl 2004; 10 (11) 1343-1354
• 47 Schoenberg MB, Bucher JN, Vater A. et al. Resection or transplant in early hepatocellular carcinoma. Dtsch Arztebl Int 2017; 114 (31-32): 519-526
• 48 Lencioni R, Cioni D, Crocetti L. et al. Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 2005; 234 (03) 961-967
• 49 von Felden J, Schulze K, Krech T. et al. Circulating tumor cells as liquid biomarker for high HCC recurrence risk after curative liver resection. Oncotarget 2017; 8 (52) 89978-89987
• 50 Biederman D, Titano J, Bishay V, Durrani R, Dayan E. Radiation segmentectomy vs. microwave ablation for unresectable solitary hepatocellular carcinoma ≤3 cm: a propensity score matching study. J Vasc Interv Radiol 2016; 27 (03) S5-S6
• 51 Arndt L, Villalobos A, Wagstaff W. et al. Evaluation of medium-term efficacy of Y90 radiation segmentectomy vs percutaneous microwave ablation in patients with solitary surgically unresectable < 4 cm hepatocellular carcinoma: a propensity score matched study. Cardiovasc Intervent Radiol 2021; 44 (03) 401-413
• 52 Gordon AC, Gabr A, Riaz A. et al. Radioembolization super survivors: extended survival in non-operative hepatocellular carcinoma. Cardiovasc Intervent Radiol 2018; 41 (10) 1557-1565
• 53 Humar A, Beissel J, Crotteau S, Kandaswamy R, Lake J, Payne W. Whole liver versus split liver versus living donor in the adult recipient: an analysis of outcomes by graft type. Transplantation 2008; 85 (10) 1420-1424
• 54 Titano J, Voutsinas N, Kim E. The role of radioembolization in bridging and downstaging hepatocellular carcinoma to curative therapy. Semin Nucl Med 2019; 49 (03) 189-196
• 55 Abdelfattah MR, Al-Sebayel M, Broering D, Alsuhaibani H. Radioembolization using yttrium-90 microspheres as bridging and downstaging treatment for unresectable hepatocellular carcinoma before liver transplantation: initial single-center experience. Transplant Proc 2015; 47 (02) 408-411
• 56 Zori AG, Ismael MN, Limaye AR. et al. Locoregional therapy protocols with and without radioembolization for hepatocellular carcinoma as bridge to liver transplantation. Am J Clin Oncol 2020; 43 (05) 325-333
• 57 Sheth RA, Patel MS, Koottappillil B. et al. Role of locoregional therapy and predictors for dropout in patients with hepatocellular carcinoma listed for liver transplantation. J Vasc Interv Radiol 2015; 26 (12) 1761-1768 , quiz 1768
• 58 Kim DY, Han KH. Transarterial chemoembolization versus transarterial radioembolization in hepatocellular carcinoma: optimization of selecting treatment modality. Hepatol Int 2016; 10 (06) 883-892
• 59 Zhang Y, Li Y, Ji H, Zhao X, Lu H. Transarterial Y90 radioembolization versus chemoembolization for patients with hepatocellular carcinoma: a meta-analysis. Biosci Trends 2015; 9 (05) 289-298
• 60 Garwood ER, Fidelman N, Hoch SE, Kerlan Jr RK, Yao FY. Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction. Liver Transpl 2013; 19 (02) 164-173
• 61 Gabr A, Kallini JR, Gates VL. et al. Same-day ⁹⁰Y radioembolization: implementing a new treatment paradigm. Eur J Nucl Med Mol Imaging 2016; 43 (13) 2353-2359
• 62 Salem R, Gilbertsen M, Butt Z. et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 2013; 11 (10) 1358-1365.e1 , e1351
• 63 Kirchner T, Marquardt S, Werncke T. et al. Comparison of health-related quality of life after transarterial chemoembolization and transarterial radioembolization in patients with unresectable hepatocellular carcinoma. Abdom Radiol (NY) 2019; 44 (04) 1554-1561
• 64 Salem R, Gordon AC, Mouli S. et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2016; 151 (06) 1155-1163.e2 , e1152
• 65 Golfieri R, Cappelli A, Cucchetti A. et al. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas. Hepatology 2011; 53 (05) 1580-1589
• 66 Rubinstein MM, Kaubisch A, Kinkhabwala M, Reinus J, Liu Q, Chuy JW. Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation. J Gastrointest Oncol 2017; 8 (06) 1051-1055
• 67 Mohamed M, Katz AW, Tejani MA. et al. Comparison of outcomes between SBRT, yttrium-90 radioembolization, transarterial chemoembolization, and radiofrequency ablation as bridge to transplant for hepatocellular carcinoma. Adv Radiat Oncol 2015; 1 (01) 35-42
• 68 Gordon-Weeks AN, Snaith A, Petrinic T, Friend PJ, Burls A, Silva MA. Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg 2011; 98 (09) 1201-1208
• 69 Heimbach JK, Kulik LM, Finn RS. et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67 (01) 358-380
• 70 Parikh ND, Waljee AK, Singal AG. Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transpl 2015; 21 (09) 1142-1152
• 71 Schaub SK, Hartvigson PE, Lock MI. et al. Stereotactic body radiation therapy for hepatocellular carcinoma: current trends and controversies. Technol Cancer Res Treat 2018; 17: 1533033818790217
• 72 Erratum: Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transpl 2016; 22 (01) 138
• 73 Han K, Kim JH. Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system. World J Gastroenterol 2015; 21 (36) 10327-10335
• 74 Arellano RS. What's new in percutaneous ablative strategies for hepatocellular carcinoma and colorectal hepatic metastases? 2020 update. Curr Oncol Rep 2020; 22 (10) 105
• 75 Tang C, Shen J, Feng W. et al. combination therapy of radiofrequency ablation and transarterial chemoembolization for unresectable hepatocellular carcinoma: a retrospective study. Medicine (Baltimore) 2016; 95 (20) e3754
• 76 Yuan W, Yang MJ, Xu J. et al. Radiofrequency ablation combined with transarterial chemoembolization for specially located small hepatocellular carcinoma. Technol Cancer Res Treat 2018; 17: 1533033818788529
• 77 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
• 78 Vogel A, Cervantes A, Chau I. et al; ESMO Guidelines Committee. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29 (Suppl. 04) iv238-iv255
• 79 Benson III AB, D'Angelica MI, Abbott DE. et al. NCCN guidelines insights: hepatobiliary cancers, version 1.2017. J Natl Compr Canc Netw 2017; 15 (05) 563-573
• 80 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
• 81 Sangro B, Carpanese L, Cianni R. et al; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011; 54 (03) 868-878
• 82 Mazzaferro V, Sposito C, Bhoori S. et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013; 57 (05) 1826-1837
• 83 Liu PH, Huo TI, Miksad RA. Hepatocellular carcinoma with portal vein tumor involvement: best management strategies. Semin Liver Dis 2018; 38 (03) 242-251
• 84 Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: beyond the known frontiers. World J Gastroenterol 2019; 25 (31) 4360-4382
• 85 Qadan M, Kothary N, Sangro B, Palta M. The treatment of hepatocellular carcinoma with portal vein tumor thrombosis. Am Soc Clin Oncol Educ Book 2020; 40: 1-8
• 86 Quirk M, Kim YH, Saab S, Lee EW. Management of hepatocellular carcinoma with portal vein thrombosis. World J Gastroenterol 2015; 21 (12) 3462-3471
• 87 Salem R, Lewandowski R, Roberts C. et al. Use of yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis. J Vasc Interv Radiol 2004; 15 (04) 335-345
• 88 Kokabi N, Camacho JC, Xing M. et al. Open-label prospective study of the safety and efficacy of glass-based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis. Cancer 2015; 121 (13) 2164-2174
• 89 Facciorusso A, Bargellini I, Cela M, Cincione I, Sacco R. Comparison between Y90 radioembolization plus sorafenib and Y90 radioembolization alone in the treatment of hepatocellular carcinoma: a propensity score analysis. Cancers (Basel) 2020; 12 (04) E897
• 90 Chow PKH, Gandhi M, Tan SB. et al; Asia-Pacific Hepatocellular Carcinoma Trials Group. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018; 36 (19) 1913-1921
• 91 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
• 92 Vilgrain V, Pereira H, Assenat E. et al; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol 2017; 18 (12) 1624-1636
• 93 Finn RS, Ryoo BY, Merle P. et al; KEYNOTE-240 Investigators. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol 2020; 38 (03) 193-202
• 94 El-Khoueiry AB, Sangro B, Yau T. et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017; 389 (10088): 2492-2502
• 95 Yau T, Kang Y-K, Kim T-Y. et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040. J Clin Oncol 2019; 37 (15, Suppl): 4012-4012
• 96 Kelley RK, Abou-Alfa GK, Bendell JC. et al. Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses. J Clin Oncol 2017; 35 (15, Suppl): 4073-4073
• 97 Zhan C, Ruohoniemi D, Shanbhogue KP. et al. Safety of combined yttrium-90 radioembolization and immune checkpoint inhibitor immunotherapy for hepatocellular carcinoma. J Vasc Interv Radiol 2020; 31 (01) 25-34
• 98 Nabrinsky E, James E. Highlighting survival with yttrium-90 radioembolization therapy in unresectable hepatocellular carcinoma. Cureus 2020; 12 (05) e8163
• 99 Safety and Efficacy Study of Radioembolization in Combination With Durvalumab in Locally Advanced and Unresectable HCC (SOLID). Available at: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04124991&cntry=&state=&city=&dist=
• 100 Duffy AG, Ulahannan SV, Makorova-Rusher O. et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017; 66 (03) 545-551
• 101 Xie C, Duffy AG, Mabry-Hrones D. et al. Tremelimumab in combination with microwave ablation in patients with refractory biliary tract cancer. Hepatology 2019; 69 (05) 2048-2060
• 102 Nivolumab and Y-90 in treating patients with liver cancer undergoing surgery. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03812562?term=NCT03812562&draw=2&rank=1
• 103 Bouvry C, Palard X, Edeline J. et al. Transarterial radioembolization (TARE) agents beyond ⁹⁰Y-microspheres. BioMed Res Int 2018; 2018: 1435302
• 104 Wai Ling Khoo TS, Rehman A, Olynyk JK. Tyrosine kinase inhibitors in the treatment of hepatocellular carcinoma. In: Tirnitz-Parker JEE. ed. Hepatocellular Carcinoma. Brisbane, Australia: 2019