Harnessing yttrium-90 selective internal radiation therapy for primary hepatocellular carcinoma: Mechanisms of action and combination strategies

Abstract

Yttrium-90 selective internal radiation therapy (90Y-SIRT) has emerged as a transformative locoregional modality for primary hepatocellular carcinoma (HCC) with distinct radiobiological advantages and favorable safety profiles. 90Y-SIRT is expected to break through the limitations of conventional treatment by combining it with other systemic therapies in the treatment of liver cancer at all stages. This review systematically examines: (i) The four mechanistic foundations of SIRT’s therapeutic efficacy, including precise arterial delivery of microspheres, sustained low-dose-rate β-irradiation, tumor-selective high-dose escalation, and modulation of the tumor immune microenvironment; (ii) clinical evidence supporting its dual role in downstaging advanced HCC with portal vein tumor thrombus and enhancing systemic therapy efficacy in intermediate-stage disease; and (iii) comparative studies demonstrating its superiority over transarterial chemoembolization in terms of tumor response, resectability or transplant conversion, and treatment tolerability. In addition, we discuss emerging directions, including the development of cost-effective domestically manufactured microspheres and the integration of biomarker-guided combination regimens to potentiate immunogenic synergy. By integrating mechanistic insights with clinical validation, this review positions 90Y-SIRT as a central pillar in the evolving landscape of precision medicine for primary HCC.

Keywords

Yttrium-90 selective internal radiation therapy / Primary hepatocellular carcinoma / Microsphere embolization / Low-dose-rate irradiation

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. doi: 10.1038/s41571-023-00825-3

[2] Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018; 391(10127):1301-1314. doi: 10.1016/s0140-6736(18)30010-2

[3] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3):209-249. doi: 10.3322/caac.21660

[4] Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020; 382(20):1894-1905. doi: 10.1056/NEJMoa1915745

[5] Yau T, Park JW, Finn RS, et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): A randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2022; 23(1):77-90. doi: 10.1016/s1470-2045(21)00604-5

[6] Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The checkMate 040 randomized clinical trial. JAMA Oncol. 2020; 6(11):e204564. doi: 10.1001/jamaoncol.2020.4564

[7] Qu K, Yan Z, Wu Y, et al. Transarterial chemoembolization aggravated peritumoral fibrosis via hypoxia-inducible factor-1α dependent pathway in hepatocellular carcinoma. J Gastroenterol Hepatol. 2015; 30(5):925-32. doi: 10.1111/jgh.12873

[8] Liu L, Teng G, Zhang D, et al. Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs. Chin Med J (Engl). 1999; 112(7):632-636.

[9] Hamad A, Aziz H, Kamel IR, Diaz DA, Pawlik TM. Yttrium-90 Radioembolization: Current indications and outcomes. J Gastrointest Surg. 2023; 27(3):604-614. doi: 10.1007/s11605-022-05559-8

[10] D’Abadie P, Walrand S, Lhommel R, Hesse M, Borbath I, Jamar F. Optimization of the clinical effectiveness of radioembolization in hepatocellular carcinoma with dosimetry and patient-selection criteria. Curr Oncol. 2022; 29(4):2422-2434. doi: 10.3390/curroncol29040196

[11] Mansur A, Habibollahi P, Fang A, et al. New frontiers in radioembolization. Ther Adv Med Oncol. 2024; 16:17588359241280692. doi: 10.1177/17588359241280692

[12] Cremonesi M, Chiesa C, Strigari L, et al. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol. 2014; 4:210. doi: 10.3389/fonc.2014.00210

[13] Ibrahim SM, Lewandowski RJ, Sato KT, et al. Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review. World J Gastroenterol. 2008; 14(11):1664-1669. doi: 10.3748/wjg.14.1664

[14] Mosconi C, Cappelli A, Pettinato C, Golfieri R. Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives. World J Hepatol. 2015; 7(5):738-752. doi: 10.4254/wjh.v7.i5.738

[15] Chen ZH, Zhang XP, Lu YG, et al. Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: A nationwide study. Hepatol Int. 2020; 14(5): 754-764. doi: 10.1007/s12072-020-10032-2

[16] Choi C, Yoo GS, Cho WK, Park HC. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma. World J Gastroenterol. 2019; 25(20):2416-2429. doi: 10.3748/wjg.v25.i20.2416

[17] Choi JW, Kim HC. Radioembolization for hepatocellular carcinoma: What clinicians need to know. J Liver Cancer. 2022; 22(1):4-13. doi: 10.17998/jlc.2022.01.16

[18] Fidelman N, Kerlan RK, Jr. Transarterial chemoembolization and (90)Y radioembolization for hepatocellular carcinoma: Review of current applications beyond intermediate-stage disease. AJR Am J Roentgenol. 2015; 205(4):742-752. doi: 10.2214/ajr.15.14802

[19] De La Torre-Aláez M, Matilla A, Varela M, et al. Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: A phase 2, single-arm study. J Immunother Cancer. 2022; 10(11):e005457. doi: 10.1136/jitc-2022-005457

[20] Liu DM, Leung TW, Chow PK, et al. Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia. Int J Surg. 2022; 102:106094. doi: 10.1016/j.ijsu.2021.106094

[21] Lewandowski RJ, Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Semin Intervent Radiol. 2006; 23(1):64-72. doi: 10.1055/s-2006-939842

[22] Kim SP, Cohalan C, Kopek N, Enger SA. A guide to 90Y radioembolization and its dosimetry. Phys Med. 2019; 68: 132-145. doi: 10.1016/j.ejmp.2019.09.236

[23] Singh P, Anil G. Yttrium-90 radioembolization of liver tumors: What do the images tell us? Cancer Imaging. 2014; 13(4):645-657. doi: 10.1102/1470-7330.2013.0057

[24] Molvar C, Lewandowski R. Yttrium-90 radioembolization of hepatocellular carcinoma-performance, technical advances, and future concepts. Semin Intervent Radiol. 2015; 32(4):388-397. doi: 10.1055/s-0035-1564704

[25] Anbari Y, Veerman FE, Keane G, et al. Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer. J Interv Med. 2023; 6(4):153-159. doi: 10.1016/j.jimed.2023.09.001

[26] Choi SH, Seong J. Strategic application of radiotherapy for hepatocellular carcinoma. Clin Mol Hepatol. 2018; 24(2): 114-134. doi: 10.3350/cmh.2017.0073

[27] Fuss M, Salter BJ, Herman TS, Thomas CR Jr. External beam radiation therapy for hepatocellular carcinoma: Potential of intensity-modulated and image-guided radiation therapy. Gastroenterology. 2004; 127(5Suppl 1): S206-S217. doi: 10.1053/j.gastro.2004.09.035

[28] Dudzinski SO, Newman NB, McIntyre J, et al. Emerging evidence-based role for external-beam radiation therapy in hepatocellular carcinoma. Lancet Gastroenterol Hepatol. 2025; 10(4):387-398. doi: 10.1016/s2468-1253(24)00267-x

[29] Song CW, Glatstein E, Marks LB, et al. Biological principles of stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS): Indirect cell death. Int J Radiat Oncol Biol Phys. 2021; 110(1):21-34. doi: 10.1016/j.ijrobp.2019.02.047

[30] 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(6):2188-2197. doi: 10.1002/hep.26382

[31] De La Garza-Ramos C, Toskich BB. Radioembolization for the treatment of hepatocellular carcinoma: The road to personalized dosimetry and ablative practice. Semin Intervent Radiol. 2021; 38(4):466-471. doi: 10.1055/s-0041-1735571

[32] Wright CL, Zhang J, Tweedle MF, Knopp MV, Hall NC. Theranostic imaging of yttrium-90. Biomed Res Int. 2015; 2015:481279. doi: 10.1155/2015/481279

[33] Piron B, Paillas S, Boudousq V, et al. DNA damage-centered signaling pathways are effectively activated during low dose-rate Auger radioimmunotherapy. Nucl Med Biol. 2014; 41 Suppl: e75-e83. doi: 10.1016/j.nucmedbio.2014.01.012

[34] Melia E, Parsons JL. DNA damage and repair dependencies of ionising radiation modalities. Biosci Rep. 2023; 43(10):BSR20222586. doi: 10.1042/bsr20222586

[35] Thoms J, Bristow RG. DNA repair targeting and radiotherapy: A focus on the therapeutic ratio. Semin Radiat Oncol. 2010; 20(4):217-222. doi: 10.1016/j.semradonc.2010.06.003

[36] Tauchi H, Nakamura N, Komatsu K, Sawada S. Accumulation of cells at G2/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by 252Cf fission neutrons. J Radiat Res. 1996; 37(1):49-57. doi: 10.1269/jrr.37.49

[37] Hami R, Apeke S, Redou P, et al. Predicting the tumour response to radiation by modelling the five Rs of radiotherapy using PET images. J Imaging. 2023; 9(6):124. doi: 10.3390/jimaging9060124

[38] Garin E, Tselikas L, Guiu B, et al. 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(1):17-29. doi: 10.1016/s2468-1253(20)30290-9

[39] Lee BQ, Abbott EM, Able S, et al. Radiosensitivity of colorectal cancer to 90Y and the radiobiological implications for radioembolisation therapy. Phys Med Biol. 2019; 64(13):135018. doi: 10.1088/1361-6560/ab23c4

[40] Tanguturi SK, Wo JY, Zhu AX, Dawson LA, Hong TS. Radiation therapy for liver tumors: Ready for inclusion in guidelines? Oncologist. 2014; 19(8):868-879. doi: 10.1634/theoncologist.2014-0097

[41] Boughdad S, Duran R, Prior JO, et al. Measure of 90Y-glass microspheres residue post-TARE using PET/CT and potential impact on tumor absorbed dose in comparison 99]mTc-MAA SPECT/CT dosimetry. EJNMMI Rep. 2024; 8(1):26. doi: 10.1186/s41824-024-00214-8

[42] Torkian P, Haghshomar M, Farsad K, Wallace S, Golzarian J, Young SJ. Cancer immunology: Impact of radioembolization of hepatocellular carcinoma on immune response modulation. AJR Am J Roentgenol. 2023; 220(6):863-872. doi: 10.2214/ajr.22.28800

[43] Wang X, Zhang H, Zhang X, Liu Y. Abscopal effect: From a rare phenomenon to a new frontier in cancer therapy. Biomark Res. 2024; 12(1):98. doi: 10.1186/s40364-024-00628-3

[44] Liu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors. J Hematol Oncol. 2018; 11(1):104. doi: 10.1186/s13045-018-0647-8

[45] D’Alonzo RA, Keam S, Gill S, et al. Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model. Cancer Immunol Immunother. 2025; 74(2):44. doi: 10.1007/s00262-024-03889-x

[46] Virani NA, Kelada OJ, Kunjachan S, et al. Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption. PLoS One. 2020; 15(7):e0236245. doi: 10.1371/journal.pone.0236245

[47] Vallée A, Lecarpentier Y, Guillevin R, Vallée JN. Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis. Oncotarget. 2017; 8(52):90579-90604. doi: 10.18632/oncotarget.21234

[48] Chen J, Wang S, Ding Y, Xu D, Zheng S. Radiotherapy-induced alterations in tumor microenvironment: Metabolism and immunity. Front Cell Dev Biol. 2025; 13:1568634. doi: 10.3389/fcell.2025.1568634

[49] Liu S, Wang W, Hu S, et al. Radiotherapy remodels the tumor microenvironment for enhancing immunotherapeutic sensitivity. Cell Death Dis. 2023; 14(10):679. doi: 10.1038/s41419-023-06211-2

[50] Belisario DC, Kopecka J, Pasino M, et al. Hypoxia dictates metabolic rewiring of tumors: Implications for chemoresistance. Cells. 2020; 9(12):2598. doi: 10.3390/cells9122598

[51] Li M, Liu D, Lee D, et al. Targeted alpha-particle radiotherapy and immune checkpoint inhibitors induces cooperative inhibition on tumor growth of malignant melanoma. Cancers (Basel). 2021; 13(15):3676. doi: 10.3390/cancers13153676

[52] Tai D, Loke K, Gogna A, et al. Radioembolisation with Y90-resin microspheres followed by nivolumab for advanced hepatocellular carcinoma (CA 209-678): A single arm, single centre, phase 2 trial. Lancet Gastroenterol Hepatol. 2021; 6(12):1025-1035. doi: 10.1016/s2468-1253(21)00305-8

[53] Kadalayil L, Benini R, Pallan L, et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer. Ann Oncol. 2013; 24(10):2565-2570. doi: 10.1093/annonc/mdt247

[54] 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(2):497-507.e2. doi: 10.1053/j.gastro.2010.10.049

[55] Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022; 76(3):681-693. doi: 10.1016/j.jhep.2021.11.018

[56] Brown AM, Kassab I, Massani M, et al. TACE versus TARE for patients with hepatocellular carcinoma: Overall and individual patient level meta analysis. Cancer Med. 2023; 12(3):2590-2599. doi: 10.1002/cam4.5125

[57] Dhondt E, Lambert B, Hermie L, et al. 90Y radioembolization versus drug-eluting bead chemoembolization for unresectable hepatocellular carcinoma: Results from the TRACE phase II randomized controlled trial. Radiology. 2022; 303(3):699-710. doi: 10.1148/radiol.211806

[58] Patel KR, Menon H, Patel RR, Huang EP, Verma V, Escorcia FE. Locoregional therapies for hepatocellular carcinoma: A systematic review and meta-analysis. JAMA Netw Open. 2024; 7(11):e2447995. doi: 10.1001/jamanetworkopen.2024.47995

[59] Hao K, Paik AJ, Han LH, Makary MS. Yttrium-90 radioembolization treatment strategies for management of hepatocellular carcinoma. World J Radiol. 2024; 16(10): 512-527. doi: 10.4329/wjr.v16.i10.512

[60] Lu H, Liang B, Xia X, Zheng C. Predictors and risk factors of bile duct injury after transcatheter arterial chemoembolization for hepatocellular carcinoma. BMC Cancer. 2024; 24(1):1085. doi: 10.1186/s12885-024-12864-9

[61] Yuan Y, He W, Yang Z, et al. TACE-HAIC combined with targeted therapy and immunotherapy versus TACE alone for hepatocellular carcinoma with portal vein tumour thrombus: A propensity score matching study. Int J Surg. 2023; 109(5):1222-1230. doi: 10.1097/js9.0000000000000256

[62] Lee SM, Choi JH, Yoon JH, et al. Efficacy and safety of image-guided hypofractionated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: A retrospective, multicenter study. BMC Cancer. 2025; 25(1):736. doi: 10.1186/s12885-025-13739-3

[63] Jiang JF, Lao YC, Yuan BH, et al. Treatment of hepatocellular carcinoma with portal vein tumor thrombus: Advances and challenges. Oncotarget. 2017; 8(20):33911-33921. doi: 10.18632/oncotarget.15411

[64] Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol. 2006; 12(47):7561-7567. doi: 10.3748/wjg.v12.i47.7561

[65] Ormiston W, Samuelson S, Van Wyk M, et al. Safety and efficacy of selective internal radiation therapy for portal vein tumour thrombus in advanced hepatocellular carcinoma: A single-centre experience in Australia. J Med Imaging Radiat Oncol. 2025; 69(2):244-250. doi: 10.1111/1754-9485.13837

[66] Jia Z, Jiang G, Tian F, Zhu C, Qin X. A systematic review on the safety and effectiveness of yttrium-90 radioembolization for hepatocellular carcinoma with portal vein tumor thrombosis. Saudi J Gastroenterol. 2016; 22(5):353-359. doi: 10.4103/1319-3767.191139

[67] Hur MH, Cho Y, Kim DY, et al. Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis. Clin Mol Hepatol. 2023; 29(3):763-778. doi: 10.3350/cmh.2023.0076

[68] Ma YN, Jiang X, Liu H, Song P, Tang W. Conversion therapy for initially unresectable hepatocellular carcinoma: Current status and prospects. Biosci Trends. 2024; 17(6):415-426. doi: 10.5582/bst.2023.01322

[69] 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(6):1155-1163.e2. doi: 10.1053/j.gastro.2016.08.029

[70] 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(8):1920-1928. doi: 10.1111/j.1600-6143.2009.02695.x

[71] 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(9):843-850. doi: 10.1016/s2468-1253(22)00091-7

[72] Salem R, Johnson GE, Kim E, et al. Yttrium-90 radioembolization for the treatment of solitary, unresectable HCC: The LEGACY study. Hepatology. 2021; 74(5):2342-2352. doi: 10.1002/hep.31819

[73] Salem R, Padia SA, Lam M, et al. Clinical and dosimetric considerations for Y90: Recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging. 2019; 46(8):1695-1704. doi: 10.1007/s00259-019-04340-5

[74] Entezari P, Gabr A, Kennedy K, Salem R, Lewandowski RJ. Radiation lobectomy: An overview of concept and applications, technical considerations, outcomes. Semin Intervent Radiol. 2021; 38(4):419-424. doi: 10.1055/s-0041-1735530

[75] Birgin E, Rasbach E, Seyfried S, et al. Contralateral liver hypertrophy and oncological outcome following radioembolization with 90Y-microspheres: A systematic review. Cancers (Basel). 2020; 12(2):294. doi: 10.3390/cancers12020294

[76] Villalobos A, Pisanie JLD, Gandhi RT, Kokabi N. Yttrium-90 radioembolization dosimetry: Dose considerations, optimization, and tips. Semin Intervent Radiol. 2024; 41(1): 63-78. doi: 10.1055/s-0044-1779715

[77] Baker T, Tabrizian P, Zendejas I, et al. Conversion to resection post radioembolization in patients with HCC: Recommendations from a multidisciplinary working group. HPB (Oxford). 2022; 24(7):1007-1018. doi: 10.1016/j.hpb.2021.12.013

[78] Jia Z, Wang C, Paz-Fumagalli R, Wang W. dosimetry, Radiation segmentectomy for hepatic malignancies: Indications, devices, procedure, clinical outcomes, and toxicity of yttrium-90 microspheres. J Interv Med. 2019; 2(1):1-4. doi: 10.1016/j.jimed.2019.05.001

[79] Mourad SN, De La Garza-Ramos C, Toskich BB. Radiation segmentectomy for the treatment of hepatocellular carcinoma: A practical review of evidence. Cancers (Basel). 2024; 16(3):669. doi: 10.3390/cancers16030669

[80] Prachanronarong K, Kim E. Radiation segmentectomy. Semin Intervent Radiol. 2021; 38(4):425-431. doi: 10.1055/s-0041-1735529

[81] 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(6):1164-1174. doi: 10.1016/j.jhep.2019.08.006

[82] Craciun L, De Wind R, Demetter P, et al. Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: A rationale for combining selective internal radiation therapy (SIRT) and immunotherapy. BMC Cancer. 2020; 20(1):135. doi: 10.1186/s12885-020-6613-1

[83] Lee YB, Nam JY, Cho EJ, et al. A phase I/IIa trial of yttrium-90 radioembolization in combination with durvalumab for locally advanced unresectable hepatocellular carcinoma. Clin Cancer Res. 2023; 29(18):3650-3658. doi: 10.1158/1078-0432.Ccr-23-0581

[84] Yu S, Yu M, Keane B, et al. A pilot study of pembrolizumab in combination with Y90 radioembolization in subjects with poor prognosis hepatocellular carcinoma. Oncologist. 2024; 29(3):270-e413. doi: 10.1093/oncolo/oyad331

[85] 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(1):25-34. doi: 10.1016/j.jvir.2019.05.023

[86] Chow PK, Poon DY, Khin MW, et al. Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma. PLoS One. 2014; 9(3):e90909. doi: 10.1371/journal.pone.0090909

[87] Salman A, Simoneau E, Hassanain M, et al. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma. Curr Oncol. 2016; 23(5):e472-e480. doi: 10.3747/co.23.2827

[88] Villalobos A, Dabbous HH, Little O, et al. Safety and efficacy of concurrent atezolizumab/bevacizumab or nivolumab combination therapy with yttrium-90 radioembolization of advanced unresectable hepatocellular carcinoma. Curr Oncol. 2023; 30(12):10100-10110. doi: 10.3390/curroncol30120734

[89] Mejait A, Roux C, Soret M, et al. Enhanced therapeutic outcomes with atezolizumab-bevacizumab and SIRT combination compared to SIRT alone in unresectable HCC: A promising approach for improved survival. Clin Res Hepatol Gastroenterol. 2024; 48(2):102282. doi: 10.1016/j.clinre.2024.102282

[90] Yeo YH, Liang J, Lauzon M, et al. Immunotherapy and transarterial radioembolization combination treatment for advanced hepatocellular carcinoma. Am J Gastroenterol. 2023; 118(12):2201-2211. doi: 10.14309/ajg.0000000000002467

[91] Garcia-Reyes K, Gottlieb RA, Menon KM, et al. Radioembolization plus immune checkpoint inhibitor therapy compared with radioembolization plus tyrosine kinase inhibitor therapy for the treatment of hepatocellular carcinoma. J Vasc Interv Radiol. 2024; 35(5):722-730.e1. doi: 10.1016/j.jvir.2024.02.004