REFERENCES
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-63.
2. Liu CJ, Chen PJ. Changing epidemiology of liver disease in Asia: dual infection of HBV and HCV. Liver Int. 2022;42:1945-54.
3. Ioannou GN. Epidemiology and risk-stratification of NAFLD-associated HCC. J Hepatol. 2021;75:1476-84.
4. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400:1345-62.
5. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82:315-74.
6. Taddei TH, Brown DB, Yarchoan M, Mendiratta-Lala M, Llovet JM. Critical update: AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2025;82:272-4.
7. Vogel A, Chan SL, Dawson LA, et al. ; ESMO Guidelines Committee. Electronic address: [email protected]. Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025;36:491-506.
8. Pinato DJ, Murray SM, Forner A, et al. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021;9:e003311.
9. Tan J, Fan W, Liu T, et al. TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma. J Hepatol. 2023;79:126-40.
10. Wang Z, Li Q, Liang B. Hypoxia as a target for combination with transarterial chemoembolization in hepatocellular carcinoma. Pharmaceuticals. 2024;17:1057.
11. Romero D. Early promising results with addition of an ICI and an anti-angiogenic to TACE. Nat Rev Clin Oncol. 2025;22:157.
12. Sangro B, Kudo M, Erinjeri JP, et al. ; EMERALD-1 Investigators. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study. Lancet. 2025;405:216-32.
13. Kudo M, Ren Z, Guo Y, et al. ; LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2025;405:203-15.
14. Dong J, Han G, Ogasawara S, et al. LBA2 TALENTACE: a phase III, open-label, randomized study of on-demand transarterial chemoembolization (TACE) combined with atezolizumab + bevacizumab (Atezo+Bev) or on-demand TACE alone in patients with systemically untreated, intermediate-to-high burden unresectable hepatocellular carcinoma (uHCC). Ann Oncol. 2025;36:S62.
15. Zhu H, Teng G, Fan W, et al. Transarterial chemoembolization (TACE) combined with camrelizumab and apatinib versus TACE alone in the treatment of unresectable hepatocellular carcinoma eligible for embolization: a multicenter, open-label, randomized, phase 2 study (CAP-ACE). JCO. 2025;43:LBA522.
16. Zhou J, Sun H, Wang Z, et al. China liver cancer guidelines for the diagnosis and treatment of hepatocellular carcinoma (2024 Edition). Liver Cancer. 2025;14:779-835.
17. Li C, Chen L, Bao H, Wang Y, Zhu G. Synergistic era: Practice and reflection on TACE combined with systemic therapy in hepatocellular carcinoma. SciEriXiv. 2025.
18. Matsui O, Kobayashi S, Sanada J, et al. Hepatocelluar nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis. Abdom Imaging. 2011;36:264-72.
19. Goldstein HM, Wallace S, Anderson JH, Bree RL, Gianturco C. Transcatheter occlusion of abdominal tumors. Radiology. 1976;120:539-45.
20. Nakamura H, Hashimoto T, Oi H, Sawada S. Transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology. 1989;170:783-6.
21. Llovet JM, Real MI, Montaña X, et al. ; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734-9.
22. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164-71.
23. Zhu HD, Liu R, Jia ZZ, et al. Transarterial chemoembolization for hepatocellular carcinoma: treatment algorithm proposed by Chinese College of Interventionalists(CCI). EngMedicine. 2024;1:1-9.
24. Miyayama S, Matsui O. Superselective conventional transarterial chemoembolization for hepatocellular carcinoma: rationale, technique, and outcome. J Vasc Interv Radiol. 2016;27:1269-78.
25. de Baere T, Ronot M, Chung JW, et al. Initiative on superselective conventional transarterial chemoembolization results (INSPIRE). Cardiovasc Intervent Radiol. 2022;45:1430-40.
26. Liu B, Gao S, Guo J, et al. Efficacy and safety of hepasphere drug-eluting bead transarterial chemoembolization combined with hepatic arterial infusion chemotherapy as the second-line treatment in advanced hepatocellular carcinoma. J Hepatocell Carcinoma. 2024;11:477-88.
27. Gjoreski A, Popova-Jovanovska R, Eftimovska-Rogac I, Vejseli J. Safety profile and efficacy of chemoembolization with doxorubicin - loaded polyethylene glycol microspheres in patients with hepatocellular carcinoma. Open Access Maced J Med Sci. 2019;7:742-6.
28. Lin CY, Liu YS, Pan KT, Chen CB, Hung CF, Chou CT. The short-term safety and efficacy of TANDEM microspheres of various sizes and doxorubicin loading concentrations for hepatocellular carcinoma treatment. Sci Rep. 2021;11:12277.
29. Vogl TJ, Lammer J, Lencioni R, et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011;197:W562-70.
30. Ayyub J, Dabhi KN, Gohil NV, et al. Evaluation of the safety and efficacy of conventional transarterial chemoembolization (cTACE) and drug-eluting bead (DEB)-TACE in the management of unresectable hepatocellular carcinoma: a systematic review. Cureus. 2023;15:e41943.
31. Shi D, Ren Y, Liu Y, et al. Temperature-sensitive nanogels combined with polyphosphate and cisplatin for the enhancement of tumor artery embolization by coagulation activation. Acta Biomater. 2024;185:240-53.
32. Li Q, Shi J, Ruan X, et al. Hypoxia‐ and pH‐responsive metal‐phenolic network‐engineered ferroptosis‐immuno microspheres for transarterial chemoembolization in hepatocellular carcinoma. Adv Funct Mater. 2025;35:e10798.
33. Wen K, Ren Y, Huang J, et al. Dual-stage drug delivery microspheres amplify tumor starvation through coagulation-enhanced vascular occlusion. Small. 2025;21:e08070.
34. Zhang M, Zhou J, Jiang X, et al. MoS2 nanozyme-chlorella hydrogels: pioneering a hepatocellular carcinoma integrative therapy. Adv Funct Mater. 2025;35:2417125.
35. Xu J, Pei Z, Wang Y, et al. Bioactive microspheres to enhance sonodynamic-embolization-metalloimmune therapy for orthotopic liver cancer. Biomaterials. 2025;317:123063.
36. Yang N, Sun X, Zhou Y, et al. Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy. Sci Bull. 2023;68:1772-83.
37. Llovet JM, Ricci S, Mazzaferro V, et al. ; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-90.
38. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163-73.
39. Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res. 2008;14:5459-65.
40. Li X, Qiu M, Wang S, Zhu H, Feng B, Zheng L. A phase I dose-escalation, pharmacokinetics and food-effect study of oral donafenib in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2020;85:593-604.
41. 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;23:77-90.
42. 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;76:862-73.
43. Rimassa L, Chan SL, Sangro B, et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. J Hepatol. 2025;83:899-908.
44. Yau T, Galle PR, Decaens T, et al. ; CheckMate 9DW investigators. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025;405:1851-64.
45. Ren Z, Xu J, Bai Y, et al. ; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021;22:977-90.
46. Qin S, Kudo M, Meyer T, et al. Tislelizumab vs sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a phase 3 randomized clinical trial. JAMA Oncol. 2023;9:1651-9.
47. Qin S, Gu S, Chan SL, et al. ; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study. Lancet Oncol. 2025;26:1598-611.
48. Zhao C, Zhang Y, Wang G, et al. Finotonlimab (PD-1 inhibitor) plus bevacizumab (bevacizumab biosimilar) as first-tier therapy for late-stage hepatocellular carcinoma: a randomized phase 2/3 trial. Signal Transduct Target Ther. 2025;10:249.
49. Shi Y, Han G, Zhou J, et al. Toripalimab plus bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HEPATORCH): a randomised, open-label, phase 3 trial. Lancet Gastroenterol Hepatol. 2025;10:658-70.
50. Strebel BM, Dufour JF. Combined approach to hepatocellular carcinoma: a new treatment concept for nonresectable disease. Expert Rev Anticancer Ther. 2008;8:1743-9.
51. Kudo M, Imanaka K, Chida N, et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011;47:2117-27.
52. 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;64:1090-8.
53. 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;2:565-75.
54. Kudo M, Ueshima K, Ikeda M, et al. Final results of TACTICS: a randomized, prospective trial comparing transarterial chemoembolization plus sorafenib to transarterial chemoembolization alone in patients with unresectable hepatocellular carcinoma. Liver Cancer. 2022;11:354-67.
55. Duan X, Li H, Kuang D, et al. Comparison of drug-eluting bead transarterial chemoembolization combined with apatinib versus drug-eluting bead transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: a randomized, prospective, multicenter phase III trial. Signal Transduct Target Ther. 2024;9:304.
56. Peng Z, Fan W, Zhu B, et al. Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma: a phase III, randomized clinical trial (LAUNCH). J Clin Oncol. 2023;41:117-27.
57. Koroki K, Ogasawara S, Ooka Y, et al. Analyses of intermediate-stage hepatocellular carcinoma patients receiving transarterial chemoembolization prior to designing clinical trials. Liver Cancer. 2020;9:596-612.
58. Zhu HD, Li HL, Huang MS, et al. ; CHANCE001 Investigators. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Signal Transduct Target Ther. 2023;8:58.
59. Jin ZC, Chen JJ, Zhu XL, et al. ; CHANCE2201 Investigators. Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study. EClinicalMedicine. 2024;72:102622.
60. Liu K, Yang L, Zhang X-M, et al. HIF-1α and VEGF levels for monitoring hepatocellular carcinoma treatment response to transcatheter arterial chemoembolization. Transl Cancer Res. 2017;6:1043-9.
