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Finn RS, Qin S, Ikeda M, <i>et al<\/i>. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020; 382:1894-1905.","DOI":"10.1056\/NEJMoa1915745"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Cheng AL, Qin S, Ikeda M, <i>et al<\/i>. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab <i>vs.<\/i> sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022; 76:862-873.","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Abou-Alfa GK, Lau G, Kudo M, <i>et al<\/i>. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022; 1:EVIDoa2100070.","DOI":"10.1056\/EVIDoa2100070"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Qin S, Chan SL, Gu S, <i>et al<\/i>. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): A randomised, open-label, international phase 3 study. Lancet. 2023; 402:1133-1146.","DOI":"10.1016\/S0140-6736(23)00961-3"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Kelley RK, Rimassa L, Cheng AL, <i>et al<\/i>. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022; 23:995-1008.","DOI":"10.1016\/S1470-2045(22)00326-6"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Zhu XD, Huang C, Shen YH, Xu B, Ge NL, Ji Y, Qu XD, Chen L, Chen Y, Li ML, Zhu JJ, Tang ZY, Zhou J, Fan J, Sun HC. Hepatectomy after conversion therapy using tyrosine kinase inhibitors plus anti-PD-1 antibody therapy for patients with unresectable hepatocellular carcinoma. Ann Surg Oncol. 2023; 30:2782-2790.","DOI":"10.1245\/s10434-022-12530-z"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Zhang W, Hu B, Han J, <i>et al<\/i>. Surgery after conversion therapy with PD-1 inhibitors plus tyrosine kinase inhibitors are effective and safe for advanced hepatocellular carcinoma: A pilot study of ten patients. Front Oncol. 2021; 11:747950.","DOI":"10.3389\/fonc.2021.747950"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Kaneko S, Tsuchiya K, Yasui Y, <i>et al<\/i>. Conversion surgery for hepatocellular carcinoma after tyrosine kinase inhibitor treatment. JGH Open. 2022; 6:301-308.","DOI":"10.1002\/jgh3.12735"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Hakoda H, Ichida A, Hasegawa K. Advances in systemic therapy leading to conversion surgery for advanced hepatocellular carcinoma. Biosci Trends. 2025; 18:525-534.","DOI":"10.5582\/bst.2024.01372"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Iseda N, Itoh S, Toshima T, <i>et al<\/i>. Outcome of hepatectomy after systemic therapy for hepatocellular carcinoma: A Japanese multicenter study. Surg Today. 2025; 55:510-517.","DOI":"10.1007\/s00595-024-02930-x"},{"key":"11","unstructured":"11. Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of the Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, Liver Study Group of the Surgery Committee of the Beijing Medical Association. Expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition). Zhonghua Wai Ke Za Zhi. 2024; 62:984-995."},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Ma YN, Jiang X, Liu H, Song P, Tang W. Conversion therapy for initially unresectable hepatocellular carcinoma: Current status and prospects. Biosci Trends. 2024; 17:415-426.","DOI":"10.5582\/bst.2023.01322"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Tang H, Cao Y, Jian Y, Li X, Li J, Zhang W, Wan T, Liu Z, Tang W, Lu S. Conversion therapy with an immune checkpoint inhibitor and an antiangiogenic drug for advanced hepatocellular carcinoma: A review. Biosci Trends. 2022; 16:130-141.","DOI":"10.5582\/bst.2022.01019"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Akahoshi K, Shindoh J, Tanabe M, <i>et al<\/i>. Oncological resectability criteria for hepatocellular carcinoma in the era of novel systemic therapies: The Japan Liver Cancer Association and Japanese Society of Hepato-Biliary-Pancreatic Surgery Expert Consensus Statement 2023. Liver Cancer. 2024; 13:1-10.","DOI":"10.1159\/000538627"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Reig M, Forner A, Rimola J, <i>et al<\/i>. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022; 76:681-693.","DOI":"10.1016\/j.jhep.2021.11.018"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Omata M, Cheng AL, Kokudo N, <i>et al<\/i>. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int. 2017; 11:317-370.","DOI":"10.1007\/s12072-017-9799-9"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Kudo M, Kawamura Y, Hasegawa K, <i>et al<\/i>. Management of hepatocellular carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer. 2021; 10:181-223.","DOI":"10.1159\/000514174"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Yoh T, Ishii T, Nishio T, Koyama Y, Ogiso S, Fukumitsu K, Uchida Y, Ito T, Seo S, Hata K, Hatano E. A conceptual classification of resectability for hepatocellular carcinoma. World J Surg. 2023; 47:740-748.","DOI":"10.1007\/s00268-022-06803-7"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Nakamura I, Yoh T, Nishimura T, Okuno M, Okamoto T, Sueoka H, Iida K, Tada M, Ishii T, Seo S, Fujimoto Y, Iijima H, Hirono S, Hatano E. A classification model for resectability in hepatocellular carcinoma patients. Hepatol Res. 2024; 54:818-829.","DOI":"10.1111\/hepr.14108"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Sun HC, Zhou J, Wang Z, <i>et al<\/i>. Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition). Hepatobiliary Surg Nutr. 2022; 11:227-252.","DOI":"10.21037\/hbsn-21-328"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007; 356:1545-1559.","DOI":"10.1056\/NEJMra065156"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Shindoh J, Tzeng CW, Aloia TA, Curley SA, Zimmitti G, Wei SH, Huang SY, Gupta S, Wallace MJ, Vauthey JN. Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival. Br J Surg. 2013; 100:1777-1783.","DOI":"10.1002\/bjs.9317"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Johnson PJ, Berhane S, Kagebayashi C, <i>et al<\/i>. Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach-The ALBI grade. J Clin Oncol. 2015; 33:550-558.","DOI":"10.1200\/JCO.2014.57.9151"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Makuuchi M, Kosuge T, Takayama T, Yamazaki S, Kakazu T, Miyagawa S, Kawasaki S. Surgery for small liver cancers. Semin Surg Oncol. 1993; 9:298-304.","DOI":"10.1002\/ssu.2980090404"},{"key":"25","unstructured":"25. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69:182-236."},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Kudo M, Finn RS, Qin S, <i>et al<\/i>. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet. 2018; 391:1163-1173.","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Ren Z, Xu J, Bai Y, <i>et al<\/i>. 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; 22:977-990.","DOI":"10.1016\/S1470-2045(21)00252-7"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Qin S, Kudo M, Meyer T, <i>et al<\/i>. Tislelizumab vs sorafenib as first-line treatment for unresectable hepatocellular carcinoma: A phase 3 randomized clinical trial. JAMA Oncol. 2023; 9:1651-1660.","DOI":"10.1001\/jamaoncol.2023.4003"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Shimose S, Saeki I, Ito T, <i>et al<\/i>. The benefit of conversion therapy for patients with unresectable hepatocellular carcinoma receiving atezolizumab plus bevacizumab using newly established oncological resectability criteria in Japan. Hepatol Int. 2025; 19:846-855.","DOI":"10.1007\/s12072-025-10781-y"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Kudo M. Atezolizumab plus bevacizumab followed by curative conversion (ABC conversion) in patients with unresectable, TACE-unsuitable intermediate-stage hepatocellular carcinoma. Liver Cancer. 2022; 11:399-406.","DOI":"10.1159\/000526163"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Llovet JM, Ricci S, Mazzaferro V, <i>et al<\/i>. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359:378-390.","DOI":"10.1056\/NEJMoa0708857"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Zhu XD, Huang C, Shen YH, Ji Y, Ge NL, Qu XD, Chen L, Shi WK, Li ML, Zhu JJ, Tan CJ, Tang ZY, Zhou J, Fan J, Sun HC. Downstaging and resection of initially unresectable hepatocellular carcinoma with tyrosine kinase inhibitor and anti-PD-1 antibody combinations. Liver Cancer. 2021; 10:320-329.","DOI":"10.1159\/000514313"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Ichida A, Arita J, Hatano E, <i>et al<\/i>. A multicenter phase 2 trial evaluating the efficacy and safety of preoperative lenvatinib therapy for patients with advanced hepatocellular carcinoma (LENS-HCC Trial). Liver Cancer. 2024; 13:322-334.","DOI":"10.1159\/000535514"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Kudo M, Aoki T, Ueshima K, <i>et al<\/i>. Achievement of complete response and drug-free status by atezolizumab plus bevacizumab combined with or without curative conversion in patients with transarterial chemoembolization-unsuitable, intermediate-stage hepatocellular carcinoma: A multicenter proof-of-concept study. Liver Cancer. 2023; 12:321-338.","DOI":"10.1159\/000529574"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Peng Z, Fan W, Zhu B, <i>et al<\/i>. Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma: A phase III, randomized clinical trial (LAUNCH). J Clin Oncol. 2023; 41:117-127.","DOI":"10.1200\/JCO.22.00392"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Kudo M, Ueshima K, Ikeda M, <i>et al<\/i>. Randomised, multicentre prospective t r i a l of t r a n s a r t e r i a l chemoembolisation plus sorafenib as compared with transarterial chemoembolisation alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020; 69:1492-1501.","DOI":"10.1136\/gutjnl-2019-318934"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Itoh S, Toshida K, Morita K, Kurihara T, Nagao Y, Tomino T, Toshima T, Harada N, Mori M, Yoshizumi T. Clinical effectiveness of surgical treatment after lenvatinib administration for hepatocellular carcinoma. Int J Clin Oncol. 2022; 27:1725-1732.","DOI":"10.1007\/s10147-022-02229-2"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Shindoh J, Kawamura Y, Kobayashi M, Akuta N, Okubo S, Matsumura M, Suzuki Y, Hashimoto M. Prognostic advantages of individual additional interventions after lenvatinib therapy in patients with advanced hepatocellular carcinoma. J Gastrointest Surg. 2022; 26:1637-1646.","DOI":"10.1007\/s11605-022-05388-9"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Hidaka M, Hara T, Soyama A, Sasaki R, Matsushima H, Tanaka T, Hamada T, Imamura H, Adachi T, Kanetaka K, Miyaaki H, Okano S, Eguchi S. The outcome of conversion liver resection surgery by lenvatinib treatment: A single center experience. Anticancer Res. 2022; 42:3049-3054.","DOI":"10.21873\/anticanres.15791"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Yoshimoto T, Imura S, Morine Y, Ikemoto T, Arakawa Y, Iwahashi S, Saito YU, Takasu C, Ishikawa D, Teraoku H, Bando Y, Shimada M. The outcome of sorafenib therapy on unresectable hepatocellular carcinoma: Experience of conversion and salvage hepatectomy. Anticancer Res. 2018; 38:501-507.","DOI":"10.21873\/anticanres.12250"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Kudo M. A New treatment option for intermediate-stage hepatocellular carcinoma with high tumor burden: Initial Lenvatinib therapy with subsequent selective TACE. Liver Cancer. 2019; 8:299-311.","DOI":"10.1159\/000502905"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. He M, Li Q, Zou R, <i>et al<\/i>. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: A randomized clinical trial. JAMA Oncol. 2019; 5:953-960.","DOI":"10.1001\/jamaoncol.2019.0250"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Lyu N, Wang X, Li JB, Lai JF, Chen QF, Li SL, Deng HJ, He M, Mu LW, Zhao M. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase III trial (FOHAIC-1). J Clin Oncol. 2022; 40:468-480.","DOI":"10.1200\/JCO.21.01963"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Li QJ, He MK, Chen HW, Fang WQ, Zhou YM, Xu L, Wei W, Zhang YJ, Guo Y, Guo RP, Chen MS, Shi M. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: A randomized phase III trial. J Clin Oncol. 2022; 40:150-160.","DOI":"10.1200\/JCO.21.00608"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Kudo M, Ueshima K, Chan S, <i>et al<\/i>. Lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and Child-Pugh A liver function: A proof-of-concept study. Cancers (Basel). 2019; 11:1084.","DOI":"10.3390\/cancers11081084"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Zhang N, Liu K, Yu Y, <i>et al<\/i>. Efficacy and safety of atezolizumab and bevacizumab with or without TACE as first-line therapy for unresectable HCC: A multicenter cohort study. Hepatol Int. 2025; 19:1382-1396.","DOI":"10.1007\/s12072-025-10895-3"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. Kudo M, Han KH, Ye SL, Zhou J, Huang YH, Lin SM, Wang CK, Ikeda M, Chan SL, Choo SP, Miyayama S, Cheng AL. A changing paradigm for the treatment of intermediate-stage hepatocellular carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements. Liver Cancer. 2020; 9:245-260.","DOI":"10.1159\/000507370"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Eisenhauer EA, Therasse P, Bogaerts J, <i>et al<\/i>. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45:228-247.","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010; 30:52-60.","DOI":"10.1055\/s-0030-1247132"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50. Huang C, Zhu XD, Shen YH, <i>et al<\/i>. Radiographic and \u03b1-fetoprotein response predict pathologic complete response to immunotherapy plus a TKI in hepatocellular carcinoma: A multicenter study. BMC Cancer. 2023; 23:416.","DOI":"10.1186\/s12885-023-10898-z"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51. Takeyama H, Beppu T, Higashi T, <i>et al<\/i>. Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma. Surg Today. 2018; 48:431-438.","DOI":"10.1007\/s00595-017-1603-x"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52. Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. J Hepatobiliary Pancreat Sci. 2022; 29:732-740.","DOI":"10.1002\/jhbp.1135"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53. Long Y, Huang J, Liao J, Zhang D, Huang Z, He X, Zhang L. Safety and survival outcomes of liver resection following triple combination conversion therapy for initially unresectable hepatocellular carcinoma. Cancers (Basel). 2023; 15:5878.","DOI":"10.3390\/cancers15245878"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54. Zhang J, Zhang X, Mu H, Yu G, Xing W, Wang L, Zhang T. Surgical conversion for initially unresectable locally advanced hepatocellular carcinoma using a triple combination of angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy: A retrospective study. Front Oncol. 2021; 11:729764.","DOI":"10.3389\/fonc.2021.729764"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55. Jia J, Ding C, Mao M, Gao F, Shao Z, Zhang M, Zheng S. Pathological complete response after conversion therapy in unresectable hepatocellular carcinoma: A retrospective study. BMC Gastroenterol. 2024; 24:242.","DOI":"10.1186\/s12876-024-03298-5"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56. Sato S, Aoki T, Matsumoto T, Shiraki T, Mori S, Iso Y, Nemoto T, Onishi T, Iijima M, Ishida K. Pathological complete response of hepatocellular carcinoma confirmed by conversion hepatectomy following atezolizumab plus bevacizumab therapy: A case report and literature review. Clin J Gastroenterol. 2024; 17:292-299.","DOI":"10.1007\/s12328-023-01895-7"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57. Fukunaga A, Takata K, Itoh S, Yamauchi R, Tanaka T, Yokoyama K, Shakado S, Kohashi K, Yoshizumi T, Hirai F. Complete tumor necrosis confirmed by conversion hepatectomy after atezolizumab-bevacizumab treatment for advanced-stage hepatocellular carcinoma with lung metastasis. Clin J Gastroenterol. 2023; 16:224-228.","DOI":"10.1007\/s12328-022-01744-z"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58. Hidaka Y, Tomita M, Desaki R, Hamanoue M, Takao S, Kirishima M, Ohtsuka T. Conversion surgery for hepatocellular carcinoma with portal vein tumor thrombus after successful atezolizumab plus bevacizumab therapy: A case report. World J Surg Oncol. 2022; 20:228.","DOI":"10.1186\/s12957-022-02691-2"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59. Chi QY, Gao XD, Wang M, Liu QY, Zeng YY, Yang LF, Liu ZJ, Wang SJ, Weng SG, Zhang ZB. Prognostic value of pathological response after conversion therapy and salvage surgery in unresectable hepatocellular carcinoma. Liver Int. 2026; 46:e70681.","DOI":"10.1111\/liv.70681"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60. Wang MD, Xu XJ, Wang KC, Diao YK, Xu JH, Gu LH, Yao LQ, Li C, Lv GY, Yang T. Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities. Cancer Sci. 2024; 115:2159-2169.","DOI":"10.1111\/cas.16194"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61. Luo L, He Y, Zhu G, Xiao Y, Song S, Ge X, Wang T, Xie J, Deng W, Hu Z, Shan R. Hepatectomy after conversion therapy for initially unresectable HCC: What is the difference? J Hepatocell Carcinoma. 2022; 9:1353-1368.","DOI":"10.2147\/JHC.S388965"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62. Yamamura K, Beppu T, Miyata T, Okabe H, Nitta H, Imai K, Hayashi H, Akahoshi S. Conversion surgery for hepatocellular carcinoma following molecular therapy. Anticancer Res. 2022; 42:35-44.","DOI":"10.21873\/anticanres.15454"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63. Goto Y, Hisaka T, Sakai H, Takagi K, Fukutomi S, Akagi Y, Okuda K. Salvage surgery for initially unresectable locally advanced hepatocellular carcinoma downstaged by hepatic arterial infusion chemotherapy. Anticancer Res. 2020; 40:4773-4777.","DOI":"10.21873\/anticanres.14479"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64. Lu JF, Bruno R, Eppler S, Novotny W, Lum B, Gaudreault J. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008; 62:779-786.","DOI":"10.1007\/s00280-007-0664-8"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65. Sharma K, Marcus JR. Bevacizumab and wound-healing complications: mechanisms of action, clinical evidence, and management recommendations for the plastic surgeon. Ann Plast Surg. 2013; 71:434-440.","DOI":"10.1097\/SAP.0b013e31824e5e57"},{"key":"66","doi-asserted-by":"crossref","unstructured":"66. Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, Kudo M, Ku Y, Sakamoto M, Nakashima O, Kaneko S, Kokudo N, Liver Cancer Study Group of Japan. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol. 2016; 65:938-943.","DOI":"10.1016\/j.jhep.2016.05.044"},{"key":"67","unstructured":"67. Genentech. Avastin (bevacizumab) full prescribing information. <i>https:\/\/www.gene.com\/download\/pdf\/avastin_prescribing.pdf<\/i> (accessed August 25, 2026)."},{"key":"68","unstructured":"68. European Medicines Agency. Avastin: EPAR product information. <i>https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/avastin-epar-product-information_en.pdf<\/i> (accessed August 25, 2026)."},{"key":"69","doi-asserted-by":"crossref","unstructured":"69. Yopp A, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Cha E, Hack SP, Lian Q, Spahn J, Wu C, Qin S, Chow PK. Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk hepatocellular carcinoma. J Hepatol. 2026; 84:1102-1111.","DOI":"10.1016\/j.jhep.2026.01.006"},{"key":"70","doi-asserted-by":"crossref","unstructured":"70. Aoki T, Kudo M, Nishida N, <i>et al<\/i>. Proposal of discontinuation criteria of atezolizumab plus bevacizumab after curative conversion therapy for unresectable early-to-intermediate-stage hepatocellular carcinoma: A multicenter proof-of-concept study. J Gastroenterol. 2025; 60:738-753.","DOI":"10.1007\/s00535-025-02233-z"},{"key":"71","doi-asserted-by":"crossref","unstructured":"71. Zhang X, Zhu X, Zhong J, <i>et al<\/i>. Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: A multicenter retrospective study. Sci Rep. 2024; 14:9745.","DOI":"10.1038\/s41598-024-60379-x"},{"key":"72","doi-asserted-by":"crossref","unstructured":"72. Yang DL, Peng N, Nong JL, <i>et al<\/i>. Survival benefit of hepatectomy after complete or partial response to conversion therapy in unresectable hepatocellular carcinoma (GUIDANCE003): A multicenter study. Liver Cancer. 2025; 14:687-703.","DOI":"10.1159\/000546052"},{"key":"73","doi-asserted-by":"crossref","unstructured":"73. Sun HC, Zhu XD, Shen F, <i>et al<\/i>. Liver resection after atezolizumab and bevacizumab versus maintenance therapy for locally advanced hepatocellular carcinoma (TALENTOP): A multicentre, open-label, randomised, phase 3 trial. Lancet. 2026; 408:699-710.","DOI":"10.1016\/S0140-6736(26)01252-3"},{"key":"74","doi-asserted-by":"crossref","unstructured":"74. Hern\u00e1n MA, Sauer BC, Hern\u00e1ndez-D\u00edaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016; 79:70-75.","DOI":"10.1016\/j.jclinepi.2016.04.014"},{"key":"75","doi-asserted-by":"crossref","unstructured":"75. Agarwal P, Moshier E, Ru M, Ohri N, Ennis R, Rosenzweig K, Mazumdar M. Immortal time bias in observational studies of time-to-event outcomes: Assessing effects of postmastectomy radiation therapy using the National Cancer Database. Cancer Control. 2018; 25:1073274818789355.","DOI":"10.1177\/1073274818789355"},{"key":"76","doi-asserted-by":"crossref","unstructured":"76. Hern\u00e1n MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol. 2016; 183:758-764.","DOI":"10.1093\/aje\/kwv254"},{"key":"77","doi-asserted-by":"crossref","unstructured":"77. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2008; 167:492-499.","DOI":"10.1093\/aje\/kwm324"},{"key":"78","doi-asserted-by":"crossref","unstructured":"78. Sterne JA, Hern\u00e1n MA, Reeves BC, <i>et al<\/i>. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355:i4919.","DOI":"10.1136\/bmj.i4919"},{"key":"79","doi-asserted-by":"crossref","unstructured":"79. Yadav K, Lewis RJ. Immortal Time Bias in Observational Studies. JAMA. 2021; 325:686-687.","DOI":"10.1001\/jama.2020.9151"},{"key":"80","doi-asserted-by":"crossref","unstructured":"80. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015; 34:3661-3679.","DOI":"10.1002\/sim.6607"},{"key":"81","doi-asserted-by":"crossref","unstructured":"81. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Sch\u00fcnemann HJ, GRADE Working Group. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 336:924-926.","DOI":"10.1136\/bmj.39489.470347.AD"},{"key":"82","unstructured":"82. Hern\u00e1n MA, Robins JM. Causal Inference: What If. 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