Neoadjuvant treatment strategies for hepatocellular carcinoma

Table 1 Prognostic comparison of patients with neoadjuvant therapy and those with initial resectable or transplantable hepatocellular carcinoma

Year	Study design	Neoadjuvant group						Resectable or transplantable group			Ref.
		Neoadjuvant therapy	Times of neoadjuvant therapy	Tumor condition	Success rate	Subsequent therapy	Prognosis	Tumor condition	Tumor treatment	Prognosis
2017	Retrospective study	DEB-TACE	1.38	Within Milan criteria 88%	89.0%	OLT	3-yr OS: 79%; 3-yr DFS: 79%	Within Milan criteria 77%	OLT	3-yr OS: 73.0%; 3-yr DFS: 70.0%	[29]
2015	Retrospective study	TACE	NA	Over 10 cm	28.4%	LR/OLT	1-yr OS: 76.5%	HCC over 10 cm	BSC	1-yr OS: 3.7%	[27]
2019	Retrospective study	TACE, RFA; TACE + RFA	NA	Within Milan criteria 56.7%	25.2%	LT	Downstage: 5-yer DFS: 86%; No downstage: 5-yr DFS: 71.5%	Within Milan criteria 68.4%	LT	5-yr DFS: 83.0%	[30]
2013	Retrospective study	TACE, RFA; HIFU, etc.	1.6 ± 0.4	Outside Milan criteria	NA	LT	5-yr OS: 70.7%	Within Milan criteria	LT	5-yr OS: 74.1%	[14]
2015	Retrospective study	TACE, RFA	NA	Outside UNOS T2 criteria	65.3%	LT	5-yr OS: 77.8%; 5-yr DFS: 90.8%	Within UNOS T2 criteria	LT	5-yr OS: 81.0%; 5-yr DFS: 88.0%	[41]
2019	Retrospective study	TACE, RFA; SIRT, etc.	NA	Outside Milan criteria	45.2%	LT	5-yr OS: 76.0%; 5-yr DFS: 89.0%	Within Milan criteria	LT	5-yr OS: 81.0%; 5-yr DFS: 98.3%	[42]
2017	Retrospective study	TACE, RFA; Sorafenib	NA	Outside Milan criteria	26.7%	OLT	NA, comparable with those within Milan criteria	Within Milan criteria	OLT	NA	[43]
2015	Retrospective study	TACE, RFA	NA	Outside Milan criteria	36.4%	LT	5-yr RFS: 81.8%	Within Milan criteria	LT	5-yr RFS: 94.6%	[44]
2019	Retrospective study	NA	NA	Outside Milan criteria	68.4%	LT	5-yr OS: 63.0%	Within Milan criteria	LT	5-yr OS: 77.0%	[45]

DEB-TACE: Drug-eluting beads transarterial chemoembolization; TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation; HIFU: High intensity focused ultrasound; OLT: Orthotopic liver transplantation; LT: Liver transplantation; OS: Overall survival; DFS: Disease-free survival; RFS: Recurrence-free survival: UNOS: United Network for Organ Sharing; NA: Not available; LR: Liver resection; SIRT: Selective interval radiation therapy; HCC: Hepatocellular carcinoma; BSC: Best supportive care.

Table 2 Summary of pre-transplant transarterial chemoembolization and trans-arterial radioembolization in downstage treatment for hepatocellular carcinoma

Year	Neoadjuvant treatment	Entry criteria	Success downstage rate	Subsequent therapy	Adverse events	Incidence rate	Ref.
2015	Conventional TACE; I131 Metuximab TACE	Patients within USCF criteria	NA	OLT	Hepatic artery thrombosis hepatic aneurysm	1.5%	[89]
2015	DEB-TACE	BCLC 0/A/B stage	26.7%	OLT	Grade 3/4	3.2%	[102]
2017	TACE		NA	OLT	Hepatic artery thrombosisRetransplant	27%22.7%	[90]
2020	DEB-TACE	AJCC stage ≤ T3a	73.3%	OLT	Grade 3Grade 4	3.1%0.0%	[86]
2006	Y-90 RE	UNOS stage T3	66.0%	OLT	NA	NA	[103]
2017	Y-90 RE	BCLC A/B/C stage	78.9%	OLT	NA	NA	[104]
2011	Y-90 RE	UNOS stage T2, T3, T4a	50.0%	OLT	Hyperbilirubinemia (Grade3)	13.0%	[105]
2013	Y-90 RE	UNOS stage T3, T4a	33.0%	OLT	NA	NA	[95]
2021	Y-90 RE	UNOS stage T1, T2, T3, T4	43.0%	OLT	NA	NA	[96]

DEB-TACE: Drug-eluting beads transarterial chemoembolization; TACE: Transarterial chemoembolization; Y-90 RE: Yttrium-90 radioembolization; UCSF: University of California, San Francisco; BCLC: Barcelona Clinic Liver Cancer; AJCC: American Joint Committee on Cancer; UNOS: United Network for Organ Sharing; NA: Not available; I¹³¹: Iodine-131; OLT: Orthotopic liver transplantation.