Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: Where do we stand?

Table 2 Studies of neo-adjuvant therapy for down-staging hepatocellular carcinoma before liver transplant

Ref.	Year	n	LRT	Inclusion criteria for DS protocol	Successful DS criteria	Mandatory waiting time prior to LT (mo)	The role of AFP	DS rate	LT (patients)	Waiting time to LT (mo)	Patient survival after LT	Recurrence-free survival after LT
Transarterial therapy alone
Otto et al[25]	2006	62	TACE	Beyond MC	30% decrease in size	No	NA	55%	27	5.9	73%	68% at 5 yr
										(1.9-19.3)	at 5 yr
Chapman et al[28]	2008	76	TACE	Beyond MC	MC	3-4	NA	24%	17	5.8 ± 3.5	94%	100%, 50%
											at 5 yr	at 3, 5 yr
De Luna et al[32]	2009	27	TACI	Beyond MC	MC	No	Not significant	63%	15	10.9	79%	NA
										(0.7-114.1)	at 3 yr
Multimodal approach
Yao et al[6]	2008	61	TACE, RFA,	One lesion, 5-8 cm	MC for DDLT	3	AFP > 1000 ng/mL	71%	35	8.2 (3-25)	92%	92%
			Resection	2-3 lesions, 3-5 cm,	UCSF criteria for LDLT		Predicts DS failure				at 2 yr	at 2 yr
				total diameter ≤ 8 cm
				4-5 lesions, ≤ 3 cm,
				total diameter ≤ 8 cm
Ravaioli et al[8]	2008	48	TACE, RFA	One lesion, 5-6 cm	MC and AFP ≤ 400 ng/mL	3	AFP ≤ 400 ng/mL, listing criteria	67%	32	6	NA	78%, 71%
			PEI, resection	2 lesions 3-5 cm			AFP > 30 ng/mL, predictor of recurrence after LT					at 1, 3 yr
				3-5 lesions, ≤ 4 cm, total diameter ≤ 12 cm
Barakat et al[44]	2010	32	TACE, RFA,	Beyond MC	MC	No	Failed vs successful DS	56%	14	11.2	92%, 75%	2 patients
			TARE, resection				5670 ng/mL vs 799 ng/mL			(4.4-22.6)	at 1, 2 yr	Recurrence

HCC: Hepatocellular carcinoma; LRT: Locoreginal therapy; DS: Down-stage; LT: Liver transplant; AFP: Alpha-fetoprotein; TACE: Transarterial chemoembolization; MC: Milan criteria; TACI: Transarterial chemo-infusion; RFA: Radiofrequency ablation; UCSF: University of California at San Francisco; PEI: Percutaneous ethanol injection; NA: Not available.