Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

Table 1 Baseline patient demographic and disease characteristics

Characteristics	Total, n = 99	DEB-TACE group, n = 45	Control group, n = 54	P value
Age in yr	52.6 ± 11.1	52.0 ± 12.1	53.0 ± 10.2	0.64
Sex				> 0.99
Male	92 (92.9)	42 (93.3)	50 (92.6)
Female	7 (7.1)	3 (6.7)	4 (7.4)
ECOG PS score				0.53
0	45 (45.5)	22 (48.9)	23 (42.6)
1	54 (54.5)	23 (51.1 )	31 (57.4)
HBV	99 (100.0)	45 (100.0)	54 (100.0)
Child­Pugh classification				< 0.01
A	83 (84.7)	43 (95.6)	40 (75.5)
B	11 (11.2)	2 (4.4)	9 (17.0)
C	4 (4.1)	0 (0.0)	4 (7.5)
Time to LT in month	1.0 (1.0, 2.0)	2.0 (1.0, 3.5)	1.0 (1.0, 1.0)	< 0.01
Macrovascular invasion				0.96
Negative	68 (68.7)	31 (68.9)	37 (68.5)
Segmental PVTT	31 (31.3)	14 (31.1)	17 (31.5)
AFP level at admission in ng/mL	94.7 (12.8, 3561.1)	275.1 (17.2, 5428.8)	43.1 (9.7, 455.2)	0.07
AFP level before LT in ng/mL	41.7 (8.0, 601.4)	41.7 (4.7, 619.7)	43.1 (9.7, 455.2)	0.61
AFP ≤ 400 ng/mL	74 (74.4)	32 (71.1)	42 (77.8)	0.44
AFP > 400 ng/mL	25 (25.3)	13 (28.9)	12 (22.2)
Overall diameter of target tumors in cm	8.0 (5.2, 11.3)	6.9 (4.7, 11.8)	8.0 (5.4, 11.0)	0.87
≤ 7 cm	46 (46.5)	24 (53.3)	22 (40.7)	0.21
> 7 cm	53 (53.5)	21 (46.7)	32 (59.3)
Tumor grade				0.97
Well differentiated	3 (3.0)	1 (2.2)	2 (3.7)
Moderately differentiated	71 (71.7)	33 (73.3)	38 (70.4)
Undifferentiated	25 (25.3)	11 (24.4)	14 (25.9)

Data are expressed as n (%) or mean ± SD. AFP: Alpha-fetoprotein; DEB-TACE: Drug-eluting bead transcatheter arterial chemoembolization; ECOG PS: Eastern Cooperative Oncology Group performance status; HBV: Hepatitis B virus; LT: Liver transplantation; PVTT: Portal vein tumor thrombus.

Table 2 Baseline subgroup disease characteristics

Characteristic	Without segmental PVTT		P value	With segmental PVTT		P value
	Group A, n = 31, 68.9%	Group C, n = 37, 68.5%		Group B, n = 14, 31.1%	Group D, n = 17, 31.5%
AFP level at admission in ng/mL	155.9 (11.9, 1386.6)	22.6 (7.2, 297.9)	0.121	5428.8 (33.5, 20000)	172.2 (54.5, 7951.4)	0.233
AFP level before LT in ng/mL	26.5 (4.6, 200.6)	22.6 (7.2, 297.9)	0.703	459.9 (4.6, 7670.5)	172.2 (54.5, 7951.4)	0.953
Overall diameter of target tumors in cm	6.3 (4.4, 9.6)	8.0 (4.9, 11.0)	0.449	9.4 (6.6, 16.6)	8.0 (6.1, 11.5)	0.361
Tumor grade, n (%)			0.925			> 0.99
Well differentiated	1 (3.2)	1 (2.7)		0 (0.0)	1 (5.9)
Moderately differentiated	22 (71.0)	27 (73.0)		11 (78.6)	11 (64.7)
Undifferentiated	8 (25.8)	9 (24.3)		3 (21.4)	5 (29.4)
MVI, n (%)			< 0.01			-
MVI = M0	13 (41.9)	11 (29.7)		-	-
MVI = M1	10 (32.3)	6 (16.2)		-	-
MVI = M2	8 (25.8)	20 (54.1)		-	-

AFP: Alpha-fetoprotein; LT: Liver transplantation; MVI: Microvascular invasion; PVTT: Portal vein tumor thrombus.

Table 3 Alpha-fetoprotein efficacy evaluation

Group	AFP before treatment	AFP after treatment	Z	P value
DEB-TACE group in ng/mL	275.1 (17.2-5428.8)	41.7 (4.7-619.7)	-3.810	< 0.001
Group A in ng/mL	155.9 (11.9, 1386.6)	26.5 (4.6, 200.6)	-2.793	0.005
Group B in ng/mL	5428.8 (33.5, 20000)	459.9 (4.6, 7670.5)	-2.341	0.019

AFP: Alpha-fetoprotein; DEB-TACE: Drug-eluting bead transarterial chemoembolization.

Table 4 Univariate and multivariate Cox proportional hazards model for recurrence-free survival and overall survival

Variable	Univariate analysis				Multivariate analysis
	Total, n	HR	95%CI	P value	HR	95%CI	P value
RFS
Pre-LT DEB-TACE as yes/no	45/54	2.62	1.41-4.89	0.002	2.73	1.44-5.14	0.002
Child-Pugh classification
A	83	Reference	N/A	N/A	N/A	N/A	N/A
B	12	2.03	0.98-4.23	0.056	N/A	N/A	N/A
C	4	1.52	0.36-6.35	0.559	N/A	N/A	N/A
Macrovascular invasion as yes/no	31/68	1.74	0.98-3.09	0.056	N/A	N/A	N/A
Overall diameter of target (tumors in cm for ≤ 7 cm/> 7 cm)	46/53	2.55	1.38-4.69	0.003	1.98	1.05-3.75	0.035
AFP of ≤ 400 ng/mL/> 400 ng/mL)	74/25	2.34	1.30-4.19	0.004	2.27	1.23-4.21	0.009
Tumor differentiation
Well differentiated	3	Reference	N/A	N/A	N/A	N/A	N/A
Moderately differentiated	71	1.42	0.19-10.45	0.726	N/A	N/A	N/A
Undifferentiated	25	2.27	0.30-17.13	0.426	N/A	N/A	N/A
OS
Pre-LT DEB-TACE as yes/no	45/54	3.33	1.51-7.34	0.003	3.15	1.43-6.96	0.004
Child-Pugh classification
A	83	Reference	N/A	N/A	N/A	N/A	N/A
B	12	2.46	1.06-5.68	0.035	N/A	N/A	N/A
C	4	1.81	0.42-7.66	0.41	N/A	N/A	N/A
Macrovascular invasion as yes/no	31/68	1.25	0.62-2.48	0.524	N/A	N/A	N/A
Overall diameter of target (tumors in cm of ≤ 7 cm/> 7 cm)	46/53	2.09	1.02-4.28	0.042	N/A	N/A	N/A
AFP of ≤ 400 ng/mL/> 400 ng/mL	74/25	1.68	0.83-3.39	0.145	N/A	N/A	N/A
Tumor differentiation
Well differentiated	3	Reference	N/A	N/A	N/A	N/A	N/A
Moderately differentiated	71	N/A	NA1	0.922	N/A	N/A	N/A
Undifferentiated	25	N/A	NA1	0.920	N/A	N/A	N/A

¹Heart rate calculation and inclusion of the covariate in univariate analysis was not applicable due to the lack of hepatocellular carcinoma deaths in the well-differentiated group.

RFS: Recurrence-free survival; 95%CI: 95% confidence interval; AFP: Alpha-fetoprotein; DEB-TACE: Drug-eluting bead transcatheter arterial chemoembolization; HR: Hazard ratio; LT: Liver transplantation; N/A: Not applicable; OS: Overall survival; NA: Not available.