Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis

Figures & data

Table 1 The Baseline Characteristics of All HCC Patients with MVI Among Different Type of Treatments Before and After PSM

Variable	Before PSM				After PSM
	HAIC	TACE	Control	P	a-HAIC	a-TACE	Control	P
n	157	116	276		86	77	163
Gender (%)				0.167				0.536
Male	136 (86.6)	109 (94.0)	242 (87.7)		75 (87.2)	71 (92.2)	143 (87.7)
Female	21 (13.4)	7 (6.0)	34 (12.3)		11 (12.8)	6 (7.8)	20 (12.3)
Age (%)				0.016				0.077
≤65	141 (89.8)	112 (96.6)	243 (88.0)		76 (88.4)	74 (96.1)	142 (87.1)
>65	16 (10.2)	4 (3.4)	33 (12.0)		10 (11.6)	3 (3.9)	21 (12.9)
HBsAg (%)				0.835				0.537
Negative	20 (12.7)	14 (12.1)	39 (14.1)		12 (14.0)	9 (11.7)	28 (17.2)
Positive	137 (87.3)	102 (87.9)	237 (85.9)		74 (86.0)	68 (88.3)	135 (82.8)
ALT (%)				0.138				1.000
≤40	101 (64.3)	61 (52.6)	159 (57.6)		50 (58.1)	45 (58.4)	96 (58.9)
>40	56 (35.7)	55 (47.4)	117 (42.4)		36 (41.9)	32 (41.6)	67 (41.1)
Tbil (%)				0.229				0.339
≤20.5	142 (90.4)	102 (87.9)	234 (84.8)		78 (90.7)	68 (88.3)	137 (84.0)
>20.5	15 (9.6)	14 (12.1)	42 (15.2)		8 (9.3)	9 (11.7)	26 (16.0)
ALBI (%)				0.032				0.309
I	127 (80.9)	81 (69.8)	224 (81.2)		74 (86.0)	59 (76.6)	133 (81.6)
II	30 (19.1)	35 (30.2)	52 (18.8)		12 (14.0)	18 (23.4)	30 (18.4)
AFP (%)				0.354				0.354
≤400	88 (56.1)	57 (49.1)	157 (56.9)		52 (60.5)	38 (49.4)	92 (56.4)
>400	69 (43.9)	59 (50.9)	119 (43.1)		34 (39.5)	39 (50.6)	71 (43.6)
Tumor diameter (cm)				0.016				1.000
<10	132 (84.1)	83 (71.6)	225 (81.5)		76 (88.4)	62 (80.5)	136 (83.4)
≥10	25 (15.9)	33 (28.4)	51 (18.5)		10 (11.6)	15 (19.5)	27 (16.6)
Cirrhosis (%)				0.059				0.703
Absent	78 (49.7)	72 (62.1)	112 (40.6)		40 (46.5)	41 (53.2)	81 (49.7)
Present	79 (50.3)	44 (37.9)	164 (59.4)		46 (53.5)	36 (46.8)	82 (50.3)
Resection margin (cm)				<0.001				0.626
<1	25 (15.9)	49 (42.2)	127 (46.0)		22 (25.6)	25 (32.5)	47 (28.8)
≥1	132 (84.1)	67 (57.8)	149 (54.0)		64 (74.4)	52 (67.5)	116 (71.2)
Child-Pugh grade				0.513				0.498
A	155 (98.7)	116 (100.0)	272 (98.6)		85 (98.8)	76 (100.0)	163 (100.0)
B	2 (1.3)	0 (0.0)	4 (1.4)		1 (1.2)	0 (0.0)	0 (0.0)
Time to recurrence (months)
≤24	63 (40.1)	65 (56.0)	165 (59.8)	<0.001	31 (36.0)	39 (50.6)	99 (60.7)	0.001
>24	6 (3.8)	21 (18.1)	15 (5.4)	<0.001	4 (4.7)	16 (20.8)	9 (5.5)	<0.001
Patterns of tumor recurrence
Intrahepatic	55 (35.0)	75 (64.7)	148 (53.6)	<0.001	28 (32.6)	45 (58.4)	89 (54.6)	0.001
Extrahepatic	28 (17.8)	23 (19.8)	61 (22.1)	0.562	17 (19.8)	14 (18.2)	38 (23.3)	0.618

Notes: Bold values indicate statistical significance (P < 0.05).

Abbreviations: HCC, hepatocellular carcinoma; PSM, propensity score matching; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization; HBsAg, hepatitis B surface antigen; ALT, alanine aminotransferase; TBIL, total serum bilirubin; ALBI, Albumin-Bilirubin; AFP, alpha-fetoprotein.

Table 2 Univariate and Multivariate Analysis for DFS and OS in HCC Patients with MVI in Adjuvant Treatment and Control Group After PSM

Cohort	Variables	DFS						OS
		Univariate	95% CI	P	Multivariate	95% CI	P	Univariate	95% CI	P	Multivariate	95% CI	P
		HR			HR			HR			HR
After PSM (n=326)	Gender (Male/Female)	0.833	0.519–1.338	0.451				1.215	0.680–2.171	0.510
	Age (>/≤ 65 years)	0.998	0.988–1.010	0.846				0.835	0.447–1.560	0.572
	HBsAg (Absent/Present)	1.249	0.820–1.900	0.300				0.943	0.561–1.584	0.824
	Tumor diameter (</≥10cm)	1.507	1.071–2.120	0.019	1.349	0.951–1.911	0.093	2.249	1.460–3.466	0.000	1.993	1.286–3.090	0.002
	Resection margin (>/≤ 1cm)	0.950	0.700–1.290	0.740				0.886	0.591–1.328	0.558
	ALBI (grade I/II)	1.615	1.155–2.260	0.005	1.695	1.194–2.406	0.003	1.655	1.050–2.609	0.030	1.368	0.862–2.170	0.184
	AFP (>/≤400 ng/mL)	1.422	1.075–1.881	0.014	1.502	1.134–1.989	0.005	1.227	0.838–1.799	0.293
	Cirrhosis (Absent/Present)	1.314	0.993–1.739	0.056				1.236	0.844–1.810	0.275
	Type of treatment
	Control
	a-TACE	0.683	0.491–0.949	0.023	0.633	0.454–0.880	0.007	1.192	0.790–1.797	0.402	1.121	0.743–1.692	0.587
	a-HAIC	0.431	0.294–0.632	0.000	0.449	0.305–0.660	0.000	0.366	0.196–0.684	0.002	0.388	0.207–0.725	0.003

Notes: Bold values indicate statistical significance (P < 0.05).

Abbreviations: HCC, hepatocellular carcinoma; PSM, propensity score matching; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization; HBsAg, hepatitis B surface antigen; ALBI, Albumin-Bilirubin; AFP, alpha-fetoprotein; DFS, disease-free survival; OS, overall survival.

Table 3 Risk Score Weight of Factors Which Were Significant in Multivariate Analysis

Variables	Score
	1	2
Tumor diameter	<10cm	≥10cm
Tumor number	Single	Multiple
ALBI	Grade I	Grade II
AFP	≤400 ng/mL	>400 ng/mL

Abbreviations: ALBI, Albumin-Bilirubin; AFP, alpha-fetoprotein.

Figure 1 Flow chart of our study.

Abbreviations: HCC, hepatocellular carcinoma; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization; MVI, microvascular invasion; PSM, propensity score matching.

Figure 2 The Kaplan-Meier survival analysis of HCC patients DFS (A) and OS (B) before PSM between a-HAIC, a-TACE and control group.

Abbreviations: DFS, disease-free survival; OS, overall survival; HCC, hepatocellular carcinoma; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization; PSM, propensity score matching.

Figure 3 The Kaplan-Meier survival analysis of HCC patients DFS (A) and OS (B) after PSM between a-HAIC, a-TACE and control group.

Abbreviations: DFS, disease-free survival; OS, overall survival; HCC, hepatocellular carcinoma; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization; PSM, propensity score matching.

Figure 4 The Kaplan-Meier survival analysis for subgroups of HCC patients. (A) The Kaplan-Meier curves of DFS between high-TTAA group and low-TTAA group after PSM. (B) The Kaplan-Meier curves of DFS in the High-TTAA group between a-HAIC, a-TACE and control group. (C) The Kaplan-Meier curves of DFS in the Low-TTAA group between a-HAIC, a-TACE and control group. (D) The Kaplan-Meier curves of OS between high-TTAA group and low-TTAA group after PSM. (E) The Kaplan-Meier curves of OS in the High-TTAA group between a-HAIC, a-TACE and control group. (F) The Kaplan-Meier curves of OS in the Low-TTAA group between a-HAIC, a-TACE and control group.

Abbreviations: DFS, disease-free survival; OS, overall survival; HCC, hepatocellular carcinoma; a-HAIC, adjuvant hepatic artery infusion chemotherapy; a-TACE, adjuvant transcatheter arterial chemoembolization.