Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

Table 1 Summary of patient demographics and baseline disease characteristics, n (%)

Variable	TACE/HAIC + S-1, n = 55	TACE/HAIC, n = 60	P value
Age in yr			0.210
mean ± SD (range)	56.3 ± 10.9 (34-81)	59.1 ± 12.7 (22-82)
Sex			0.709
Male	49 (89.1)	51 (85.0)
Female	6 (10.9)	9 (15.0)
Liver disease etiology			0.237
HBV	47 (85.5)	45 (75.0)
HCV	4 (7.3)	6 (10.0)
HBV and HCV	1 (1.8)	0
Unknown	3 (5.5)	9 (15.0)
Performance status			0.756
0	40 (72.7)	41 (68.3)
1	15 (27.3)	19 (31.7)
Child-Pugh stage			0.642
A	47 (85.5)	55 (91.7)
B	8 (14.5)	5 (8.3)
Tumor maximal size in cm			0.530
mean ± SD (range)	9.7 ± 4.7 (2.2-25.3)	10.2 ± 4.2 (2.5-21.0)
Number of tumors			0.683
1	16 (29.1)	19 (31.7)
≥ 2	34 (61.8)	38 (63.3)
Infiltrative	5 (9.1)	3 (5.0)
Portal vein invasion			0.649
No invasion	21 (38.2)	18 (30.0)
Stage I-II	24 (43.6)	30 (50.0)
Stage III-IV	10 (18.2)	12 (20.0)
Extrahepatic metastasis			0.274
Yes	41 (74.5)	38 (63.3)
No	14 (25.5)	22 (36.7)
Targeted treatment			0.846
Yes	9 (16.4)	8 (13.3)
No	46 (83.6)	52 (86.7)
AFP in ng/mL			0.579
Median (range)	4833 (0.9-1974770)	5561 (0.6-1207090)

AFP: Alpha-fetoprotein; HAIC: Hepatic arterial infusion chemotherapy; SD: Standard deviation; HBV: Hepatitis B virus; HCV: Hepatitis C virus; TACE: Transarterial chemoembolization.

Table 2 Response rates according to modified Response Evaluation Criteria in Solid Tumors criteria, n (%)

Response	Treatment group			P value
	Overall cohort	TACE/HAIC + S-1, n = 55	TACE/HAIC, n = 60
CR	8	4 (7.3)	4 (6.7)	1.000
PR	20	13 (23.6)	7 (11.7)	0.148
SD	46	23 (41.8)	23 (38.3)	0.849
PD	41	15 (27.3)	26 (43.3)	0.109
ORR	28	17 (30.9)	11 (18.3)	0.176
DCR	74	40 (72.7)	34 (56.7)	0.109

CR: Complete response; DCR: Disease control rate; HAIC: Hepatic arterial infusion chemotherapy; ORR: Objective response rate; PD: Progressive disease; PR: Partial response; SD: Stable disease; TACE: Transarterial chemoembolization.

Table 3 Univariable and multivariable Cox regression analyses for progression-free survival

Factor	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age in yr	0.99 (0.97-1.01)	0.215	-	-
Sex as female/male	0.73 (0.42-1.29)	0.283	-	-
Tumor size in cm	1.04 (1.00-1.09)	0.0401	1.04 (0.99-1.08)	0.098
Number of tumors
1	-	0.0041	-	0.0281
≥ 2	0.28 (0.12-0.62)	0.0021	0.36 (0.15-0.85)	0.0191
Infiltrative	0.48 (0.23-1.01)	0.052	0.60 (0.28-1.30)	0.193
Portal vein invasion
No invasion	-	0.566	-	-
Stage I-II	0.75 (0.43-1.30)	0.303	-	-
Stage III-IV	0.89 (0.54-1.47)	0.645	-	-
Extrahepatic metastasis	1.25 (0.83-1.89)	0.285	-	-
Child-Pugh stage, A/B	1.13 (0.62-2.06)	0.702	-	-
Performance status, 0/1	1.10 (0.73-1.66)	0.651	-	-
AFP in ng/mL	1.00 (1.00-1.00)	0.050	1.00 (1.00-1.00)	0.212
Albumin in g/L	0.97 (0.93-1.02)	0.246	-	-
Total bilirubin in mg/mL	1.02 (1.00-1.04)	0.088	1.00 (1.00-1.02)	0.960
GGT	1.00 (1.00-1.00)	0.0031	1.00 (1.00-1.00)	0.0321
ALT	1.00 (1.00-1.01)	0.114	-	-
AST	1.00 (1.00-1.01)	0.0081	1.00 (1.00-1.01)	0.149
Targeted treatment, yes/no	0.86 (0.50-1.49)	0.589	-	-
S-1 treatment, yes/no	0.90 (0.61-1.32)	0.585	-	-

¹The P value is < 0.05. CI: Confidence interval; AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; HR: Hazard ratio.

Table 4 Univariable and multivariable Cox regression analyses for overall survival

Factor	Univariable analysis		Multivariable analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Age in yr	1.00 (0.98-1.02)	0.911	-	-
Sex as female/male	0.83 (0.45-1.53)	0.559	-	-
Tumor size in cm	1.01 (0.96-1.05)	0.722	-	-
Number of tumors
1	-	< 0.0011	-	0.0122
≥ 2	0.18 (0.08-0.41)	< 0.0011	0.27 (0.11-0.68)	0.0052
Infiltrative	0.33 (0.15-0.71)	0.0042	0.47 (0.21-1.05)	0.067
Portal vein invasion
No invasion	-	0.648	-	-
Stage I-II	0.83 (0.46-1.50)	0.533	-	-
Stage III-IV	1.02 (0.58-1.78)	0.946	-	-
Extrahepatic metastasis	1.37 (0.88-2.14)	0.168	-	-
Child-Pugh stage, A/B	1.39 (0.74-2.62)	0.305	-	-
Performance status, 0/1	1.14 (0.74-1.76)	0.560	-	-
AFP in ng/mL	1.00 (1.00-1.00)	0.0162	1.00 (1.00-1.00)	0.192
Albumin in g/L	0.97 (0.92-1.02)	0.188	-	-
Total bilirubin in mg/mL	1.03 (1.00-1.05)	0.0192	1.01 (0.98-1.03)	0.505
GGT	1.00 (1.00-1.00)	< 0.0011	1.00 (1.00-1.00)	0.060
ALT	1.00 (1.00-1.01)	0.625	-	-
AST	1.00 (1.00-1.01)	0.127	-	-
Target treatment, yes/no	0.65 (0.35-1.19)	0.163	-	-
S-1 treatment, yes/no	1.00 (0.67-1.50)	0.985	-	-
Tumor response
CR	-	< 0.0011	-	< 0.0011
PR	0.02 (0.00-0.07)	< 0.0011	0.02 (0.00-0.09)	< 0.0011
SD	0.11 (0.06-0.21)	< 0.0011	0.11 (0.06-0.22)	< 0.0011
PD	0.20 (0.12-0.32)	< 0.0011	0.20 (0.12-0.32)	< 0.0011

¹The P value is < 0.001.

²The P value is < 0.05. CI: Confidence interval; AFP: Alpha-fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CR: Complete response; GGT: Gamma-glutamyl transferase; HR: Hazard ratio; PD: Progressive disease; PR: Partial response; SD: Stable disease.

Table 5 Observed adverse events according to common terminology criteria for adverse events grading, n (%)

Adverse event	TACE/HAIC + S-1, n = 55	TACE/HAIC, n = 60	P value
Liver injury			0.243
Grades 1-2	28 (50.9)	23 (38.3)
Grades 3-4	27 (49.1)	37 (61.7)
Vomiting			0.478
Grades 1-2	23 (41.8)	29 (48.3)
Grades 3-4	1 (1.8)	0 (0)
Abdominal pain			0.820
Grades 1-2	37 (67.3)	37 (61.7)
Grades 3-4	10 (18.2)	13 (21.7)
Fever			0.277
Grades 1-2	45 (81.8)	44 (73.3)
Grades 3-4	0 (0)	0 (0)
Leukopenia			0.465
Grades 1	2 (3.6)	4 (6.7)
Grades 2-4	0 (0)	0 (0)
Thrombocytopenia			0.793
Grade 1	9 (16.4)	11 (18.3)
Grade 2	7 (12.7)	7 (11.7)
Grade 3	0 (0)	1 (1.7)
Grade 4	0 (0)	0 (0)
Anemia			0.220
Grade 1	7 (12.7)	15 (25.0)
Grade 2	2 (3.6)	5 (8.3)
Grade 3	1 (1.8)	1 (1.7)
Grade 4	0 (0)	0 (0)

HAIC: Hepatic arterial infusion chemotherapy; TACE: Transarterial chemoembolization.