Efficacy and Safety of Conversion Surgery for Advanced Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy

Figures & data

Table 1 Baseline Characteristics of the Enrolled Patients

Variables	N (%)	Variables	N (%)
Sex		BCLC stage
Male	153 (89.0)	A/B	52 (30.2%)
Female	19 (11.0)	C	120 (69.8%)
Age, years		Child-Pugh class
≤50	88 (51.2)	A	158 (91.9)
>50	84 (48.8)	B	14 (8.1)
ECOG		ALBI grade
0	35 (20.3)	1	122 (70.9)
1–2	137 (79.7)	2	50 (29.1)
HBsAg		AFP, ng/mL
Positive	153 (89.0)	≤400	70 (40.7)
Negative	19 (11.0)	>400	102 (59.3)
Tumor size, cm		Albumin, g/l
≤10	133 (77.3)	≤40	48 (27.9)
>10	39 (22.7)	>40	124 (72.1)
Tumor number		Total bilirubin, μmol/l
≤3	33 (19.2)	≤20	128 (74.4)
>3	139 (80.8)	>20	44 (25.6)
PVTT		ALT, U/l
Absent	76 (44.2)	≤50	110 (64.0)
Present	96 (55.8)	>50	62 (36.0)
HVTT		AST, U/l
Absent	126 (73.3)	≤60	91 (52.9)
Present	46 (26.7)	>60	81 (47.1)
Metastasis
Absent	146 (84.9)
Present	26 (15.1)

Abbreviations: PVTT, portal vein tumor thrombosis; HVTT, hepatic vein tumor thrombosis; BCLC stage, Barcelona Clinic Liver Cancer stage; ALBI grade, albumin-bilirubin grade; AFP, alpha-fetoprotein level; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Figure 1 Flowchart of the establishment of the experimental group and the control group for comparison, which shows the patient selection of this study.

Figure 2 Kaplan-Meier plots of progression-free survival (A) and overall survival (B) in the imaging remission group and nonremission group.

Table 2 Univariate and Multivariate Analysis of Progression-Free Survival of the Enrolled Patients

Variables	Univariate Analysis	Multivariate Analysis
	P-value	HR (95% CI)	P-value
Group (HAIC/conversion surgery)	<0.001	1.55 (1.01−2.36)	0.043
Gender (male/female)	0.430
Age, year (≤50/>50)	0.285
ECOG (0/1–2)	<0.001	0.27 (0.11−0.67)	0.005
BCLC stage (A/B&C)	<0.001	0.63 (0.31−1.28)	0.205
Child-Pugh class (A/B)	0.064	3.13 (1.33−7.37)	0.009
HBsAg (negative/positive)	0.308
AFP, ng/mL (≤400/>400)	0.060	0.86 (0.59−1.26)	0.435
Tumor size, cm (≤10/>10)	<0.001	0.32 (0.19−0.52)	<0.001
Tumor number (≤3/>3)	0.273
PVTT (absent/present)	<0.001	0.74 (0.49−1.13)	0.163
HVTT (absent/present)	0.143
Extrahepatic metastasis (absent/present)	<0.001	0.59 (0.36−0.95)	0.031

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; AFP, alpha-fetoprotein level; HVTT, hepatic vein tumor thrombosis; PVTT, portal vein tumor thrombosis.

Table 3 Univariate and Multivariate Analysis of Overall Survival of the Enrolled Patients

Variables	Univariate Analysis	Multivariate Analysis
	P-value	HR (95% CI)	P-value
Group (HAIC/conversion surgery)	<0.001	4.07 (2.53−6.55)	<0.001
Gender (male/female)	0.221
Age, year (≤50/>50)	0.513
ECOG (0/1-2)	0.002	0.89 (0.60−1.32)	0.563
BCLC stage (A/B&C)	<0.001	0.95 (0.45−1.99)	0.887
Child-Pugh class (A/B)	0.019
HBsAg (negative/positive)	0.023
AFP, ng/mL (≤400/>400)	0.131
Tumor size, cm (≤10/>10)	<0.001	0.58 (0.36−0.91)	0.019
Tumor number (≤3/>3)	0.316
PVTT (absent/present)	<0.001	0.47 (0.31−0.70)	<0.001
HVTT (absent/present)	0.271
Extrahepatic metastasis (absent/present)	<0.001	0.73 (0.45−1.18)	0.200

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; AFP, alpha-fetoprotein level; HVTT, hepatic vein tumor thrombosis; PVTT, portal vein tumor thrombosis.

Table 4 Analysis of Conversion Surgery Rate of the Enrolled Patients

Variables	N	Case	Rate	P-value
Patients	172	51	0.297	–
Gender
Male	153	40	0.261	0.004
Female	19	11	0.579
Age, year
≤50	88	24	0.273	0.485
>50	84	27	0.321
ECOG
0	35	22	0.629	<0.001
1-2	137	29	0.212
BCLC stage
A/B	52	20	0.385	0.096
C	120	31	0.258
Child-Pugh class
A	158	44	0.278	0.152
B	14	7	0.500
HBsAg
Positive	153	47	0.307	0.384
Negative	19	4	0.211
AFP, ng/mL
≤400	70	23	0.329	0.446
>400	102	28	0.275
Tumor size, cm
≤10	133	51	0.383	<0.001
>10	39	0	0.000
Tumor number and location
Single or multiple on one side	19	18	0.947	<0.001
Diffuse	153	33	0.216
PVTT
Absent	76	23	0.303	0.876
Present	96	28	0.292
HVTT
Absent	126	41	0.325	0.170
Present	46	10	0.217
Extrahepatic metastasis
Absent	146	51	0.349	<0.001
Present	26	0	0.000

Abbreviations: BCLC stage, Barcelona Clinic Liver Cancer stage; AFP, alpha-fetoprotein level; PVTT, portal vein tumor thrombosis; HVTT, hepatic vein tumor thrombosis.

Figure 3 Kaplan-Meier plots of progression-free survival (A) and overall survival (B) in the HAIC maintenance group and conversion surgery group.

Table 5 Comparison of Treatment-Related Adverse Events Between the HAIC Maintenance Group and Conversion Surgery Group

	HAIC Maintenance (n=35)	Conversion Surgery (n=25)	P-value
Leukopenia (N, %)	11 (31.4)	12 (48.0)	0.193
Neutropenia (N, %)	21 (60.0)	18 (72.0)	0.337
Anemia (N, %)	4 (11.4)	8 (32.0)	0.050
Thrombocytopenia (N, %)	22 (62.9)	16 (64.0)	0.928
Elevated ALT (N, %)	24 (68.6)	24 (96.0)	0.009
Elevated AST (N, %)	28 (80.0)	25 (100.0)	0.017
Hyperbilirubinemia (N, %)	19 (54.3)	22 (88.0)	0.006
Hypoalbuminemia (N, %)	22 (62.9)	19 (76.0)	0.281
Elevated creatinine (N, %)	3 (8.6)	5 (20.0)	0.199

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Table 6 Comparison of Treatment-Related Adverse Events Between the Hepatectomy Group and Hepatectomy After HAIC Group

	Hepatectomy (n=213)	Hepatectomy After HAIC (n=107)	P-value
Biliary fistula	7 (3.3)	10 (9.3)	0.006
Abdominal hemorrhage	9 (4.2)	12 (11.2)	0.002
Ascites	9 (4.2)	11 (10.3)	0.003
Pneumonia	11 (5.2)	6 (5.6)	0.868
Intestinal obstruction	5 (2.3)	0 (0)	0.173

Figure 4 Kaplan-Meier plots of progression-free survival (A) and overall survival (B) in the HAIC maintenance group that met the resection criteria and the conversion surgery group.

Data Sharing Statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.