Comparable Clinical Outcomes Between Transarterial Chemoembolization or Hepatic Arterial Infusion Chemotherapy Combined with Tyrosine Kinase Inhibitors and PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma

Figures & data

Figure 1 Flow diagram of the patient characterization process.

Table 1 Baseline Characteristics

Characteristics	Levels	TTP (n=30)	HTP (n=51)	p
Age, years	Median (IQR)	49.5 (45.0 to 57.0)	49.0 (41.0 to 60.0)	0.463
Gender	Male	27 (90%)	44 (86.3%)	0.737
	Female	3 (10%)	7 (13.7%)
ECOG	0	18 (60%)	26 (51%)	0.578
	1	12 (40%)	25 (49%)
HBsAg	Negative	2 (6.7%)	7 (13.7%)	0.473
	Positive	28 (93.3%)	44 (86.3%)
HBV-DNA	≦ 10^3	14 (63.6%)	21 (42.9%)	0.173
	> 10^3	8 (36.4%)	28 (57.1%)
Liver cirrhosis	No	19 (63.3%)	33 (64.7%)	1.000
	Yes	11 (36.7%)	18 (35.3%)
AFP, ng/mL	≦ 400	12 (40%)	18 (35.3%)	0.853
	>400	18 (60%)	33 (64.7%)
DCP, ng/mL	≦ 400	10 (33.3%)	7 (14%)	0.078
	> 400	20 (66.7%)	43 (86%)
Child Pugh score	A (5 points)	23 (76.7%)	38 (74.5%)	1.000
	A (6 points)	7 (23.3%)	13 (25.5%)
BCLC stage	B	16 (53.3%)	10 (19.6%)	0.004
	C	14 (46.7%)	41 (80.4%)
Tumor size, cm	≦ 10	21 (70%)	21 (41.2%)	0.023
	> 10	9 (30%)	30 (58.8%)
Tumor number	Single	9 (30%)	10 (19.6%)	0.427
	Multiple	21 (70%)	41 (80.4%)
Tumor involvement	Unilobar	12 (40%)	26 (51%)	0.468
	Bilobar	18 (60%)	25 (49%)
Vascular invasion	Absence	20 (66.7%)	16 (31.4%)	0.004
	Presence	10 (33.3%)	35 (68.6%)
Extrahepatic metastasis	Absence	24 (80%)	40 (78.4%)	1.000
	Presence	6 (20%)	11 (21.6%)
PLT, 10E9/L	Median (IQR)	213.0 (168.0 to 287.0)	269.0 (187.5 to 368.0)	0.053
ALT, U/L	Median (IQR)	43.1 (32.2 to 67.2)	46.8 (40.0 to 63.8)	0.231
AST, U/L	Median (IQR)	48.7 (33.9 to 89.1)	73.5 (48.0 to 110.8)	0.049
Albumin, g/L	Median (IQR)	42.2 (36.6 to 44.6)	40.6 (35.9 to 43.8)	0.099
Total bilirubin, μmol/L	Median (IQR)	13.6 (9.9 to 18.1)	17.1 (11.3 to 22.5)	0.073
Intervention cycles	Median (IQR)	2.0 (2.0 to 4.0)	4.0 (2.5 to 5.0)	0.049
TKI duration, months	Median (IQR)	4.0 (1.5 to 12.8)	5.6 (2.2 to 13.3)	0.366
Anti-PD-1 cycles	Median (IQR)	4.0 (2.0 to 10.0)	6.0 (4.0 to 9.5)	0.034

Abbreviations: TTP, transarterial chemoembolization plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; HTP, hepatic infusion chemotherapy plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; ECOG, Eastern Cooperative Oncology Group performance status; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; AFP, alpha fetoprotein; DCP, des-gamma-carboxy prothrombin; BCLC, Barcelona Clinic Liver Cancer; PLT, blood platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

Figure 2 Kaplan–Meier curves of overall survival and progression-free survival. (A) Overall survival. (B) Progression-free survival. (C) Overall survival after propensity score matching. (D) Progression-free survival after propensity score matching.

Abbreviations: TTP, transarterial chemoembolization plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; HTP, hepatic infusion chemotherapy plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent.

Figure 3 Forest plot for survival outcomes.

Abbreviations: TTP, transarterial chemoembolization plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; HTP, hepatic infusion chemotherapy plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent.

Table 2 Summary of Best Response

Variable	Before PSM			After PSM
	TTP (n=30)	HTP (n=51)	p	TTP (n=24)	HTP (n=24)	p
	No. (%)	No. (%)		No. (%)	No. (%)
Overall Response
Complete response	2 (6.7)	1 (2.0)	0.552	2 (8.3)	0 (0)	0.489
Partial response	12 (40.0)	21 (41.2)	0.917	10 (41.7)	11 (45.8)	0.771
Stable disease	9 (30.0)	24 (47.1)	0.131	6 (25.0)	11 (45.8)	0.131
Progressive disease	5 (16.7)	3 (5.9)	0.139	5 (20.8)	1 (4.2)	0.188
Not assessable	2 (6.7)	2 (3.9)	0.624	1 (4.2)	1 (4.2)	1.000
Overall response rate	14 (46.7)	22 (43.1)	0.758	12 (50.0)	11 (45.8)	0.773
Disease control rate	23 (76.7)	46 (90.2)	0.116	18 (75.0)	22 (91.7)	0.121
Intrahepatic Response
Complete response	2 (6.7)	2 (3.9)	0.624	2 (8.3)	0 (0)	0.489
Partial response	12 (40.0)	22 (43.1)	0.782	10 (41.7)	13 (59.1)	0.386
Stable disease	10 (33.3)	24 (47.1)	0.227	7 (29.2)	9 (37.5)	0.540
Progressive disease	4 (13.3)	1 (2.0)	0.060	4 (16.7)	1 (4.2)	0.348
Not assessable	2 (6.7)	2 (3.9)	0.624	1 (4.2)	1 (4.2)	1.000
Overall response rate	14 (46.7)	24 (47.1)	0.973	12 (50.0)	13 (59.1)	0.536
Disease control rate	24 (80.0)	48 (94.1)	0.070	19 (79.2)	22 (91.7)	0.220

Abbreviations: TTP, transarterial chemoembolization plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; HTP, hepatic infusion chemotherapy plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; PSM, propensity score matching.

Table 3 Univariate and Multivariate Analysis of Risk Factors for Overall Survival and Progression-Free Survival

Variables	Overall Survival				Progression-Free SURVIVAL
	Univariate		Multivariate		Univariate		Multivariate
	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p	HR (95% CI)	p
Age (years), (≤/>50)	0.97 (0.55–1.71)	0.923			0.84 (0.51–1.38)	0.501
Sex, (female/male)	0.94 (0.37–2.37)	0.893			1.26 (0.62–2.54)	0.528
ECOG score (0/1)	1.71 (0.97–3.01)	0.062			1.48 (0.91–2.41)	0.112
Hepatitis B, (no/yes)	1.89 (0.68–5.26)	0.225			1.07 (0.49–2.35)	0.858
Liver cirrhosis (no/yes)	0.71 (0.38–1.30)	0.263			0.68 (0.40–1.15)	0.147
PLT (10E9/L), (≤/>100)	2.06 (0.28–14.93)	0.476			0.10 (0.03–0.37)	<0.001	0.07 (0.02–0.27)	<0.001
ALT (U/L), (≤/>50)	1.40 (0.80–2.45)	0.244			0.93 (0.56–1.52)	0.759
AST (U/L), (≤/>50)	3.66 (1.86–7.20)	<0.001	3.22 (1.56–6.66)	0.002	1.99 (1.19–3.35)	0.009	2.22 (1.22–4.03)	0.009
AFP (ng/mL), (≤/>400)	2.28 (1.22–4.28)	0.010	1.66 (0.86–3.24)	0.133	1.92 (1.14–3.25)	0.014	2.21 (1.21–4.01)	0.009
Child–Pugh score (5/6)	0.97 (0.50–1.86)	0.921			0.77 (0.43–1.37)	0.374
BCLC (B/C)	1.13 (0.61–2.08)	0.695			1.08 (0.65–1.81)	0.76
Tumor size (cm), (≤/>10)	1.55 (0.89–2.72)	0.124			1.26 (0.78–2.05)	0.347
Tumor number (1/>1)	1.51 (0.75–3.03)	0.250			1.34 (0.74–2.44)	0.329
Tumor involvement (unilobar/bilobar)	1.31 (0.74–2.30)	0.351			1.49 (0.91–2.42)	0.113
Vascular invasion (no/yes)	1.22 (0.69–2.15)	0.495			1.04 (0.64–1.69)	0.871
Extrahepatic metastasis (no/yes)	1.44 (0.75–2.77)	0.273			2.22 (1.25–3.95)	0.007	3.50 (1.81–6.77)	<0.001
Treatment (TTP/HTP)	1.23 (0.66–2.29)	0.524	0.91 (0.47–1.75)	0.774	0.70 (0.42–1.16)	0.163	0.68 (0.38–1.20)	0.184

Abbreviations: ECOG, Eastern Cooperative Oncology Group performance status; PLT, blood platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AFP, alpha fetoprotein; BCLC, Barcelona Clinic Liver Cancer; TTP, transarterial chemoembolization plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent; HTP, hepatic infusion chemotherapy plus tyrosine kinase inhibitors and anti-programmed cell-death-protein-1 agent.