Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

Table 1 Baseline clinical characteristics of patients

Characteristic	PTL (n = 18)	TL (n = 23)	P value
Mean age, yr ± SD	56.9 ± 8.1	58.1 ± 9.4	0.307
Gender, n ()			0.690
Male	15 (83.3)	18 (78.3)
Female	3 (16.7)	5 (21.7)
Weight, n (%)			0.794
< 60 kg	7 (38.9)	8 (34.8)
≥ 60 kg	11 (61.1)	15 (65.2)
Etiology, n (%)			0.447
HBV	16 (88.9)	22 (95.7)
Others	2 (11.1)	1 (4.3)
ECOG-PS, n (%)			0.586
0	7 (38.9)	7 (30.4)
1	11 (61.1)	16 (69.6)
Child-Pugh class, n (%)			0.209
A	18 (100)	21 (91.3)
B	0 (0)	2 (8.7)
AFP, n (%)			0.273
< 400 ng/mL	7 (38.9)	13 (56.5)
≥ 400 ng/mL	11 (61.1)	10 (43.5)
Liver cirrhosis, n (%)			0.328
Absent	0 (0)	1 (4.3)
Present	18 (100)	22 (95.7)
Extrahepatic metastasis, n (%)			0.096
Absent	14 (77.8)	12 (52.2)
Present	4 (22.2)	11 (47.8)
Size of largest nodule, n (%)			0.855
< 5 cm	2 (11.1)	3 (13.0)
≥ 5 cm	16 (88.9)	20 (87.0)
Tumor thrombus			0.373
Branch of portal vein	8 (44.4)	7 (30.4)
Main portal vein and vena cava	10 (55.6)	16 (69.6)
Tumor number			0.415
Solitary	1 (5.6)	3 (13.0)
Multiple	17 (94.4)	20 (87.0)
ALB			0.740
> 3.5 g/dL	8 (44.4)	9 (39.1)
≤ 3.5 g/dL	10 (55.6)	14 (60.9)
Treatment history
Surgery	0 (0)	0 (0)	-
RFA	2 (11.1)	3 (13.0)	0.856
TACE			0.123
1-2	15 (83.3)	14 (60.9)
> 2	3 (16.7)	9 (39.1)
ALT (U/L)	65.8 ± 80.6	45.2 ± 26.6	0.835
AST (U/L)	73.6 ± 74.5	68.5 ± 46.5	0.386
TBIL (mg/dl)	18.8 ± 7.0	17.2 ± 8.9	0.780
PT(s)	12.7 ± 1.2	13.1 ± 1.3	0.988
PTA(s)	83.2 ± 12.6	83.7 ± 11.3	0.640

PTL: PD-1 inhibitor/transcatheter arterial chemoembolization/Lenvatinib; TL: Transcatheter arterial chemoembolization/Lenvatinib; HBV: Hepatitis B Virus; ECOG-PS: Eastern Cooperative Oncology Group-performance status; AFP: Alpha fetoprotein; ALB: Albumin; TACE: Transcatheter arterial chemoembolization; ATL: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; PT: Prothrombin time; PTA: Prothrombin activity.

Table 2 Therapeutic efficacy of response and conversion therapy, n (%)

	PTL (n = 18)	TL (n = 23)	P value
CR	1 (5.6)	0 (0)
PR	2 (11.1)	3 (13.0)
SD	13 (72.2)	11 (47.8)
PD	2 (11.1)	9 (39.1)
ORR	3 (16.7)	3 (13.0)	0.752
DCR	16 (88.9)	14 (60.9)	0.046

PTL: PD-1 inhibitor/transcatheter arterial chemoembolization/Lenvatinib; TL: Transcatheter arterial chemoembolization/Lenvatinib; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate.

Table 3 Univariate and multivariate cox proportional hazard model for Median progression-free survival

Characteristic	N	Univariate			Multivariate
		mPFS	95%CI	P value	HR	95%CI	P value
Treatment				0.000	0.25	0.12-0.52	< 0.001
PTL group	18	5.4	3.61-7.25
TL group	23	2.7	1.73-3.61
Gender				0.162	-	-	0.947
Male	33	4.00	2.70-5.31
Female	8	3.37	2.44-4.30
Age				0.902	-	-	0.740
≥ 55 yr	26	3.70	3.13-4.28
< 55 yr	15	3.63	1.96-5.30
Liver cirrhosis				0.015	-	-	-
Yes	40	3.7	3.39-4.01
No	1	1.17	-
Weight				0.537	-	-	-
< 60 kg	15	3.73	3.48-3.98
≥ 60 kg	26	3.27	1.87-4.67
Etiology				0.729	-	-	-
HBV	38	3.7	3.16-4.24
Others	3	4.47	0.36-8.58
PVTT				0.389	-	-	0.704
Ⅰ-Ⅱ types	15	3.7	0.76-6.64
Ⅲ-Ⅳ types	26	3.7	2.95-4.45
TACE				0.214	-	-	-
1-2 times	29	3.83	3.18-4.48
≥ 2 times	12	3.37	2.57-4.17
ECOG-PS				0.036	2.82	1.29-6.16	0.009
< 1	14	5.43	2.55-8.31
≥ 1	27	3.27	2.69-3.85
Child-Pugh grade				0.027	0.10	0.01-1.11	0.061
A	39	3.73	3.28-4.18
B	2	1.83	-
AFP				0.177	-	-	-
< 40 0 ng/mL	20	3.63	2.94-4.32
≥ 400 ng/mL	21	4.43	2.79-6.08
Extrahepatic spread				0.233	-	-	-
Yes	40	3.7	2.82-4.58
No	1	3.7	2.54-4.86
Tumor diameter				0.959	-	-	-
< 5 cm	5	4.43	1.94-6.92
≥ 5 cm	36	3.70	3.17-4.23
Anti-viral therapy				0.714	-	-	-
Yes	38	3.7	3.01-4.40
No	3	3.7	0.82-6.58
ALB				0.840	-	-	-
> 3.5 g/dL	17	3.37	2.21-4.53
≤ 3.5 g/dL	24	3.73	3.17-4.30
Family history of HBV				0.099	-	-	-
Yes	28	4.43	3.60-5.26
No	13	2.67	1.03-4.28
PT				0.561	-	-	0.915
< 13 s	25	4.00	2.69-5.31
≥ 13 s	16	2.53	0.04-5.02
TBIL				0.964	-	-	0.392
< 1.5 mg/dL	31	3.73	2.86-4.60
≥ 1.5 mg/dL	10	2.67	1.90-3.45
ALT				0.907	-	-	-
< 40 µg/mL	22	3.73	2.11-5.35
≥ 40 µg/mL	19	3.70	3.24-4.16
AST				0.849	-	-	-
< 40 µg/mL	12	3.23	1.43-5.03
≥ 40 µg/mL	29	3.70	3.12-4.28

PTL: PD-1 inhibitor/transcatheter arterial chemoembolization/Lenvatinib; TL: Transcatheter arterial chemoembolization/Lenvatinib; PVTT: Portal vein tumor thrombus; TACE: Transcatheter arterial chemoembolization; ECOG-PS: Eastern Cooperative Oncology Group-performance status; AFP: Alpha fetoprotein; ALB: Albumin; HBV: Hepatitis B virus; PT: Prothrombin time; TBIL: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate transaminase.

Table 4 Adverse events, n (%)

Adverse events	Any grades			High grades (≥ 3)
	PTL (n = 18)	TL (n = 23)	P value	PTL (n = 18)	TL (n = 23)	P value
Asthenia	7 (38.9)	5 (21.7)	0.186	0 (0.0)	0 (0.0)	-
ALT elevation	14 (77.8)	18 (78.3)	0.665	2 (11.1)	3 (13.0)	0.851
AST elevation	13(72.2)	18 (78.3)	0.971	2 (11.1)	3 (13.0)	0.851
Hand-foot skin reaction	1 (5.6)	3 (13.0)	0.435	0 (0.0)	0 (0.0)	-
Hypertension	2 (11.1)	3 (13.0)	0.856	1 (5.6)	1 (4.3)	0.863
Hypothyroidism	2 (11.1)	0 (0.0)	0.163	0 (0.0)	0 (0.0)	-
Proteinuria	2 (11.1)	3 (13.0)	0.856	0 (0.0)	1 (4.3)	0.383
Dysphonia	0 (0.0)	1 (4.3)	0.383	0 (0.0)	0 (0.0)	-
Decreased WBC	5 (27.8)	4 (17.4)	0.438	1 (5.6)	0 (0.0)	0.264
Decreased PLT	6 (33.3)	4 (17.4)	0.249	0 (0.0)	1 (4.3)	0.383
Hypoproteinemia	4 (22.2)	3 (13.0)	0.451	0 (0.0)	0 (0.0)	-
Infection	1 (5.6)	1 (4.3)	0.863	0 (0.0)	1 (4.3)	0.383
Diarrhea	3 (16.7)	2 (8.7)	0.452	0 (0.0)	0 (0.0)	-
Hepatic encephalopathy	0 (0.0)	1 (4.3)	0.383	0 (0.0)	1 (4.3)	0.383
Myocarditis	1 (5.6)	0 (0.0)	0.264	1 (5.6)	0 (0.0)	0.264
Anorexia	3 (16.7)	4 (17.4)	0.953	0 (0.0)	0 (0.0)	-
Ascites	4 (22.2)	3 (13.0)	0.451	0 (0.0)	0 (0.0)	-
Acute kidney injury	1 (5.6)	1 (4.3)	0.863	1 (5.6)	1 (4.3)	0.863
Nausea	3 (16.7)	5 (21.7)	0.693	0 (0.0)	0 (0.0)	-
Decreased weight	2 (11.1)	4 (17.4)	0.584	0 (0.0)	0 (0.0)	-
Elevated bilirubin	1 (5.6)	1 (4.3)	0.863	1 (5.6)	0 (0.0)	0.264
Alimentary tract hemorrhage	0 (0.0)	1 (4.3)	0.383	0 (0.0)	1 (4.3)	0.383

PTL: PD-1 inhibitor/transcatheter arterial chemoembolization/Lenvatinib; TL: Transcatheter arterial chemoembolization/Lenvatinib; ALT: Alanine aminotransferase; AST: Aspartate transaminase; WBC: White blood cell; PLT: Platelet.