Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab with or Without Transhepatic Arterial Embolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and High Tumor Burden: A Multicenter Retrospective Study

Figures & data

Figure 1 Patient flowchart. A patient might meet several exclusion criteria, but they were excluded only once from the uppermost criteria.

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; TAE, transhepatic arterial embolization; PVTT, portal vein tumor thrombus; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab.

Table 1 Baseline Characteristics of Patients in Two Groups

Characteristic	Total (n=100)	THLP (n=50)	HLP (n=50)	P
Age, years, median (IQR)	56 (38–65)	56 (43–62)	55 (36–71)	0.456
Sex				0.356
Male	88 (88)	42 (84)	46 (92)
Female	12 (12)	8 (16)	4 (8)
Etiology				0.534
HBV	90 (90)	45 (90)	45 (90)
HCV	6 (6)	2 (4)	4 (8)
Others	4 (4)	3 (6)	1 (2)
Child-Pugh Class				0.826
A	71 (71)	36 (72)	35 (70)
B	29 (29)	14 (28)	15 (30)
ALBI grade				0.760
1	12 (12)	7 (14)	5 (10)
2	88 (88)	43 (86)	45 (90)
Performance status				0.629
0	78 (78)	40 (80)	38 (76)
1	22 (22)	10 (20)	12 (24)
AFP, ng/mL				0.391
≤400	32 (32)	14 (28)	18 (36)
>400	68 (68)	36 (72)	32 (64)
Tumor size, cm, mean±SD	14.6±2.7	14.1±2.9	14.2±2.5	0.715
Tumor number				0.799
1	19 (19)	10 (20)	9 (18)
≥2	81 (81)	40 (80)	41 (82)
PVTT				0.238
I	18 (18)	12 (24)	6 (12)
II	37 (37)	19 (38)	18 (36)
III	30 (30)	11 (22)	19 (38)
IV	15 (15)	8 (16)	7 (14)
Extrahepatic metastasis				>0.999
Absent	32 (32)	16 (32)	16 (32)
Present	68 (68)	34 (68)	34 (68)

Abbreviations: TAE, transhepatic arterial embolization; HIAC, hepatic arterial infusion chemotherapy; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab; IQR, interquartile range; HBV, hepatitis B virus; HCV, hepatitis C virus; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein; PVTT, portal vein tumor thrombus.

Table 2 Tumor Response in Two Groups

Response, n (%)	mRECIST				RECIST version 1.1
	Total (n=100)	THLP (n=50)	HLP (n=50)	P	Total (n=100)	THLP (n=50)	HLP (n=50)	P
Best overall response
Complete response	6 (6)	4 (8)	2 (4)		0 (0)	0 (0)	0 (0)
Partial response	56 (56)	32 (62)	24 (48)		50 (50)	30 (60)	20 (40)
Stable disease	20 (20)	8 (18)	12 (24)		29 (29)	13 (26)	16 (32)
Progressive disease	18 (18)	6 (12)	12 (24)		21 (21)	7 (14)	14 (28)
Objective response rate	62 (62)	36 (72)	26 (52)	0.039	50 (50)	30 (60)	20 (40)	0.046
Disease control rate	82 (82)	44 (88)	38 (76)	0.118	79 (79)	43 (86)	36 (72)	0.086

Abbreviations: HAIC, hepatic arterial infusion chemotherapy; TAE, transhepatic arterial embolization; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab.

Figure 2 Kaplan-Meier curves of (A) overall survival in all patients; (B) progression-free survival in all patients (C) overall survival in two groups; and (D) progression-free survival in two groups.

Abbreviations: HR, hazard ratio; CI, confidence interval; HAIC, hepatic arterial infusion chemotherapy; TAE, transhepatic arterial embolization; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab.

Figure 3 Kaplan-Meier curves of overall survival between two groups in patients (A) with PVTT I/II; (B) with PVTT III/IV; (C) without extrahepatic metastasis; (D) with extrahepatic metastasis; (E) with AFP ≥400 ng/mL and (F) with AFP <400 ng/mL.

Abbreviations: HR, hazard ratio; CI, confidence interval; NA, not available; HAIC, hepatic arterial infusion chemotherapy; TAE, transhepatic arterial embolization; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab; PVTT, portal vein tumor thrombus; AFP, alpha-fetoprotein.

Figure 4 Kaplan-Meier curves of progression-free survival between two groups in patients (A) with PVTT I/II; (B) with PVTT III/IV; (C) without extrahepatic metastasis; (D) with extrahepatic metastasis; (E) with AFP >400 ng/mL and (F) with AFP ≤400 ng/mL.

Abbreviations: HR, hazard ratio; CI, confidence interval; NA, not available; HAIC, hepatic arterial infusion chemotherapy; TAE, transhepatic arterial embolization; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab; PVTT, portal vein tumor thrombus; AFP, alpha-fetoprotein.

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

Variables	Overall Survival			Progression-Free Survival
	Univariate (p-value)	Multivariate (p-value)	HR (95% CI)	Univariate (p-value)	Multivariate (p-value)	HR (95% CI)
Treatment, (THLP vs HLP)	0.041	0.01	0.51 (0.31–0.85)	0.037	0.038	0.62 (0.40–0.97)
Age, (<60 vs ≥60 y)	0.381			0.379
HBV (yes vs no)	0.655			0.472
Child-Pugh (A vs B)	0.098			0.676
ALBI (1 vs 2)	0.128			0.549
Performance status (0 vs 1)	<0.001	0.190	0.62 (0.30–1.27)	0.034	0.518	0.83 (0.47–1.46)
Largest size (≤15 vs >15 cm)	0.102			0.072
Tumor number (1 vs >1)	0.465			0.875
AFP (≤400 vs >400 ng/mL)	0.048	0.061	0.57 (0.32–1.01)	0.350
PVTT (I & II vs III & IV)	<0.001	<0.001	0.25 (0.13–0.48)	<0.001	0.004	0.51 (0.32–0.81)
Extrahepatic metastasis (no vs yes)	<0.001	0.002	0.34 (0.20–0.69)	0.010	0.021	0.57 (0.35–0.92)

Abbreviations: TAE, transhepatic arterial embolization; HIAC, hepatic arterial infusion chemotherapy; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab; IQR, interquartile range; HBV, hepatitis B virus; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein; PVTT, portal vein tumor thrombus.

Table 4 Treatment-Related Adverse Events

Adverse events	Total (n=100)		THLP (n=50)		HLP (n=50)
	Any Grade	Grade 3/4	Any Grade	Grade 3/4	Any Grade	Grade 3/4
Abdominal pain	59 (59)	26 (26)	38 (76)	17 (34)	21 (42)	9 (18)
Nausea	59 (59)	29 (29)	35 (70)	18 (36)	24 (48)	11 (22)
Diarrhea	22 (22)	5 (5)	12 (24)	3 (6)	10 (20)	2 (4)
Decreased appetite	40 (40)	3 (3)	21 (42)	2 (4)	19 (38)	1 (2)
Rash	7 (7)	1 (1)	3 (6)	0 (0)	4 (8)	1 (2)
Fatigue	13 (13)	0 (0)	8 (16)	0 (0)	5 (10)	0 (0)
Albumin decreased	25 (25)	3 (3)	12 (24)	2 (4)	13 (26)	1 (2)
Bilirubin increased	19 (19)	2 (2)	10 (20)	1 (2)	9 (18)	1 (2)
Aminotransferase increased	47 (47)	6 (6)	29 (58)	5 (10)	18 (36)	1 (2)
White blood cell decreased	7 (7)	2 (2)	4 (8)	1 (2)	3 (6)	1 (2)
Platelet count decreased	8 (8)	1 (1)	3 (6)	0 (0)	5 (10)	1 (2)
Hypertension	19 (19)	5 (5)	9 (18)	2 (4)	10 (20)	3 (6)
Hand-foot syndrome	11 (11)	0 (0)	5 (10)	0 (0)	6 (12)	0 (0)
Dysphonia	3 (3)	1 (1)	1 (2)	0 (0)	2 (4)	1 (2)
Proteinuria	12 (12)	3 (3)	7 (14)	2 (4)	5 (10)	1 (2)
Gingival hemorrhage	18 (18)	5 (5)	8 (16)	2 (4)	10 (20)	3 (6)
Colitis	5 (5)	2 (2)	2 (4)	1 (2)	3 (6)	1 (2)
Hypothyroidism	14 (14)	3 (3)	6 (12)	2 (4)	8 (16)	1 (2)
Immunity-related adverse event	9 (9)	4 (4)	4 (8)	2 (4)	5 (10)	2 (4)

Abbreviations: TAE, transhepatic arterial embolization; HIAC, hepatic arterial infusion chemotherapy; THLP, TAE, HAIC, lenvatinib, and tislelizumab; HLP, HAIC, lenvatinib, and tislelizumab.