Combination therapy reduces transarterial chemoembolization resistance in advanced hepatocellular carcinoma

Table 1 Baseline characteristics of patients in combination group and monotherapy group before and after propensity score matching, n (%)

Characteristics	Before PSM				After PSM
	Monotherapy group (n = 532)	Combination group (n = 72)	P value	SMD	Monotherapy group (n = 72)	Combination group (n = 72)	P value	SMD
Gender	-	-	0.882	-	-	-	0.325	-
Female	59 (11.1)	7 (9.72)	-	-0.023	12 (16.7)	7 (9.72)	-	-0.011
Male	473 (88.9)	65 (90.3)	-	0.023	60 (83.3)	65 (90.3)	-	0.011
Age (year), mean ± SD	54.9 ± 10.6	56.2 ± 10.5	0.33	-	58.3 ± 11.0	56.2 ± 10.5	0.25	-
Comorbid hepatitis B	-	-	0.184	-	-	-	0.669	-
No	75 (14.1)	15 (20.8)	-	-0.084	12 (16.7)	15 (20.8)	-	-0.041
Yes	457 (85.9)	57 (79.2)	-	0.084	60 (83.3)	57 (79.2)	-	0.041
AFP (μg/L)	-	-	0.826	-	-	-	0.17	-
< 400	307 (57.7)	40 (55.6)	-	-0.011	49 (68.1)	40 (55.6)	-	-0.009
≥ 400	225 (42.3)	32 (44.4)	-	0.011	23 (31.9)	32 (44.4)	-	0.009
Primary tumor size (mm)	66.0 (37.8-100)	91.5 (57.5-122)	< 0.001	0.486	85.0 (42.5-120)	91.5 (57.5-122)	0.37	0.019
Number of tumors	-	-	0.192	-	-	-	0.577	-
Single	178 (33.5)	18 (25.0)	-	-0.045	22 (30.6)	18 (25.0)	-	-0.009
Multiple	354 (66.5)	54 (75.0)	-	0.045	50 (69.4)	54 (75.0)	-	0.009
Tumor capsule	-	-	0.13	-	-	-	0.489	-
No	163 (30.6)	29 (40.3)	-	-0.068	24 (33.3)	29 (40.3)	-	-0.018
Yes	369 (69.4)	43 (59.7)	-	0.068	48 (66.7)	43 (59.7)	-	0.018
Tumor thrombus	-	-	0.001	-	-	-	0.225	-
No	408 (76.7)	42 (58.3)	-	-0.422	50 (69.4)	42 (58.3)	-	-0.036
Yes	124 (23.3)	30 (41.7)	-	0.422	22 (30.6)	30 (41.7)	-	0.036
Bilobar distribution of tumor	-	-	0.446	-	-	-	0.867	-
No	320 (60.2)	39 (54.2)	-	-0.076	37 (51.4)	39 (54.2)	-	-0.006
Yes	212 (39.8)	33 (45.8)	-	0.076	35 (48.6)	33 (45.8)	-	0.006
Child-Pugh grade	-	-	0.098	-	-	-	0.366	-
A	488 (91.7)	71 (98.6)	-	-0.072	69 (95.8)	71 (98.6)	-	-0.014
B	44 (8.3)	1 (1.4)	-	0.072	3 (4.2)	1 (1.4)	-	0.014
ECOG-PS	-	-	0.719	-	-	-	0.918	-
0	456 (85.7)	60 (83.3)	-	-0.012	61 (84.7)	60 (83.3)	-	-0.003
1	76 (14.3)	12 (16.7)	-	0.012	11 (15.3)	12 (16.7)	-	0.003
BCLC	-	-	0.042	-	-	-	0.58	-
B	304 (57.2)	32 (44.4)	-	-0.215	34 (47.2)	32 (44.4)	-	-0.014
C	228 (42.8)	40 (53.6)	-	0.215	38 (52.8)	40 (53.6)	-	0.014

PSM: Propensity score matching; SMD: Standardized mean differences; AFP: Alpha-fetoprotein; ECOG-PS: Eastern Cooperative Oncology Group performance status; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Univariate and multivariate analysis of transarterial chemoembolization resistance

Characteristics	Univariate logistic regression analysis			Multivariate logistic regression analysis
	OR	CI	P value	OR	CI	P value
Age	0.98	0.97-1	0.128	-	-	-
Female	1.15	0.59-2.24	0.687	-	-	-
Comorbid hepatitis B	1.06	0.56-2.01	0.858	-	-	-
AFP ≥ 400 μg/L	2.07	1.34-3.19	0.001	1.92	1.42-2.95	0.06
Primary tumor size	1.01	1.01-1.02	< 0.001	1.01	1-1.02	0.001
Number of multiple tumors	1.96	1.21-3.18	0.006	-	-	-
Tumor capsule	0.18	0.11-0.29	< 0.001	0.29	0.17-0.48	0.002
Tumor thrombus	4.52	2.74-7.47	0.03	-	-	-
Bilobar distribution of tumor	2.46	1.59-3.8	< 0.001	2.13	1.3-3.48	0.003
Child-Pugh grade B	2.25	1.1-4.62	0.027	2.14	1.23-4.21	0.07
BCLC-B	2.56	0.92-7.14	0.073	-	-	-
BCLC-C	6.9	2.39-19.92	0.052	-	-	-

AFP: Alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; OR: Odds ratio; CI: Confidence interval.

Table 3 Comparison of all-cause adverse events between the combination group and monotherapy group following propensity score matching, n (%)

Variable	Combination group (n = 72)	Monotherapy group (n = 72)
Patients with an adverse event from any cause	48 (66.6)	35 (48.6)
Grade 1 or 2 event	34 (47.2)	28 (38.9)
Grade 3 event	12 (16.7)	7 (9.7)
Grade 4 event	2 (2.7)	0
Grade 5 event	0	0
Dose interruption of PD-(L)1 inhibitors	5 (6.9)	0
Dose interruption of molecular targeted therapies	7 (9.7)	0
Dose reduction of PD-(L)1 inhibitors	8 (11.1)	0
Dose reduction of molecular targeted therapies	12 (16.6)	0

PD-(L)1: Programmed cell death (ligand) 1.