Effects of Early TACE Refractoriness on Survival in Patients with Hepatocellular Carcinoma: A Real-World Study

Figures & data

Table 1 Patients Characteristics

Variables	Before PSM			After PSM
	TACE-Non-Refractoriness (n = 158)	Early TACE-Refractoriness (n = 165)	P value	TACE-Non-Refractoriness (n = 120)	Early TACE-Refractoriness (n = 120)	P value
Age	58.6 ± 9.7	58.1 ± 11.6	0.72	58.1 ± 9.6	57.9 ± 10.0	0.86
Sex			0.61			0.85
1	139 (88.0)	142 (86.1)		104 (86.7)	102 (85)
2	19 (12.0)	23 (13.9)		16 (13.3)	18 (15)
AFP			0.88			0.89
0	106 (67.1)	112 (67.9)		85 (70.8)	83 (69.2)
1	52 (32.9)	53 (32.1)		35 (29.2)	37 (30.8)
TBIL			0.12			0.60
0	89 (56.3)	107 (64.9)		67 (55.8)	72 (60)
1	69 (43.7)	58 (35.2)		53 (44.2)	48 (40)
ALT			0.04			0.30
0	100 (63.3)	86 (52.1)		72 (60)	63 (52.5)
1	58 (36.7)	79 (47.9)		48 (40)	57 (47.5)
AST			0.01			0.44
0	92 (58.2)	70 (42.4)		67 (55.8)	60 (50)
1	66 (41.8)	95 (57.6)		53 (44.2)	60 (50)
ALB			0.89			0.85
0	18 (11.4)	18 (10.9)		16 (13.3)	14 (11.7)
1	140 (88.6)	147 (89.1)		104 (86.7)	106 (88.3)
Ascites			0.57			0.68
0	154 (97.5)	159 (96.4)		118 (98.3)	116 (96.7)
1	4 (2.5)	6 (3.6)		2 (1.7)	4 (3.3)
BCLC stage			<0.001			0.62
1	66 (41.8)	38 (23.0)		41 (34.2)	36 (30)
2	80 (50.6)	90 (54.6)		68 (56.7)	69 (57.5)
3	12 (7.6)	37 (22.4)		11 (9.2)	15 (12.5)
Child-Pugh			0.51			1.00
1	155 (98.1)	160 (96.97)		119 (99.2)	118 (98.3)
2	3 (1.9)	5 (3.0)		1 (0.8)	2 (1.7)
ECOG score			0.70			1.00
0	152 (96.2)	160 (97.0)		116 (96.7)	117 (97.5)
1	6 (3.8)	5 (3.0)		4 (3.3)	3 (2.5)
Cirrhosis			0.36			1.00
0	48 (30.4)	58 (35.1)		37 (30.8)	36 (30)
1	110 (69.6)	107 (64.9)		83 (69.2)	84 (70)
TN			0.01			0.60
0	83 (52.5)	63 (38.2)		55 (45.8)	50 (41.7)
1	75 (47.5)	102 (61.8)		65 (54.2)	70 (58.3)
TD	5.79 ± 3.5	7.28 ± 3.9	<0.001	6.2 ± 3.5	6.5 ± 3. 6	0.58
Capsule			0.46			0.64
0	120 (76.0)	131 (79.4)		96 (80)	92 (76.7)
1	38 (24.0)	34 (20.6)		24 (20)	28 (23.3)
Bilobular			0.02			0.44
0	101 (63.9)	84 (50.9)		71 (59.2)	64 (53.3)
1	57 (36.1)	81 (49.1)		49 (40.8)	56 (46.7)
HBV			0.24			0.88
0	35 (22.1)	46 (27.9)		28 (23.3)	30 (25.0)
1	123 (77.9)	119 (72.1)		92 (76.7)	90 (75.0)
TACE sessions	5.4 ± 4.6	5.0 ± 3.1	0.37	5.7 ± 4.5	5.2 ± 3.3	0.34

Notes: Data are given as mean ± standard deviation or numbers (and percentage). Boldface indicates statistical significance (p<0.05).

Abbreviations: PSM, propensity score matching; TACE, transarterial chemoembolization; AFP, α-fetoprotein; TBIL, total bilirubin; ALB, albumin; HBV, hepatitis B virus; ECOG, Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; ALT, alanine aminotransferase; AST, Aspartate aminotransferase; TD, tumor diameter; TN, tumor number.

Figure 1 Flowchart of patient inclusion and exclusion.

Abbreviations: TACE, transarterial chemoembolization; PSM, propensity score matching.

Figure 2 Kaplan-Meier survival curves of HCC patients with and without early TACE-refractoriness before and after PSM. (A) Before PSM, Median OS of patients with and without early TACE refractoriness was 21 m (95% CI: 17.3–24.7) and 39 m (95% CI: 29.2–48.8), respectively (p = 0.000). (B) After PSM, median OS of patients with and without early TACE refractoriness was 21 m (95% CI: 15.7–26.3) and 34 m (95% CI: 27.5–40.5), respectively (p = 0.002).

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; PSM, propensity score matching; OS, overall survival; CI, confidence interval.

Figure 3 Overall survival of HCC patients with and without early TACE refractoriness in different BCLC stages [(A): Stage A, 28 m, (95% CI: 22.0–34.0); 57 m, (95% CI: 51.3–62.7), p = 0.000. (B): Stage B, 20 m, (95% CI: 16.1–23.9); 36 m, (95% CI: 29.2–42.8), p = 0.002. (C): Stage C, 14 m, (95% CI: 6.1–21.9); 25 m, (95% CI: 19.3–30.7), p = 0.398].

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval.

Table 2 Patients Characteristics After PSM (TACE-Non-Refractoriness and TACE-Refractoriness*)

Variables	TACE-Non-Refractoriness (n = 33)	TACE-Refractoriness* (n = 33)	P value
Age			0.45
0	15 (45.5)	11 (33.3)
1	18 (54.5)	22 (66.7)
Sex			1.00
1	26 (78.8)	25 (75.8)
2	7 (21.2)	8 (24.2)
AFP			0.76
0	27 (81.8)	25 (75.8)
1	6 (18.2)	8 (24.2)
TBIL			0.80
0	20 (60.6)	22 (66.7)
1	13 (39.4)	11 (33.3)
ALT			1.00
0	23 (69.7)	22 (66.7)
1	10 (30.3)	11 (33.3)
AST			0.81
0	17 (51.5)	15 (45.5)
1	16 (48.5)	18 (54.5)
ALB			0.73
0	6 (18.2)	4 (12.1)
1	27 (81.8)	29 (87.9)
Ascites			1.00
0	32 (97)	32 (97)
1	1 (3)	1 (3)
BCLC stage			0.32
1	13 (39.4)	8 (24.2)
2	17 (51.5)	19 (57.6)
3	3 (9.1)	6 (18.2)
Child-Pugh			0.47
1	31 (93.9)	33 (100)
2	2 (6.1)	0 (0)
ECOG score			1.00
0	32 (97)	32 (97)
1	1 (3)	1 (3)
Cirrhosis			0.61
0	10 (30.3)	13 (39.4)
1	23 (69.7)	20 (60.6)
TN			0.80
0	15 (45.5)	13 (39.4)
1	18 (54.5)	20 (60.6)
TD	6.1 ± 3.38	7.2 ± 3.4	0.22
Capsule			0.79
0	24 (72.7)	22 (66.7)
1	9 (27.3)	11 (33.3)
Bilobular			0.44
0	23 (69.7)	19 (57.6)
1	10 (30.3)	14 (42.4)
HBV			1.00
0	10 (30.3)	11 (33.3)
1	23 (69.7)	22 (66.7)
TACE sessions	4.1 ± 2.6	6.9 ± 3.6	0.00

Notes: Data are given as mean ± standard deviation or numbers (and percentage). TACE refractoriness* means viable lesion>50% after two consecutive TACE sessions. Boldface indicates statistical significance (p<0.05).

Abbreviations: PSM, propensity score matching; TACE, transarterial chemoembolization; AFP, α-fetoprotein; TBIL, total bilirubin; ALB, albumin; HBV, hepatitis B virus; ECOG, Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; ALT, alanine aminotransferase; AST, Aspartate aminotransferase; TD, tumor diameter; TN, tumor number.

Figure 4 The median OS was 35 m (95% CI: 21.6–48.5) in the early TACE-refractory group (viable lesions > 50%) and 31 m (95% CI: 25.4–36.6) in the nonrefractory group after PSM (p = 0.611).

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; PSM, propensity score matching; CI, confidence interval.

Table 3 Predictors of Death for HCC Patients Treated by TACE

Variables	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P value	HR	95% CI	P value
Sex, (reference: male)	1.27	0.86–1.89	0.24
Age, (reference:<60y)	0.92	0.69–1.23	0.58
AFP, (reference:<400)	1.91	1.40–2.59	0.00	1.66	1.20–2.31	0.003
TBIL, (reference:<17)	1.06	0.79–1.41	0.71
ALT, (reference:<40)	1.05	0.79–1.40	0.75
AST, (reference:<40)	1.2	0.90–1.59	0.22
ALB, (reference:<35)	1.43	0.89–2.30	0.14
Ascites, (reference: no)	2.29	1.01–5.18	0.05
BCLC, (reference: A, B)	2.2	1.42–3.42	0.00	1.82	1.12–2.96	0.016
Child-Pugh, (reference: A)	0.63	0.16–2.53	0.51
ECOG, (reference: 0)	1.51	0.71–3.22	0.28
Cirrhosis, (reference: 0)	1.17	0.86–1.59	0.33
TN, (reference: <3)	0.99	0.74–1.32	0.93
TD, (reference: <3cm)	1.51	1.05–2.18	0.03	1.67	1.14–2.44	0.008
Capsule, (reference: no)	0.62	0.43–0.89	0.01	0.46	0.35–0.74	0.000
Bilobular, (reference: no)	1.45	1.09–1.94	0.01	1.45	1.08–1.95	0.015
HBV, (reference: no)	1.07	0.77–1.48	0.70
Early refractoriness, (reference: no)	1.57	1.18–2.10	0.00	1.60	1.20–2.14	0.001

Note: Boldface indicates statistical significance (p<0.05).

Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; AFP, α-fetoprotein; TBIL, total bilirubin; ALB, albumin; HBV, hepatitis B virus; ECOG, Eastern Cooperative Oncology Group; BCLC, Barcelona Clinic Liver Cancer; ALT, alanine aminotransferase; AST, Aspartate aminotransferase; TD, tumor diameter; TN, tumor number; HR, hazard ratio; CI, confidence interval.