Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein

Table 1 Characteristics of hepatocellular carcinoma patient with portal vein tumor thrombus invading the main portal vein trunk and inferior vena cava n (%)

	Group 1 (n = 307)			Group 2(n = 54)	Group 3(n = 15)	Group 4(n = 42)	P value
	TACE(n = 274)	TACE-sorafenib(n = 33)	P value
Baseline characteristic
Age, mean ± SD	48.62 ± 12.09	49.51 ± 11.23	0.764	47.40 ± 17.48	49.78 ± 21.26	51.49 ± 23.23	0.668
Sex (M)	233 (85.0)	26 (78.8)	0.350	46 (85.2)	12 (80.0)	36 (85.7)	0.960
Clinical characteristic
Positive for HBsAg	224 (81.8)	29 (87.9)	0.505	46 (85.2)	14 (93.3)	36 (85.7)	0.665
Positive for anti-HCV	16 (5.8)	0 (0.0)	0.234	1 (1.9)	0 (0.0)	1 (2.3)	0.755
PLT (109/L)	198.25 ± 88.17	205.94 ± 102.04	0.146	246.37 ± 71.13	211.74 ± 101.21	297.10 ± 148.07	0.654
TBil (μmol/L)	19.1 (13.08-30.10)	16.70 (11.80-23.00)	0.347	21.1 (11.46-32.37)	17.23 (10.79-35.69)	25.1 (10.78-41.76)	0.065
ALB (g/L)	37.29 ± 5.14	37.74 ± 4.64	0.981	39.31 ± 7.81	36.73 ± 4.27	32.13 ± 8.23	0.851
ALT (U/L)	54.00 (35.00-79.00)	52.00 (35.00-99.00)	0.813	52.00 (32.00-77.00)	56.00 (31.00-72.00)	58.00 (31.00-81.00)	0.135
AST (U/L)	79.00 (49.00-144.00)	80.00 (50.00-157.50)	0.843	65.00 (28.00-101.00)	78.00 (45.00-127.00)	75.00 (21.00-167.00)	0.104
PT (s)	13.75 ± 1.52	13.84 ± 1.934	0.963	12.11 ± 1.41	13.49 ± 1.37	13.79 ± 1.54	0.060
AFP (mg/L)	873 (126-12100)	1210 (123-12100)	0.107	745 (310-12100)	691 (348-12100)	1207 (1001-12100)	0.793
Child-Pugh Score	5 (5-8)	5 (5-8)	0.914	5 (5-8)	6 (5-8)	6 (5-9)	0.255
Ascites	8 (2.9)	0 (0.0)	0.999	0 (0.0)	0 (0.0)	3 (7.1)	0.201
Pathological characteristic
Tumor size (cm)	6.78 ± 2.96	7.14 ± 3.97	0.101	7.13 ± 2.73	6.97 ± 2.37	7.95 ± 3.34	0.437
Tumor number (≥ 3), n	178 (65.0)	22 (66.7)	0.846	17 (32.4)	9 (60.0)	27 (64.2)	0.982
Cirrhosis, n	223 (81.0)	27 (81.8)	0.952	46 (85.2)	11 (73.3)	36 (88.1)	0.697
Portal vein hypertension, n	76 (27.7)	8 (24.2)	0.671	12 (22.2)	3 (20.0)	14 (33.3)	0.609
Main portal vein trunk, n	211 (77.0)	21 (63.6)	0.091	44 (81.5)	6 (77.0)	17 (77.0)	< 0.001
Inferior vena cava, n	63 (23.0)	12 (36.4)		10 (18.5)	9 (77.0)	25 (77.0)

PVTT: Portal vein tumor thrombus; SD: Standard deviation; HBsAg: Hepatitis B surface antigen; anti-HCV: Hepatitis C virus antibody; PLT: Platelet count; TBil: Total bilirubin; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; PT: Prothrombin time; AFP: Alpha-fetoprotein; Group 1: TACE; Group 2: Surgery + postoperative TACE; Group 3: Monotherapy of sorafenib; Group 4: Palliative therapy.

Table 2 Survival period and survival rate in different groups

	Mean overall survival (mo)	3-mo survival rate	6-mo survival rate	12-mo survival rate	24-mo survival rate
TACE administration	10.39	94.1%	85.9%	51.5%	0.0%
TACE subgroup	10.22	93.8%	86.7%	43.9%	0.0%
TACE-sorafenib subgroup	10.52	95.3%	83.3%	53.8%	0.0%
Liver resection + TACE	4.13	60.3%	22.2%	0.0%	0.0%
Targeted therapy of sorafenib	3.54	50.9%	29.5%	0.0%	0.0%
Palliate treatment	2.82	55.0%	0.0%	0.0%	0.0%

TACE: Transcatheter arterial chemoembolization.

Table 3 Complications and adverse events in different therapy groups n (%)

Complication	Group 1 (n = 307)			Group 2(n = 54)	Group 3(n = 15)	P value
	TACE(n = 274)	TACE-sorafenib (n = 33)	P value
Nausea, vomiting	49 (17.9)	19 (57.6)	< 0.001	12 (22.2)	12 (80.0)	< 0.001
Fever	62 (22.6)	8 (24.2)	0.835	11 (20.4)	0 (0.0)	< 0.001
Pain	119 (43.4)	7 (21.2)	0.047	24 (44.4)	0 (0.0)	< 0.001
Alopecia	3 (1.1)	11 (33.3)	< 0.001	3 (5.6)	6 (40.0)	< 0.001
Bleeding of tumor rupture	0 (0.0)	2 (6.0)	< 0.001	0 (0.0)	0 (0.0)	< 0.001
Liver failure	1 (0.4)	25 (75.8)	< 0.001	5 (9.3)	4 (26.7)	< 0.001
Bile leakage	0 (0.0)	0 (0.0)	0.999	4 (7.4)	0 (0.0)	< 0.001
Bleeding of esophageal venous plexus	0 (0.0)	0 (0.0)	0.999	2 (3.7)	0 (0.0)	< 0.001
Gastrointestinal hemorrhage	0 (0.0)	1 (3.0)	0.004	1 (1.9)	1 (6.7)	< 0.001
Heart failure	0 (0.0)	0 (0.0)	0.999	1 (1.9)	0 (0.0)	< 0.001
Infection	1 (0.4)	0 (0.0)	0.999	1 (1.9)	0 (0.0)	< 0.001
Ectopic embolism syndrome	1 (0.4)	0 (0.0)	0.999	0 (0.0)	0 (0.0)	< 0.001
Refractory ascites	0 (0.0)	0 (0.0)	0.999	3 (5.6)	0 (0.0)	< 0.001
Pulmonary complication	1 (0.4)	1 (3.0)	0.072	7 (13.0)	0 (0.0)	< 0.001
Therapy-related death	0 (0.0)	0 (0.0)	0.999	51 (9.3)	0 (0.0)	< 0.001

¹Three patients died of postoperative liver failure, 1 patient was observed in right atrium and died of heart failure, and 1 patient died of badly infection. Group 1: TACE; Group 2: Surgery + postoperative TACE; Group 3: Monotherapy of sorafenib; Group 4: Palliative therapy.

Table 4 Adverse events related to sorafenib administration n (%)

Adverse event	Mono-therapy of sorafenib			TACE combined with sorafenib
	All events	Grade 1-2 events	Grade 3-4 events	All events	Grade 1-2 events	Grade 3-4 events
Overall incidence	14 (93.3)	12 (80.0)	2 (13.3)	30 (90.9)	26 (78.8)	4 (12.1)
Alopecia	6 (40.0)	6 (40.0)	0 (0.0)	11 (33.3)	11 (33.3)	0 (0.0)
Anorexia	4 (26.7)	4 (26.7)	0 (0.0)	18 (54.5)	18 (54.5)	0 (0.0)
Diarrhea	13 (86.7)	12 (80.0)	1 (6.7)	27 (81.8)	26 (78.8)	1 (3.0)
Epistaxis	1 (6.7)	1 (6.7)	0 (0.0)	2 (6.0)	2 (6.0)	0 (0.0)
Fatigue	12 (80.0)	12 (80.0)	0 (0.0)	22 (66.7)	21 (63.6)	1 (3.0)
Gastrointestinal hemorrhage	1 (6.7)	1 (6.7)	0 (0.0)	1 (3.0)	1 (3.0)	0 (0.0)
Hand-foot skin reactions	11 (73.3)	10 (66.7)	0 (0.0)	12 (36.3)	11 (33.3)	1 (3.0)
Liver dysfunction	4 (26.7)	4 (26.7)	1 (6.7)	25 (75.8)	23 (69.7)	2 (6.0)
Nausea	12 (80.0)	12 (80.0)	0 (0.0)	19 (57.6)	19 (57.6)	0 (0.0)

TACE: Transcatheter arterial chemoembolization.

Table 5 Factors affecting overall survival using Cox’s proportional hazard model

Factor	Univariate analysis				Multivariate analysis
	Patients, n	Mean OS (mo)	95%CI	P value	HR	95%CI	P value
Positive for HBsAg
Yes	349	9.05	8.33-9.76	0.035	1.09	0.56-2.14	0.798
No	69	10.58	9.92-11.23
Positive for anti-HCV
Yes	19	6.00	2.49-9.51	0.026	1.45	0.44-3.88	0.454
No	399	9.42	8.90-9.94
AFP (mg/L)
> 400	134	7.99	6.94-9.05	< 0.001	1.84	1.09-3.11	0.023
≤ 400	284	9.96	9.42-10.49
Child-Pugh Stage
Stage A	262	9.88	9.34-10.42	< 0.001	1.99	1.20-3.30	0.008
Stage B	156	8.28	7.21-9.37
Tumor size (cm)
> 5	301	8.48	7.79-9.18	< 0.001	3.31	1.57-6.98	0.002
≤ 5	117	10.82	10.20-11.45
Tumor number
> 3	147	8.62	7.92-9.32	< 0.001	2.10	1.22-3.63	0.007
≤ 3	271	10.55	9.89-11.20
Cirrhosis
Yes	343	8.85	8.23-9.46	0.007	2.10	1.02-4.32	0.044
No	75	10.82	10.06-11.59
Portal hypertension
Yes	113	7.00	6.03-7.98	< 0.001	1.65	1.02-2.65	0.041
No	345	10.14	9.62-10.65
Tumor thrombus location
Main portal vein trunk	299	10.40	9.89-10.91	< 0.001	4.51	2.66-7.65	< 0.001
Inferior vena cava	119	4.83	4.26-5.41

PVTT: Portal vein tumor thrombus; HBsAg: Hepatitis B surface antigen; anti-HCV: Hepatitis C virus antibody; PLT: Platelet count; TBil: Total bilirubin; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; PT: Prothrombin time; AFP: Alpha-fetoprotein.