Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients

Table 1 Patient demographics and tumor characteristics

Clinical parameter	Sorafenib	Control	P value2
No. of patients	34	68	-
Males	25	50	-
Age, yr1	48 (21-78)	57 (18-79)	0.142
Platelet count, 109/L1	121 (31-368)	156 (30-317)	0.046
Serum albumin, g/L1	38 (26-52)	36 (24-51)	0.387
Serum total bilirubin, mmol/L1	14.6 (5.1-48.3)	16.4 (7.6-51.5)	0.283
AST, IU/L1	56 (11-526)	59 (12-498)	0.525
Hemoglobin, g/L1	12.5 (6.6-18.6)	11.5 (5.9-17.3)	0.275
AFP ≥ 400, mg/L	23	45	0.882
Hepatitis B virus infection	29 (93.3%)	59 (92.0%)	0.692
ICG retention at 15 min, %1	7.7 (1.5-14.2)	7.3 (2.3-13.8)	0.482
Child–Pugh grade, A/B	27/7	54/14	-
HBV DNA, > 1/ ≤ 1 × 105 copy/mL	26/8	49/19	0.634
Prothrombin time, s1	14 (10-17)	14 (10-19)	0.224
Tumor size, cm1	6.4 (2.8-20.2)	5.9 (2.9-21.3)	0.098
Tumor number1	2 (1-8)	2 (1-10)	0.187
Hilar lymph nodes metastasis, yes/no	11/23	29/39	0.315
Liver cirrhosis, yes/no	30/4	60/8	-
ECOG performance status score, PS = 0/1	31/3	61/7	0.814
Median follow-up time, mo	26	25	-

¹Value expressed in median with range in parentheses;

²Study group compared with control group.

Table 2 Surgical outcomes

Variable	Sorafenib	Control	P value2
Type of resection			-
Minor	8	16
Major3	26	52
Intraoperative blood loss, mL1	350 (50-1600)	380 (50-1800)	0.132
Intraoperative blood transfusion, mL1	650 (0-1500)	600 (0-1600)	0.126
No. of patients without transfusion, %	31 (75.0%)	58 (81.48%)	0.139
Postoperative AST on day 3, IU/L1	226 (48-896)	327 (68-1237)	0.042
Postoperative total bilirubin on day 3, mmol/L1	42 (19-276)	39 (18-212)	0.138
Infectious morbidity	8	12	0.566
Lung infection	3	4
Abdominal collection	4	6
Infection of incisional wound	1	1
Sepsis	0	1
Noninfectious morbidity	4	9	0.853
Pleural effusion	3	5
Bile leak	1	4
Liver failure	0	0

¹Value expressed in median with range in parentheses;

²Study group compared with control group;

³Major hepatectomy was defined as resection of three or more segments.

Table 3 Type of recurrence

Type of recurrence	Sorafenib	Control	P value1
Hepatic	8	28	0.079
Extrahepatic	5	12	0.707
Hepatic + extrahepatic	2	11	0.142
Overall hepatic recurrence	10	39	0.008
Overall extrahepatic	7	23	0.167
Total recurrence	15 (44.1%)	51 (75.0%)	0.002

¹Study group compared with control group.

Table 4 Univariate and multivariate analyses of potential risk factors of tumor recurrence

Risk factors1	Univariate analysis			Multivariate analysis
	Hazard ratio	95%CI	P value(Cox’s regression)	Hazard ratio	95%CI	P value(Cox’s regression)
Sex, male/female	1.159	1.934-1.402	0.118
Age, > 50/ ≤ 50 yr	1.003	0.961-1.012	0.751
Platelet count, > 100/ ≤ 100 × 109/L	1.258	0.939-1.626	0.095
Hemoglobin, > 10/ ≤ 10 g/L	1.119	0.867-1.411	0.089
Serum AFP, > 400/ ≤ 400 ng/mL	0.960	0.929-1.011	0.079
HBV infection, yes/no	0.931	0.593-1.449	0.769
HBV DNA, > 1/ ≤ 1 × 105 copy/mL	1.323	0.912-1.883	0.119
AST, > 42/ ≤ 42 IU/L	1.171	0.933-1.425	0.127
Serum albumin, > 38/ ≤ 38 g/L	1.264	0.961-1.665	0.095
Serum total bilirubin, > 21/ ≤ 21 mmol/L	0.965	0.923-1.010	0.075
Prothrombin time, > 12.8/ ≤ 12.8 s	1.162	0.931-1.324	0.126
ICG retention at 15 min, > 10%/ ≤ 10%	1.349	0.903-1.989	0.115
Child-Pugh grade, A/B	1.011	0.914-1.097	0.779
Tumor size, > 50/ ≤ 50 mm	0.957	0.904-1.014	0.075
HBsAg, positive/negative	1.241	0.948-1.649	0.094
HBeAg, positive/negative	1.174	0.938-1.422	0.121
Type of resection, minor/major	1.131	0.949-1.381	0.086
Tumor number, < 3/≥ 3	2.050	1.051-3.549	0.034	1.324	1.035-1.776	0.045
Macrovascular invasion, yes/no	1.242	1.061-1.501	0.035
Hilar lymph nodes metastasis, yes/no	1.058	1.006-1.111	0.043
Sorafenib, yes/no	1.012	1.003-1.099	0.034a	1.353	1.012-1.763	0.039

¹The number of patients forin each risk factor analyzed = 102.

Table 5 Comparison of outcomes of patients with Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma treated by various interventions

Study	Year	Number of patients	Interventions	Median OS, mo	1-, 3-, 5-yr
					DFS, %	OS, %
Llovet et al[9]	2008	299	Sorafenib	10.7	-	44/-/-1
		303	Placebo	7.9	-	33/-/-
Cheng et al[22]	2009	150	Sorafenib	6.5	-	53.3/-/-1
		76	Placebo	4.2	-	36.7/-/-1
Wörns et al[23]	2009	22	Sorafenib	3.3	-	-
Yau et al[24]	2009	51	Sorafenib	5.0	-	-
Ozenne et al[25]	2010	50	Sorafenib	5.5	-	-
Baek et al[26]	2011	201	Sorafenib	5.3	-	-
Iavarone et al[27]	2011	296	Sorafenib	10.51
Santini et al[28]	2012	93	Sorafenib	12.01
Zhao et al[29]	2013	222	Sorafenib and TACE	12.01
Minagawa et al[30]	2001	18	Liver resection			82/42/42
Chirica et al[31]	2008	20	Liver resection	32.0	40/20/171	73/56/451
Ishizawa et al[32]	2008	98	Liver resection		-/37/25	-/71/56
Wang et al[33]	2008	14	Liver resection	13.0		57/29/29
Torzilli et al[34]	2008	28	Liver resection		66/17/-	80/74/-
Yang et al[35]	2012	511	Liver resection	27.8	48/30/24	70/41/31
Torzilli et al[10]	2013	297	Liver resection		46/28/18	76/49/38
This study	2014	68	Liver resection	18.0	42/26/-	69/34/-
		34	Liver resection and Sorafenib	25.0	63/37/-	88/53/-

¹Including patients with BCLC-stage B. DFS: Disease-free survival; OS: Overall survival; TACE: Transarterial chemoembolization.