Hepatocellular carcinoma treated by conventional transarterial chemoembolization in field-practice: Serum sodium predicts survival

Table 1 Baseline predictors of survival in 270 patients with hepatocellular carcinoma at time of first conventional transarterial chemoembolization n (%)

Variables	n	Patients or median ± IQR	Univariate analysis		Multivariate analysis
			HR (95%CI)	P value	HR (95%CI)	P value
Patient-related characteristics
Age (yr)	270	66 ± 13	-	NS	-	-
Male sex	270	220 (81.5)	-	NS	-	-
Diabetes	270	61 (22.6)	-	NS	-	-
Etiology
Hepatitis C Virus	270	158 (58.5)	-	NS	-	-
Hepatitis B Virus	270	50 (18.5)	0.685 (0.484-0.968)	0.032	-	NS
Alcohol	270	13 (4.8)	-	NS	-	-
Other/unknown	270	49 (18.2)	-	NS	-	-
Liver cirrhosis	270	246 (91.1)	-	NS	-	-
Child-Pugh class A	268	171 (63.8)	-	NS	-	-
MELD	270	9 ± 4	-	NS	-	-
MELD-Na	270	10 ± 3	-	NS	-	-
Ascites (radiological only)	270	61 (22.6)	-	NS	-	-
Encephalopathy	269	18 (6.7)	-	NS	-	-
Esophageal varices	270	134 (49.6)	-	NS	-	-
Segmental portal vein thrombosis (non-tumor)	270	41 (15.2)	1.708 (1.203-2.424)	0.003	1.764 (1.224-2.542)	0.001
Tumor burden
Number of nodules > 3	270	86 (31.8)	1.622 (1.232-2.136)	0.001	1.41 (1.060-1.876)	0.018
Diameter of largest nodule ≥ 5 cm	269	108 (40.2)	1.557 (1.198-2.022)	0.001	1.595 (1.217-2.091)	0.001
Bilobarity	264	132 (48.9)	-	NS	-	-
Previous therapy1	270	73 (27)	-	NS	-	-
Percutaneous Ethanol Injection	270	45 (16.7)	-	NS	-	-
Radiofrequency ablation	270	8 (3)	-	NS	-	-
Liver resection	270	24 (8.9)	-	NS	-	-
Baseline laboratory values
Alanine aminotransferase (UI/L)	270	55 ± 63.5	-	NS	-	-
Gamma-glutamyl transferase (UI/L)	269	71 ± 80	-	NS	-	-
Alkaline phosphatase (UI/L)	269	261 ± 175	1.542 (1.188-2.002)	0.001	1.326 (1.008-1.743)	0.043
Albumin (g/dL)	269	3.5 ± 0.8	-	NS	-	-
Serum sodium (mEq/L)	270	138 ± 5	1.527 (1.168-1.995)	0.002	1.648 (1.249-2.176)	0.000
International normalised ratio	270	1.13 ± 0.19	-	NS	-	-
Total bilirubin (mg/dL)	270	1.1 ± 0.6	-	NS	-	-
Creatinine (mg/dL)	270	1 ± 0.3	-	NS	-	-
Alpha-fetoprotein (ng/mL)	267	24 ± 328	1.428 (1.099-1.856)	0.008	1.346 (1.027-1.763)	0.031

¹Some patients were subjected to more than one method of treatment before chemoembolization. Univariate analysis by Kaplan-Meier method of survival function. Multivariate analysis by backward stepwise cox regression. For continuous variables, median values were used to determine the cut-off. NS: Not significant; MELD: Model for End-stage Liver Disease; MELD-Na: MELD-sodium.

Table 2 Survival according to five staging systems in 270 hepatocellular carcinoma patients treated with conventional transarterial chemoembolization n (%)

Staging system		Median survival (95%CI)-mo	P value
Okuda			NS
I	161 (59.6)	27.00 (23.02-30.98)
II	103 (38.1)	21.00 (17.94-24.06)
III	6 (2.2)	16.00 (5.20-26.80)
CLIP			0.001
0	45 (16.7)	32.00 (23.18-40.82)
1	90 (33.3)	30.00 (21.02-38.98)
2	70 (25.9)	26.00 (24.23-27.77)
3	46 (17)	15.00 (10.57-19.43)
4	19 (17)	13.00 (5.89-20.11)
BCLC			0.013
A	87 (32.2)	30.00 (24.07-35.93)
B	153 (56.7)	22.00 (17.11-24.89)
C1	30 (11.1)	19.00 (6.92-31.08)
Tokyo			0.011
0	3 (1.1)	26.00 (-)
1	24 (8.9)	29.00 (9.65-48.35)
2	44 (16.3)	30.00 (15.88-44.12)
3	52 (19.3)	32.00 (27.45-36.55)
4	147 (54.4)	20.00 (17.12-22.88)
JIS			0.003
0	3 (1.1)	26.00 (-)
1	104 (38.5)	29.00 (22.83-35.17)
2	121 (44.8)	25.00 (19.38-30.62)
3	42 (15.6)	17.00 (13.46-20.54)

¹Included 25 patients with extrahepatic metastases and Child A status and 5 patients with a performance status of 1 or 2 and Child B8-9; the decision to perform transarterial chemoembolization in these patients was made on an individual basis in an era when sorafenib was not available. For each score, survival curves calculated by the Kaplan-Meier method were compared using the log rank test. A dash (-) indicates that the CI could not be calculated if the number of patients within each prognostic score was ≤ 5. NS: Not significant; CLIP: Cancer of the Liver Italian Program; BCLC: Barcelona Clinic Liver Cancer; JIS: Japanese Integrated System.

Table 3 Comparisons between receiver operating characteristic curves n (%)

Staging system	AUROC 1 yr	AUROC 2 yr
	(95%CI) [P value]	(95%CI) (P value)
OKUDA	0.492 (0.410-0.574) [0.849]	0.547 (0.478-0.615) [0.185]
CLIP	0.632 (0.548-0.716) [0.002]1	0.603 (0.536-0.670) [0.003]
BCLC	0.600 (0.524-0.676) [0.018]	0.571 (0.502-0.639) [0.045]
TOKYO	0.541 (0.457-0.626) [0.324]	0.582 (0.514-0.650) [0.020]
JIS	0.658 (0.582-0.734) [< 0.001]2	0.576 (0.508-0.644) [0.031]

Significant differences between curves:

¹CLIP vs OKUDA;

²JIS vs OKUDA. AUROC: Area under the curve; CLIP: Cancer of the Liver Italian Program; BCLC: Barcelona Clinic Liver Cancer; JIS: Japanese Integrated System.