Proposal of new expanded selection criteria using total tumor size and 18F-fluorodeoxyglucose - positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma: The National Cancer Center Korea criteria

Table 1 Multivariable analysis of prognostic factors for overall and disease-free survival

		Overall survival			Disease-free survival
Multivariable analysis		HR	95%CI	P	HR	95% CI	P
Variables
AFP	> 400 ng/mL	1.145	0.543-2.418	0.722	1.003	0.556-1.811	0.991
PET/CT	Positive	2.652	1.384-5.085	0.003	2.517	1.481-4.279	0.001
Tumor number	> 3	0.647	0.294-1.425	0.280	0.814	0.425-1.557	0.534
Maximum tumor size	> 5 cm	0.696	0.307-1.580	0.386	1.551	0.836-2.877	0.164
Total tumor size	> 10 cm	2.909	1.230-6.880	0.015	3.003	1.536-5.870	0.001
Differentiation1	III-IV	1.206	0.616-2.358	0.585	1.010	0.594-1.717	0.972
Microvascular invasion	Present	1.269	0.522-3.084	0.599	2.148	1.064-4.336	0.033
Capsule formation	Present	0.439	0.166-1.162	0.097	0.737	0.353- 1.542	0.418
Major vessel invasion	Present	2.017	0.829-4.905	0.122	1.712	0.850-3.449	0.132
Ductal invasion	Present	0.907	0.265-3.100	0.876	1.409	0.534-3.720	0.489
Serosal invasion	Present	1.463	0.670-3.195	0.339	1.047	0.553-1.984	0.887
Intrahepatic metastasis	Present	1.471	0.595-3.640	0.404	1.519	0.752-3.070	0.244
Dysplastic nodule	Present	0.744	0.365-1.514	0.414	0.840	0.478-1.479	0.546

¹Edmondson-Steiner Grade. CT: Computed tomography; PET: Positronemission tomography; AFP: α-fetoprotein.

Table 2 Clinicopathologic characteristics of patients according to National Cancer Center Korea criteria

Variables		Within NCCK (n = 164)	Beyond NCCK (n = 116)	P value
Sex, n (%)	Male	138 (84.1)	97 (83.6)	1
	Female	26 (15.9)	19 (16.4)
Age (yr), mean (SD)		54.2 (7)	54.7 (7.7)	0.561
MELD score, mean (SD)		14.4 (7.9)	12.5 (6.1)	0.029
C-reactive protein (mg/dL), mean (SD)		0.58 (1.11)	1.37 (2.67)	0.004
Tumor maximum SUV, mean (SD)		3.08 (0.64)	4.13 (1.79)	< 0.001
Tumor total size, n (%)	≤ 10 cm	164 (100)	56 (48.3)	< 0.001
	> 10 cm	0 (0)	60 (51.7)
AFP, n (%)	≤ 400 ng/mL	151 (92.1)	88 (75.9)	< 0.001
	> 400 ng/mL	13 (7.9)	28 (24.1)
PET/CT, n (%)	Negative	164 (100)	26 (22.4)	< 0.001
	Positive	0 (0)	90 (77.6)
Pretransplant therapy, n (%)	No therapy	39 (23.8)	29 (25)	0.77
	Surgery only	8 (4.9)	4 (3.4)
	TACE only	71 (43.3)	52 (44.8)
	RFA only	7 (4.3)	2 (1.7)
	Combination	39 (23.8)	29 (25)
Viral hepatitis, n (%)	HBV	142 (86.6)	103 (88.8)	0.442
	HCV	9 (5.5)	8 (6.9)
	NBNC	11 (6.7)	3 (2.6)
	HBV + HCV	2 (1.2)	2 (1.7)
Differentiation1, n (%)	I-II	102 (62.2)	55 (47.4)	0.02
	III-IV	62 (37.8)	61 (52.6)
Microvascular invasion, n (%)	Absent	127 (77.4)	47 (40.5)	< 0.001
	Present	37 (22.6)	69 (59.5)
Capsule formation, n (%)	No complete	134 (81.7)	94 (81)	1
	Complete	30 (18.3)	22 (19)
Ductal invasion, n (%)	Absent	161 (98.2)	109 (94)	0.123
	Present	3 (1.8)	7 (6)
Serosal invasion, n (%)	Absent	146 (89)	72 (62.1)	< 0.001
	Present	18 (11)	44 (37.9)
Intrahepatic metastasis, n (%)	Absent	129 (78.7)	55 (47.4)	< 0.001
	Present	35 (21.3)	61 (52.6)
Cirrhosis, n (%)	Absent	10 (6.1)	11 (9.5)	0.407
	Present	154 (93.9)	105 (90.5)
Dysplastic nodule, n (%)	Absent	120 (73.2)	81 (69.8)	0.633
	Present	44 (26.8)	35 (30.2)

¹Edmondson-Steiner Grade. HBV: Hepatitis B virus; HCV: Hepatitis C virus; NBNC: Non-hepatitis B and non-hepatitis C virus; B + C: Hepatitis B and C virus; NCCK: National Cancer Center Korea; TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation; PET/CT: Positron emission tomography/computed tomography; AFP: α-fetoprotein; MELD: Model for End-Stage Liver Disease; SUV: Standardized uptake value.

Table 3 Comparison between preoperative imaging and explant pathology by the Milan and National Cancer Center Korea criteria

Milan criteria		NCCK criteria		Preoperative imaging
				Within	Beyond
Explant	Within			120 (42.86)	12 (4.29)
Pathology	Beyond			47 (16.79)	101 (36.07)
		Explant	Within	161 (57.50)	3 (1.07)
		Pathology	Beyond	17 (6.07)	99 (35.36)

Cohen’s Kappa = 0.850. NCCK: National Cancer Center Korea.

Table 4 Area under the curves and 95%CI for the Milan, University of California, San Francisco, and National Cancer Center Korea criteria for the prediction of 1, 3, and 5 years disease-free survival

Diagnostic approach	Criteria	AUC (95%CI)
		1 yr	3 yr	5 yr
Preoperative	Milan1	0.814	0.804	0.799
imaging		(0.754, 0.873)	(0.750, 0.858)	(0.747, 0.851)
	UCSF2	0.812	0.800	0.793
		(0.754, 0.871)	(0.747, 0.853)	(0.741, 0.844)
	NCCK3	0.810	0.806	0.802
		(0.753, 0.867)	(0.755, 0.857)	(0.753, 0.852)
Explant pathology	Milan4	0.824	0.815	0.807
		(0.767, 0.880)	(0.764, 0.866)	(0.757, 0.856)
	UCSF5	0.819	0.811	0.803
		(0.761, 0.877)	(0.759, 0.863)	(0.752, 0.853)
	NCCK6	0.823	0.817	0.810
		(0.769, 0.878)	(0.767, 0.866)	(0.762, 0.857)

¹Adjusted by PET, X, Y and Z;

²By PET, X and Y;

³By maximum tumor size, X, Y, and Z;

⁴By PET, total tumor size, X and Y;

⁵By PET, X, Y, and Z;

⁶By total tumor size, X, Y, and Z. X: Microvascular invasion; Y: Major vessel invasion; Z: Intrahepatic metastasis; AUC: Area under the curves; UCSF: University of California, San Francisco; PET: Positron emission tomography; NCCK: National Cancer Center Korea; 95%CI and P value were calculated by Cox PH regression analyses adjusted by the following covariates for each criteria.