Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging

Table 1 Baseline characteristics in training, test, and validation sets for predicting vessels encapsulating tumor clusters, n (%)

Characteristic	Training set (n = 177)			Test set (n = 78)		Validation set (n = 54)
	VETC negative (n = 91)	VETC positive (n = 86)	P value	VETC negative (n = 37)	VETC positive (n = 41)	VETC negative (n = 26)	VETC positive (n = 28)
Clinical features
Age	55.960 ± 10.102	54.350 ± 11.541	0.323	54.590 ± 9.494	58.510 ± 12.386	56.270 ± 10.294	58.930 ± 8.675
Gender			0.578
Male	71 (40.1)	70 (39.5)		32 (41.0)	36 (46.2)	22 (40.7)	22 (40.7)
Female	20 (11.3)	16 (9.0)		5 (6.4)	5 (6.4)	4 (7.4)	6 (11.1)
Liver disease			0.750
HAV	0 (0.0)	1 (0.6)		0 (0)	0 (0.0)	0 (0.0)	0 (0.0)
HBV	77 (43.5)	75 (42.4)		35 (44.9)	37 (47.4)	19 (35.2)	25 (46.3)
HCV	3 (1.7)	2 (1.1)		0 (0.0)	0 (0.0)	2 (3.7)	0 (0.0)
None	11 (6.2)	8 (4.5)		2 (2.6)	4 (5.1)	5 (9.3)	3 (5.6)
AFP-L3			0.886
Negative	69 (39.0)	66 (37.3)		28 (35.9)	34 (43.6)	20 (37.0)	21 (38.9)
Positive	22 (12.4)	20 (11.3)		9 (11.5)	7 (9.0)	6 (11.1)	7 (13.0)
AFP_lg10	1.07 (0.49-2.05)	1.48 (0.92-2.36)	0.009	1.10 (0.64-1.85)	1.47 (0.85-2.45)	1.23 (0.69-1.90)	1.95 (0.90-2.64)
PIVKA-II (mAU/mL)	50 (27.00-194.05)	83 (28.00-213.75)	0.635	41 (24.5-135.5)	88 (31.00-193.52)	58 (27.75-321.5)	60 (23.00-295.75)
CA199 (U/mL)	12.6 (7.6-21.7)	17.85 (7.4-32.5)	0.003	16.7 (10.6-27.6)	19.6 (10.4-28.9)	18.66 (9.4-29.4)	28.3 (13.6-49.4)
HBsAg			0.621
Negative	14 (7.9)	11 (6.2)		2 (2.6)	6 (7.7)	7 (13.0)	4 (7.4)
Positive	77 (43.5)	75 (42.4)		35 (44.9)	35 (44.9)	19 (35.2)	24 (44.4)
HBV/C-DNA, IU/mL			0.083
< 50	55 (31.1)	37 (20.9)		20 (25.6)	23 (29.5)	15 (27.8)	17 (31.5)
50-103	10 (5.6)	17 (9.6)		8 (10.3)	7 (9.0)	6 (11.1)	3 (5.6)
103-105	14 (7.9)	13 (7.3)		4 (5.1)	5 (6.4)	3 (5.6)	4 (7.4)
> 105	12 (6.8)	19 (10.7)		5 (6.4)	6 (7.7)	2 (3.7)	3 (5.6)
MRI features
Tumor diameter (cm)	2.151 ± 0.590	2.185 ± 0.560	0.689	2.089 ± 0.590	2.083 ± 0.620	2.371 ± 0.600	2.086 ± 0.600
Tumor number			0.894
Solitary	82 (46.3)	78 (44.1)		33 (42.3)	38 (48.7)	26 (48.1)	25 (46.3)
Multiple	9 (5.1)	8 (4.5)		4 (5.1)	3 (3.8)	0 (0.0)	3 (5.6)
Shape			0.004
Regular	54 (30.5)	32 (18.1)		17 (21.8)	15 (19.2)	22 (40.7)	15 (27.8)
Irregular	37 (20.9)	54 (30.5)		20 (25.6)	26 (33.3)	4 (7.4)	13 (24.1)
Margin			0.003
Smooth	52 (29.4)	30 (16.9)		22 (28.2)	8 (10.3)	21 (38.9)	15 (27.8)
Non-smooth	39 (22.0)	56 (31.6)		15 (19.2)	33 (42.3)	5 (9.3)	13 (24.1)
Radiological capsule enhancement			0.231
Complete	25 (14.1)	33 (18.6)		11 (14.1)	6 (7.7)	17 (31.5)	13 (24.1)
Incomplete	49 (27.7)	36 (20.3)		16 (20.5)	27 (34.6)	4 (7.4)	9 (16.7)
Absent	17 (9.6)	17 (9.6)		10 (12.8)	8 (10.3)	5 (9.3)	6 (11.1)
Restricted diffusion			0.276
Present	88 (49.7)	80 (45.2)		36 (46.2)	35 (44.9)	25 (46.3)	28 (51.9)
Absent	3 (1.7)	6 (3.4)		1 (1.3)	6 (7.7)	1 (1.9)	0 (0.0)
Non-rim APHE			0.689
Present	67 (37.9)	61 (34.5)		23 (29.5)	28 (35.9)	24 (44.4)	24 (44.4)
Absent	24 (13.6)	25 (14.1)		14 (17.9)	13 (16.7)	2 (3.7)	4 (7.4)
Rim APHE			0.037
Absent	27 (15.3)	14 (7.9)		24 (30.8)	32 (41.0)	24 (44.4)	22 (40.7)
Present	64 (36.2)	72 (40.7)	Present	13 (16.7)	9 (11.5)	2 (3.7)	6 (11.1)
Arterial peritumoral enhancement			< 0.001
Absent	83 (46.9)	52 (29.4)		34 (43.6)	27 (34.6)	22 (40.7)	15 (27.8)
Present	8 (4.5)	34 (19.2)		3 (3.8)	14 (17.9)	4 (7.4)	13 (24.1)
Nonperipheral “washout”			0.823
Present	61 (34.5)	59 (33.3)		21 (26.9)	29 (37.2)	19 (35.2)	22 (40.7)
Absent	30 (16.9)	27 (15.3)		16 (20.5)	12 (15.4)	7 (13.0)	6 (11.1)
Enhancement pattern			0.832
Typical	60 (33.9)	58 (32.8)		20 (25.6)	28 (35.9)	19 (35.2)	22 (40.7)
Atypical	31 (17.5)	28 (15.8)		17 (21.8)	13 (16.7)	7 (13.0)	6 (11.1)

Unless otherwise noted, data are number of patients with percentages in parentheses, median with interquartile range in parenthesis, or the mean with standard deviation in parenthesis. The P value of the training set was calculated by univariable logistic regression. VETC: Vessels encapsulating tumor clusters; AFP: Alpha-fetoprotein; CA199: Carbohydrate antigen 199; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HBV/C-DNA: Quantitation of hepatitis B virus genomic DNA; APHE: Arterial phase hyperenhancement; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; HBsAg: Hepatitis B surface antigen.

Table 2 Univariate and multivariate logistic regression analyses in training set for predicting vessels encapsulating tumor clusters

Variable	Univariable logistic regression			Multivariable logistic regression
	OR	95%CI	P value	OR	95%CI	P valuea
HBV/C-DNA (IU/mL)			0.083
50-103	2.527	1.043, 6.125	0.040
103-105	0.464	0.583, 3.269	0.464
> 105	2.354	1.022, 5.421	0.044
AFP_Lg10	1.607	1.126, 2.293	0.009	1.857	1.212, 2.845	0.004
CA199	1.033	1.011, 1.055	0.003	1.035	1.010, 1.061	0.006
Shape (Irregular)	2.463	1.345, 4.511	0.004	3.881	1.750, 8.609	0.001
Margin (non-smooth)	2.489	1.356, 4.569	0.003	3.409	1.526, 7.616	0.003
Arterial peritumoral enhancement (present)	6.784	2.915, 15.786	< 0.001	4.679	1.847, 11.853	0.001

^aP < 0.05 indicates a significant difference between vessels encapsulating tumor clusters (VETC)-positive and -negative hepatocellular carcinoma (HCC) in multivariable logistic regression.

OR: Odds ratio; CI: Confidence interval; VETC: Vessels encapsulating tumor clusters; HBV/C-DNA: Quantitation of hepatitis B virus genomic DNA; AFP: Alpha-fetoprotein; CA199: Carbohydrate antigen 199.

Table 3 Model performance in training, test, and validation sets for predicting vessels encapsulating tumor clusters

	Training	Test	Validation
AUC	0.811 (0.749, 0.873)	0.800 (0.702, 0.898)	0.791 (0.669, 0.914)
Accuracy	0.734	0.705	0.722
Sensitivity	0.674	0.683	0.750
Specificity	0.813	0.811	0.769

AUC: Area under the curve.