Deep learning-based radiomics based on contrast-enhanced ultrasound predicts early recurrence and survival outcome in hepatocellular carcinoma

Table 1 Patient characteristics

	Study population (n = 414)	Training cohort (n = 289)	Testing cohort (n = 125)	P value
Age, yr	53.00 (45.00- 60.00)	52.059 ± 12.190	53.216 ± 11.380	0.1988
Gender, n (%)
Male	375 (90.6)	262 (90.7)	113 (90.4)	0.9196
BMI, kg/m2	24.50 ± 4.20	24.10 ± 3.20	24.70 ± 3.40	0.1889
HBsAg-positive, n (%)	375 (90.6)	264 (91.3)	111 (88.8)	0.5274
AFP > 7 ng/mL, n (%)	292 (70.5)	205 (70.9)	87 (69.6)	0.8761
CEA > 5 ng/ml, n (%)	31 (7.5)	24 (8.3)	7 (5.6)	0.4494
CA125 > 40 ng/mL, n (%)	15 (3.6)	8 (2.8)	7 (5.6)	0.2588
CA199 > 34 ng/mL, n (%)	46 (11.1)	295 (10.0)	17 (13.6)	0.3738
WBC count, /μL	6262 ± 1985	6232 ± 1756	6354 ± 2125	0.5668
ALT, U/L	49 ± 36	48 ± 39	51 ± 41	0.1654
AST, U/L	51 ± 35	49 ± 36	53 ± 42	0.2358
Liver cirrhosis, n (%)	345 (83.3)	244 (84.4)	101 (80.8)	0.3630
Microvascular invasion, n (%)	312 (75.4)	211 (73.0)	101 (80.8)	0.0910
Tumor size, cm
x	2.40 [1.70-3.68]	2.957 ± 1.850	3.120 ± 2.050	0.3689
y	2.00 [1.42-3.10]	2.480 ± 1.490	2.670 ± 1.960	0.4820
Gray-scale echogenicity				0.5954
Hyperechoic	46 (11.1)	35 (12.1)	11 (8.8)
Medium	4 (1.0)	3 (1.0)	1 (0.8)
Hypoechoic	364 (87.9)	251 (86.9)	113 (90.4)
Arterial phase				0.4639
Hyperenhancement	403 (97.3)	283 (97.9)	120 (96.0)
Isoenhancement	8 (1.9)	4 (1.4)	4 (3.2)
Hypoenhancement	3 (0.7)	2 (0.7)	1 (0.8)
Portal phase				0.6669
Hyperenhancement	15 (3.5)	12 (4.2)	3 (2.4)
Isoenhancement	232 (56.0)	162 (56.1)	70 (56.0)
Hypoenhancement	167 (40.3)	115 (39.8)	52 (41.6)
Late phase				0.1300
Hyperenhancement	2 (0.5)	1 (0.3)	1 (0.8)
Isoenhancement	79 (19.1)	46 (15.9)	33 (90.4)
Hypoenhancement	333 (80.4)	232 (80.3)	101 (80.8)
Enhancing capsules	45 (10.9)	36 (12.5)	9 (7.2)	0.1598
Unsmooth margins	97 (23.4)	64 (22.19)	33 (26.4)	0.4168
Retreatment after recurrence	168 (40.3)	118 (40.5)	50 (40.0)	0.9270

BMI: Body mass index; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; BCLC: Barcelona-clinic liver cancer; WBC: White blood cell; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Univariate and multivariable analyses of early recurrence of hepatocellular carcinoma patients

	Univariate cox regression				Multivariate logistic regression
	HR	[0.025	0.975]	P	HR	[0.025	0.975]	P
Age, yr	0.991	0.971	1.011	0.383
Gender	1.005	0.463	2.181	0.990
HBsAg-positive	1.138	0.472	2.740	0.773
AFP	0.622	0.361	1.071	0.087	0.709	0.406	1.239	0.227
CEA	0.944	0.352	2.535	0.910
CA125	1.811	0.424	7.752	0.423
CA19-9	1.636	0.727	3.684	0.234
ALT, U/L	1.248	0.697	2.321	0.267
AST, U/L	1.566	0.397	2.108	0.675
FIB-4 score	1.212	0.431	1.986	0.742
Liver cirrhosis	1.142	0.506	2.121	0.657
Tumor size x	1.000	0.882	1.143	0.951
Tumor size y	0.988	0.856	1.142	0.873
Gray-scale echogenicity	0.731	0.493	1.087	0.121
Arterial phase enhancement	0.924	0.351	2.438	0.874
Portal phase enhancement	1.321	0.832	2.100	0.238
Portal phase enhancement	0.982	0.512	1.885	0.957
Enhancing capsules	0.930	0.413	2.096	0.862
Satellite nodules	4.843	1.917	12.244	0.001	4.194	1.368	12.871	0.012
Unsmooth margins	0.839	0.462	1.522	0.563
Constant					0.990	0.707	1.387	0.953

Fibrosis-4 score: Age (years) × aspartate aminotransferase (U/L) / [platelet count (10⁹/L) × alanine aminotransferase (U/L)]^1/2. HR: Hazard ratio; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FIB-4 score: Fibrosis-4 score; HBsAg: Hepatitis B surface antigen.

Table 3 Univariate and multivariable analyses of overall survival of hepatocellular carcinoma patients

	Univariate cox regression				Multivariate logistic regression
	HR	[0.025	0.975]	P	HR	[0.025	0.975]	P
Age, yr	1.020	1.000	1.030	0.010	1.02	1.00	1.03	0.01
Gender	1.570	1.030	2.390	0.030	1.42	0.89	2.26	0.14
HBsAg-positive	1.600	1.030	2.490	0.040	1.32	0.82	2.12	0.25
AFP	1.100	0.830	1.460	0.500
CEA	0.760	0.460	1.270	0.300
CA125	0.580	0.280	1.220	0.150
CA19-9	0.630	0.420	0.950	0.030	0.65	0.41	1.03	0.07
ALT, U/L	1.121	0.453	1.976	0.430
AST, U/L	1.342	0.876	2.014	0.540
FIB-4 score	1.012	0.547	1.743	0.720
Liver cirrhosis	1.112	0.563	1.956	0.550
Tumor size x	1.080	1.010	1.160	0.040	0.96	0.85	1.09	0.56
Tumor size y	1.090	1.020	1.170	0.010	1.17	1.02	1.33	0.02
Gray-scale echogenicity	0.830	0.670	1.020	0.080	0.77	0.60	0.99	0.04
Arterial phase enhancement	0.680	0.420	1.110	0.130
Portal phase enhancement	1.270	0.990	1.620	0.060	1.25	0.95	1.63	0.11
Portal phase Enhancement	1.130	0.810	1.580	0.460
Enhancing capsules	1.110	0.720	1.710	0.630
Satellite nodules	1.190	0.780	1.830	0.420
Unsmooth margins	0.720	0.520	0.990	0.040	0.79	0.56	1.13	0.19
Early reoccurrence	1.290	0.990	1.680	0.060	1.25	0.93	1.67	0.14
Retreatment after recurrence	0.710	0.540	1.160	0.300
DLR	3.240	2.670	3.930	< 0.005

HR: Hazard ratio; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA125: Carbohydrate antigen 125; CA19-9: Carbohydrate antigen 19-9; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FIB-4 score: Fibrosis-4 score; DLR: Deep learning-based radiomics.