Habitat imaging on contrast-enhanced magnetic resonance imaging predicts early response to transarterial chemoembolization in hepatocellular carcinoma

Table 1 Baseline characteristics of all cohorts, n (%)

Features	Training cohort (n = 107)	Validation cohort (n = 46)	External validation cohort (n = 70)	P value
Age (years), mean ± SD	63.24 ± 11.72	61.80 ± 13.07	65.74 ± 9.59	0.160
Sex				0.791
Male	87 (81.3)	37 (80.4)	54 (77.1)
Female	20 (18.7)	9 (19.6)	16 (22.9)
Size > 5 cm				0.427
Yes	44 (41.1)	17 (37.0)	22 (31.4)
No	63 (58.9)	29 (63.0)	48 (68.6)
Tumor number				0.168
Single	39 (36.4)	17 (37.0)	35 (50.0)
Multiple	68 (63.6)	29 (63.0)	35 (50.0)
Vascular tumor thrombus				0.154
Yes	35 (32.7)	11 (23.9)	14 (20.0)
No	72 (67.3)	35 (76.1)	56 (80.0)
Cirrhosis				0.187
Yes	77 (72.0)	28 (60.9)	42 (60.0)
No	30 (28.0)	18 (39.1)	28 (40.0)
ALP > 125 U/L				0.785
Yes	43 (40.2)	19 (41.3)	25 (35.7)
No	64 (59.8)	27 (58.7)	45 (64.3)
AFP > 400 ng/mL				0.609
Yes	24 (22.4)	11 (23.9)	12 (17.1)
No	83 (77.6)	35 (76.1)	58 (82.9)
AST > 40 U/L				0.178
Yes	63 (58.9)	30 (65.2)	34 (48.6)
No	44 (41.1)	16 (34.8)	36 (51.4)
ALT > 50 U/L				0.836
Yes	31 (29.0)	14 (30.4)	18 (25.7)
No	76 (71.0)	32 (69.6)	52 (74.3)
TBIL < 19 μmol/L				0.562
Yes	56 (52.3)	24 (52.2)	42 (60.0)
No	51 (47.7)	22 (47.8)	28 (40.0)
ALB > 40 g/L				0.087
Yes	21 (19.6)	13 (28.3)	24 (34.3)
No	86 (80.4)	33 (71.7)	46 (65.7)
History of hepatitis B				0.432
Yes	89 (83.2)	41 (89.1)	56 (80.0)
No	18 (16.8)	5 (10.9)	14 (20.0)
ECOG				0.673
0	88 (82.2)	41 (89.1)	60 (85.7)
1	14 (13.1)	4 (8.7)	9 (12.9)
2	5 (4.7)	1 (2.2)	1 (1.4)
BCLC				0.369
0	4 (3.7)	1 (2.2)	6 (8.6)
A	37 (34.6)	18 (39.1)	29 (41.4)
B	24 (22.4)	14 (30.4)	17 (24.3)
C	40 (37.4)	11 (23.9)	17 (24.3)
D	2 (1.9)	2 (4.3)	1 (1.4)
Child-Pugh				0.102
A	61 (57.0)	29 (63.0)	53 (75.7)
B	44 (41.1)	15 (32.6)	16 (22.9)
C	2 (1.9)	2 (4.3)	1 (1.4)

ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; TBIL: Total bilirubin; ALB: Albumin; ECOG: Eastern Cooperative Oncology Group; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Univariable and multivariable logistic regression analysis of clinical features

Features	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)1	P value
Sex	0.886 (0.390-2.010)	0.771
Age	1.002 (0.976-1.029)	0.879
Tumor size	0.177 (0.088-0.355)	< 0.001	0.370 (0.180-0.760)	0.0066
Tumor number (multiple)	0.411 (0.212-0.805)	0.009	0.390 (0.180-0.820)	0.0136
Tumor thrombus	0.503 (0.266-0.971)	0.044
Liver cirrhosis	0.686 (0.341-1.379)	0.290
ALP (> 125 U/L)	0.120 (0.058-0.251)	< 0.001	0.280 (0.130-0.600)	< 0.001
AFP (> 400 ng/mL)	0.779 (0.365-1.659)	0.517
Hepatitis B history	0.642 (0.255-1.618)	0.347
ECOG PS	0.352 (0.162-0.741)	0.007
BCLC stage	0.690 (0.488-0.975)	0.035
AST (> 40 U/L)	0.692 (0.358-1.340)	0.275
ALT (> 50 U/L)	1.095 (0.542-2.211)	0.801
Total bilirubin (< 19 μmol/L)	1.382 (0.728-2.623)	0.323
Albumin (> 40 g/L)	0.844 (0.393-1.813)	0.663
Child-Pugh class	0.311 (0.151-0.667)	0.002

¹Empty cells indicate the variable was not included in the multivariate regression model or had no statistical significance in multivariate analysis.

OR: Odds ratio; CI: Confidence interval; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; ECOG PS: Eastern Cooperative Oncology Group performance status; BCLC: Barcelona Clinic Liver Cancer; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 3 Prediction performance of different models

Models	Accuracy	AUC	95%CI	Sensitivity	Specificity	Precision1	F12	Cohort
Clinical model	0.79	0.86	0.78-0.93	0.77	0.82	0.84	0.80	Train
Radiomics model	0.69	0.71	0.60-0.82	0.73	0.63	0.71	0.72	Train
ITH model	0.85	0.89	0.81-0.96	0.79	0.92	0.93	0.85	Train
ITH + clinical model	0.90	0.95	0.90-0.99	0.90	0.90	0.92	0.91	Train
ITH + radiomics model	0.87	0.93	0.87-0.98	0.85	0.90	0.91	0.88	Train
Radiomics + clinical model	0.85	0.90	0.82-0.96	0.92	0.76	0.83	0.87	Train
Combined model	0.90	0.97	0.93-0.99	0.88	0.92	0.93	0.90	Train
Clinical model	0.80	0.78	0.54-0.98	0.75	0.89	0.90	0.82	Validation
Radiomics model	0.67	0.66	0.39-0.89	0.58	0.78	0.78	0.67	Validation
ITH model	0.87	0.90	0.74-1.00	0.75	1.00	1.00	0.86	Validation
ITH + clinical model	0.91	0.88	0.64-1.00	1.00	0.78	0.86	0.92	Validation
ITH + radiomics model	0.87	0.91	0.75-1.00	0.83	0.89	0.91	0.87	Validation
Radiomics + clinical model	0.76	0.68	0.42-0.92	0.75	0.78	0.82	0.78	Validation
Combined model	0.91	0.91	0.71-1.00	0.92	0.89	0.92	0.92	Validation
Clinical model	0.41	0.54	0.33-0.75	0.37	0.75	0.92	0.53	External validation
Radiomics model	0.87	0.78	0.57-0.96	0.90	0.63	0.95	0.93	External validation
ITH model	0.71	0.87	0.77-0.96	0.68	1.00	1.00	0.81	External validation
ITH + clinical model	0.71	0.89	0.78-0.97	0.68	1.00	1.00	0.81	External validation
ITH + radiomics model	0.86	0.94	0.88-0.99	0.84	1.00	1.00	0.91	External validation
Radiomics + clinical model	0.89	0.78	0.56-0.98	0.92	0.63	0.95	0.93	External validation
Combined model	0.83	0.93	0.87-0.99	0.81	1.00	1.00	0.89	External validation

¹Positive predictive value (proportion of true positives among predicted positives).

²Harmonic mean of precision and sensitivity, balancing both metrics.

ITH: Intratumoral heterogeneity; AUC: Area under the curve; CI: Confidence interval.