Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma

Table 1 Baseline characteristics of patients with combined hepatocellular carcinoma and cholangiocarcinoma in the training and validation sets

Variable	Entire cohort (n = 118)	Training set (n = 84)	Validation set (n = 34)	P value
Male sex	102 (86.4)	73 (86.9)	29 (85.3)	0.817
Age, yr	51.6 ± 10.5	51.2 ± 10.5	52.7 ± 10.6	0.484
Hypertension	11 (9.3)	7 (8.3)	4 (11.8)	0.561
Diabetes mellitus	7 (5.9)	6 (7.1)	1 (2.9)	0.382
Hepatitis B/C	61 (51.7)	40 (47.6)	21 (61.8)	0.164
Child-Pugh, A/B	116/2	83/1	33/1	0.495
Liver cirrhosis	47 (39.8)	35 (41.7)	12 (35.3)	0.522
Hypersplenia	15 (12.7)	11 (13.1)	4 (11.8)	0.844
ALT (U/L)	55.2 ± 100.4	46.1 ± 29.3	77.6 ± 181.1	0.807
AST (U/L)	59.8 ± 136.6	48.1 ± 28.8	88.6 ± 250.7	0.513
ALB (g/L)	42.1 ± 4.6	42.3 ± 4.0	41.5 ± 5.7	0.643
TB (mmol/L)	15.9 ± 10.1	15.7 ± 10.1	16.5 ± 10.0	0.597
AFP (ng/mL)	285.2 ± 475.1	256.3 ± 454.6	356.5 ± 522.4	0.156
CA19-9 (U/mL)	106.8 ± 251.2	109.7 ± 258.3	99.6 ± 236.2	0.184
CA125 (U/mL)	117.0 ± 624.6	152.9 ± 727.5	18.3 ± 11.9	0.541
CEA (ng/mL)	6.4 ± 30.3	7.5 ± 35.5	3.4 ± 3.2	0.444
Liver fibrosis				0.871
No significant fibrosis	15 (13.8)	11 (13.8)	4 (13.8)
Significant fibrosis	37 (33.9)	26 (32.5)	11 (37.9)
Advanced fibrosis	57 (52.3)	43 (53.8)	14 (48.3)
Not mentioned	8 (6.8)	3 (3.6)	5 (14.7)
Tumor size, ≤ 5 cm	38 (32.2)	20 (23.8)	18 (52.9)	0.002
Tumor number, ≥ 2	67 (56.8)	52 (61.9)	15 (44.1)	0.077
Satellite lesions	42 (35.6)	29 (34.5)	13 (38.2)	0.703
Vascular invasion	46 (39.0)	35 (41.7)	11 (32.4)	0.347
Lymph node infiltration	15 (12.7)	10 (11.9)	5 (14.7)	0.679
Differentiation				0.578
Well	44 (37.3)	30 (35.7)	14 (41.2)
Moderate	22 (18.6)	18 (21.4)	4 (11.8)
Poor	1 (0.8)	1 (1.2)	0 (0.0)
Undifferentiated	51 (43.2)	35 (41.7)	16 (47.1)
8th AJCC stage				0.027
I	9 (7.6)	7 (8.3)	2 (5.9)
II	28 (23.7)	14 (16.7)	14 (41.2)
III	66 (55.9)	53 (63.1)	13 (38.2)
IV	15 (12.7)	10 (11.9)	5 (14.7)
T stage				0.042
T1	13 (11.0)	9 (10.7)	4 (11.8)
T2	29 (24.6)	15 (17.9)	14 (41.2)
T3	45 (38.1)	37 (44.0)	8 (23.5)
T4	31 (26.3)	23 (27.4)	8 (23.5)
N stage				0.762
N0	103 (87.3)	74 (88.1)	29 (85.3)
N1	15 (12.7)	10 (11.9)	5 (14.7)
Transfusion	17 (14.4)	14 (16.7)	3 (8.8)	0.388
Blood loss ≤ 400 mL	71 (60.2)	49 (58.3)	22 (64.7)	0.522
Margin, R1	13 (11.0)	9 (10.7)	4 (11.8)	0.869
Surgical method				0.285
Major resection	57 (48.3)	44 (52.4)	13 (38.2)
Minor resection	50 (42.4)	32 (38.1)	18 (52.9)
Resection + ablation	11 (9.3)	8 (9.5)	3 (8.8)
Anatomical resection	50 (43.9)	39 (48.1)	11 (33.3)	0.148
Postoperative TACE	35 (29.7)	28 (33.3)	7 (20.6)	0.17
Hospital stay (d)	12.2 ± 4.5	12.3 ± 4.4	11.9 ± 5.0	0.608
Overall survival (mo)	30.8 ± 26.3	29.6 ± 26.2	33.6 ± 26.9	0.462

¹Values are n, n (%), or mean ± SD, unless otherwise noted.

AFP: Alpha fetoprotein; AJCC: American Joint Committee on Cancer; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CEA: Carcinoembryonic antigen; TACE: Transhepatic arterial chemotherapy and embolization; TB: Total bilirubin.

Table 2 Univariate analysis and multivariate Cox regression to identify clinical factors associated with overall survival after curative hepatectomy

Variable	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
Male sex	0.470 (0.203-1.088)	0.078	1.767 (0.244-1.316)	0.186
Age, yr
≤ 60	Ref.
> 60	1.173 (0.644-2.139)	0.602
Liver cirrhosis
Absent	Ref.
Present	1.370 (0.852-2.203)	0.194
AFP (ng/mL)	0.990 (0.597-1.643)	0.970
CA 19-9 (U/mL)	0.987 (0.586-1.662)	0.960
Albumin (g/L)	2.496 (0.997-6.244)	0.051	1.025 (0.968-1.085)	0.403
TB (μmol/L)
≤ 34	Ref.		Ref.
> 34	17.994 (4.726-68.509)	< 0.001	13.943 (3.561-54.602)	< 0.001
Tumor number, multiple	0.766 (0.473-1.240)	0.277
Satellite lesions
Absent	Ref.		Ref.
Present	2.037 (1.267-3.268)	0.003	1.762 (1.079-2.877)	0.024
Vascular invasion
Absent	Ref.		Ref.
Present	2.009 (1.247-3.239)	0.004	1.725 (1.049-2.834)	0.032
T stage
T1	Ref.
T2	1.171 (0.705-1.942)	0.542
T3	2.424 (0.704-8.348)	0.161
T4	3.823 (1.158-12.615)	0.028
Anatomy resection
Yes	Ref.		Ref.
No	2.011 (1.344-3.006)	0.006	1.731 (1.083-2.767)	0.028
Margin
R0	Ref.
R1	1.032 (0.446-2.387)	0.941
Postoperative TACE
Yes	Ref.
No	1.597 (0.924-2.759)	0.093	1.6051 (0.3546-1.0947)	0.100

AFP: Alpha-fetoprotein; CI: Confidence interval; HR: Hazard ratio; Ref.: Reference; TB: Total bilirubin; TACE: Transhepatic arterial chemotherapy and embolization.

Table 3 Comparison of hazard ratios describing risk for different predictive models

Model	HR (95%CI)	P value
Radiomics score		< 0.001
Low risk	Ref.
High risk	5.908 (3.285-10.626)
Clinical model		< 0.001
Low risk	Ref.
High risk	2.653 (1.532-4.595)
Radiomics nomogram		< 0.001
Low risk	Ref.
High risk	8.155 (4.498-14.785)

CI: Confidence interval; HR: Hazard ratio; Ref.: Reference.