Development of a Prognostic Nomogram in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Following Trans-Arterial Chemoembolization with Drug-Eluting Beads

Figures & data

Table 1 Main Baseline Demographic and Clinical Characteristics of Patients in the Training and Validation Cohorts

Characteristics	Training Cohort (n = 118)	Validation Cohort (n = 82)	P-value
Age (years)			0.782
≤60	60 (50.85%)	44 (53.66%)
>60	58 (49.15%)	38 (46.34%)
Gender			0.053
Male	102 (86.44%)	58 (70.73%)
Female	16 (13.56%)	24 (29.27%)
Cirrhosis			0.975
Yes	88 (74.58%)	61 (74.39%)
No	30 (25.42%)	21 (25.61%)
Preoperative AFP (ng/mL)			0.503
≤400	64 (54.24%)	50 (60.98%)
>400	54 (45.76%)	32 (39.02%)
Preoperative ALT (U/L)			0.503
≤40	64 (54.24%)	50 (60.98%)
>40	54 (45.76%)	32 (39.02%)
Preoperative AST (U/L)			0.913
≤45	22 (18.64%)	16 (19.51%)
>45	96 (81.36%)	66 (80.49%)
Preoperative GGT (U/L)			0.850
≤50	11 (9.32%)	7 (8.54%)
>50	107 (90.68%)	75 (91.46%)
Preoperative TB (μmol/L)			0.280
≤20	56 (47.46%)	30 (36.59%)
>20	62 (52.54%)	52 (63.41%)
Preoperative ALB (g/L)			0.907
<35	88 (74.58%)	62 (75.61%)
≥35	30 (25.42%)	20 (24.39%)
Preoperative PLT (10^9/L)			0.671
<100	23 (19.49%)	18 (21.95%)
≥100	95 (80.51%)	64 (78.05%)
Preoperative PT (seconds)			0.726
≤14	56 (47.46%)	36 (43.90%)
>14	62 (52.54%)	46 (56.10%)
Preoperative INR			0.355
≤1.5	76 (64.41%)	60 (73.17%)
>1.5	42 (35.59%)	22 (26.83%)
Preoperative CP class			0.331
A	96 (81.36%)	60 (73.17%)
B	22 (18.64%)	22 (26.83%)
Tumour number			0.899
≤3	50 (42.37%)	34 (41.46%)
>3	68 (57.63%)	48 (58.54%)
Tumour size (cm)			0.815
≤5	37 (31.36%)	27 (32.93%)
>5	81 (68.64%)	55 (67.07%)
PVTT			0.423
Vp1	21 (17.80%)	18 (21.95%)
Vp2	38 (32.20%)	18 (21.95%)
Vp3	41 (34.75%)	30 (36.59%)
Vp4	18 (15.25%)	16 (19.51%)

Note: Unless otherwise indicated, data are number of patients, with percentages in parentheses.

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CP, Child–Pugh; INR, international normalized ratio; GGT, γ-glutamyl transferase; PLT, platelet count; PT, prothrombin time; PVTT, portal vein tumor thrombosis; TB, total bilirubin.

Table 2 Preoperative Clinical Risk Factors for Overall Survival in Patients with HCC

	Univariable Analysis		Multivariable Analysis
Variable	HR (95% CI)	P	HR (95% CI)	P-value
Age (years)
≤60 vs >60	1.5 (0.75–2.9)	0.25
Gender
Male vs Female	1.9 (0.78–4.6)	0.16
Cirrhosis
Yes vs No	1.3 (0.38–4.1)	0.7
Preoperative AFP (ng/mL)
≤400 vs >400	1.1 (0.54–2.1)	0.87
Preoperative ALT (U/L)
≤40 vs >40	1.1 (0.57–2.2)	0.75
Preoperative AST (U/L)
≤45 vs >45	1.2 (0.51–3)	0.63
Preoperative GGT (U/L)
≤50 vs >50	6.1 (2.5–15)	<0.001	4.67 (1.54–14.13)	0.007
Preoperative TB (μmol/L)
≤20 vs >20	0.72 (0.36–1.4)	0.34
Preoperative ALB (g/L)
<35 vs ≥35	1.1 (0.5–2.3)	0.88
Preoperative PLT (10^9/L)
<100 vs ≥100	2.4 (0.72–7.7)	0.16
Preoperative PT (seconds)
≤14 vs >14	1 (0.53–2)	0.93
Preoperative INR
≤1.5 vs >1.5	1.3 (0.63–2.6)	0.5
Preoperative CP class
A vs B	0.84 (0.32–2.2)	0.72
Tumour number
≤3 vs >3	1.7 (1.2–2.4)	0.003	1.62 (1.10–2.39)	0.016
Tumour size (cm)
≤5 vs >5	1.6 (0.97–2.7)	0.067
PVTT
Vp1–3 vs Vp4	1.5 (1.2–1.9)	<0.001	1.51 (1.02–2.23)	0.04

Note: Data in parentheses are 95% confidence intervals. Bold means that the p value lower than 0.05 is statistically significant.

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; CP, Child–Pugh; INR, international normalized ratio; GGT, γ-glutamyl transferase; HCC, hepatocellular carcinoma; PLT, platelet count; PT, prothrombin time; PVTT, portal vein tumor thrombosis; TB, total bilirubin; HR, hazard ratio; vs, versus.

Table 3 Test the Proportional Hazards Assumption of Clinical Characteristic Using Schoenfeld Residual Test

Covariates	Chi-Square	P-value
GGT	0.4877	0.48
Tumor number	0.6832	0.41
PVTT	0.0119	0.91
Predictive model	1.468	0.69

Abbreviations: GGT, γ-glutamyl transferase; PVTT, portal vein tumor thrombosis.

Figure 1 Visualization of Schoenfeld residual test of proportional hazards assumption for clinical characteristics.

Table 4 The Median Survival Time and Survival Rate According to Risk Stratification

	Train Group		Test Group
	Risk High	Risk Low	Risk High	Risk Low
Median survival time	6.00 (IQR:5.00~8.00)	14.00 (IQR:12.00~17.00)	4.50 (IQR:3.25~8.75)	13.00 (IQR:10.50~16.00)
6-month survival rate	42.8%	88.9%	35.7%	89.0%
12-month survival rate	7.1%	68.9%	21.6%	67.0%
18-month survival rate	0%	51.9%	11.1%	56.8%

Abbreviation: IQR, inter-quartile range.

Figure 2 Kaplan–Meier analysis of risk score with overall survival (OS). (A) Patients with low-risk score (separated by the cut-off value of 2.00) demonstrated significant longer OS compared to patients with high-risk score in the training cohort (p < 0.0001). (B) Patients with low-risk score (≤ 2.00) showed longer OS than patients with high-risk score in the test cohort (p = 0.00014).

Figure 3 A nomogram to predict the 6-, 12- and 18-month survival rates for patients in the training cohort.

Figure 4 ROC curves for the nomogram at 6-, 12- and 18-month in the training cohort (A) and test cohort (B).

Figure 5 Time-dependent ROC curves to show the trend of AUC values over time both in the training and test cohorts.

Figure 6 Calibration curves to evaluate the performance of the nomogram in 6-, 12- and 18-month survival rates in the training (A–C) and test (D–F) cohorts.

Figure 7 Decision curve analysis for overall survival at 6-, 12- and 18-month in the training cohort (A–C) and test cohort (D–F). Black line: All patients dead. Gray line: None patients dead. Blue line: Model of nomogram.