Novel Prognostic Nomogram to Predict Progression-Free Survival of Patients with Hepatocellular Carcinoma After Transarterial Chemoembolization

Figures & data

Table 1 Baseline Characteristics of the Enrolled Patients

Characteristics (n=346)	Baseline	1 Month After Initial TACE	12 Months After Initial TACE	P*	P^#
Age (y)	53±12	–	–	–	–
Gender (male, (%))	304(87.9%)	–	–	–	–
Aetiology
HBV, (%)	330(95.4)	–	–	–	–
HCV, (%)	14(4.0)	–	–	–	–
Others, (%)	2(0.6)	–	–	–	–
WBC (10^9/L)	5.9(4.4–8.1)	7.4(5.8–10.7)	5.7(5.0–9.8)	0.029	0.831
NLR	3.1(2.3–5.1)	7.3(5.6–10.8)	4.6(2.1–7.3)	<0.001	0.021
Hb (g/L)	131(123–148)	112(90–131)	124(112–143)	0.044	0.570
PLT (10^9/L)	158(100–202)	135(95–210)	145(121–188)	0.720	0.033
ALT (U/L)	36.6(22.9–68.3)	36.5(20.0–79.1)	45.2(26.2–64.3)	0.903	0.388
AST (U/L)	48.9(30.7–88.8)	33.6(28.7–60.0)	40.1(25.1–76.3)	0.012	0.076
γ-GT (U/L)	112.2(61.4–230.3)	97.4(54.1–176.5)	123.6(43.6–210.5)	0.056	0.357
ALP (U/L)	127.6(95.3–210.1)	110.2(78.1–190.5)	125.0(88.1–245.4)	0.033	0.684
ALB (g/L)	39.4(34.0–44.4)	35.4(29.6–40.3)	29.2(25.1–35.9)	0.041	0.029
TBIL (μmol/L)	12.6(7.3–24.9)	13.7(6.1–18.8)	24.4(10.3–42.8)	0.890	0.008
ALBI (%)				<0.001	<0.001
1	222(64.2)	128(37.0)	167(48.3)
2	102(29.4)	182(52.6)	146(42.2)
3	22(6.4)	36(10.4)	33(9.5)
PT (s)	14.4(13.5–15.7)	15.3(12.2–15.9)	13.4(12.1–16.4)	0.110	0.991
PTA (%)	80.3(74.1–92.7)	76.2(72.1–85.3)	75.2(72.6–93.2)	0.630	0.402
AFU (IU/L)	34.5(30.6–44.2)	30.2(25.4–40.1)	23.0(19.3–34.7)	0.780	0.670
AFP (ng/mL)	846.7(78.9–6016.5)	476.3(44.6–2056.4)	532.2(116.5–4154.0)	<0.001	0.003
DCP (mAU/mL)	412.6(70.0–11,032.2)	101.3(67.1–4366.2)	313.1(92.1–6575.4)	<0.001	<0.001
CA199(U/mL)	31.8(13.1–82.8)	23.9(10.4–58.7)	26.4(11.6–77.6)	0.101	0.652
CEA (ng/mL)	3.6(2.1–6.7)	2.3(1.7–7.1)	3.0(2.5–5.7)	0.065	0.105
Tumour number, (%)
Solitary	70(20.2)	–	–	–	–
Multiple	276(79.8)	–	–	–	–
PVTT, (%)
Yes	87(25.1)	–	–	–	–
No	259(74.9)	–	–	–	–
BCLC, (%)
A	13(3.8)	–	–	–	–
B	246(71.1)	–	–	–	–
C	87(25.1)	–	–	–	–

Notes: *P: the 1-month follow-up data were analysed and compared with the baseline data, ^#P: the 12-month follow-up data were analysed and compared with the baseline data.

Abbreviations: TACE, transarterial chemoembolization; HBV, hepatitis B virus; HCV, hepatitis C virus; WBC, white blood cell; NLR, Neutrophil to Lymphocyte Ratio; Hb, Hemoglobin; PLT, Platelet; ALT, alanine aminotransferase; AST, aspartate transaminase; γ-GT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TBIL, total bilirubin; ALBI, albumin-bilirubin; PT, prothrombin time; PTA, prothrombin time activity; AFU, alpha-L-fucosidase; AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; PVTT, portal vein tumour thrombus; BCLC, Barcelona Clinic Liver Cancer. n, number; y, year; L, liter; g, gram; U, unit; s, second; IU, international unit; ng, nanogram; mL, mini liter; mAU, Milli Absorbance Units.

Table 2 Characteristics of the Derivation Cohort and Validation Cohort at Baseline

Characteristics	Derivation Cohort (n=208)	Validation Cohort (n=138)	P
Age (y)	54±12	53±12	0.583
Gender (male, (%))	185(88.9)	119(86.2)	0.518
Aetiology			0.829
HBV, (%)	199(95.7)	131(94.9)
HCV, (%)	9(4.3)	5(3.7)
Others, (%)	–	2(1.4)
WBC (10^9/L)	5.7(4.7–8.4)	6.3(4.5–8.9)	0.827
NLR	2.9(2.4–4.7)	3.1(2.5–5.0)	0.266
Hb (g/L)	129(121–146)	137(123–149)	0.722
PLT (10^9/L)	160(111–207)	167(103–203)	0.270
ALT (U/L)	32.5(23.1–70.4)	37.6(25.3–76.8)	0.757
AST (U/L)	50.1(30.2–88.5)	48.3(32.7–90.5)	0.252
γ-GT (U/L)	115.2(65.3–234.3)	110.1(59.2–238.0)	0.079
ALP (U/L)	123.5(97.9–190.7)	131.2(101.0–212.6)	0.604
ALB (g/L)	37.5(33.1–45.8)	36.8(30.2–44.4)	0.441
TBIL (μmol/L)	11.7(6.8–26.1)	12.7(8.9–25.2)	0.267
ALBI, (%)			0.604
1	135(64.9)	87(63.0)
2	58(27.9)	44(31.9)
3	15(7.2)	7(5.1)
PT (s)	14.1(13.6–15.4)	14.2(13.0–16.5)	0.456
PTA (%)	79.2(73.1–88.5)	80.0(71.0–93.0)	0.139
AFU (IU/L)	31.0(29.0–43.0)	33.0(31.7–47.0)	0.173
AFP (ng/mL)	865.4(80.3–7156.3)	814.3(77.5–6492.0)	0.332
DCP (mAU/mL)	434.6(65.3–11,654.4)	399.0(92.8–17,730.0)	0.490
CA199(U/mL)	29.0(12.7–77.5)	31.7(15.3–85.3)	0.106
CEA (ng/mL)	3.2(2.0–6.4)	3.3(1.8–7.1)	0.288
Tumour number, (%)			0.902
Solitary	43(20.7)	27(19.6)
Multiple	165(79.3)	111(80.4)
PVTT, (%)			0.531
Yes	50(24.0)	37(26.8)
No	158(76.0)	101(73.2)
BCLC, (%)			0.691
A	8(3.8)	5(3.6)
B	150(72.1)	96(69.6)
C	50(24.1)	37(26.8)

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; WBC, white blood cell; NLR, Neutrophil to Lymphocyte Ratio; Hb, Hemoglobin; PLT, Platelet; ALT, alanine aminotransferase; AST, aspartate transaminase; γ-GT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; ALB, albumin; TBIL, total bilirubin; ALBI, albumin-bilirubin; PT, prothrombin time; PTA, prothrombin time activity; AFU, alpha-L-fucosidase; AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen; PVTT, portal vein tumour thrombus; BCLC, Barcelona Clinic Liver Cancer.

Table 3 Prognostic Factors Associated with PFS After TACE in Patients with HCC

Characteristics (n=208)	HR (95% CI)	P
Baseline characteristics
AGE (y)
≤ 53
> 53	2.104(1.327–3.076)	0.013
ALBI
1
2	1.977(1.215–3.712)	0.029
3	2.011(1.664–2.871)	<0.001
PVTT
No
Yes	2.541(1.662–3.491)	<0.001
Indicators of 1 month after initial TACE
NLR
≤4.4
>4.4	1.675(1.475–2.396)	0.032
AFP*
0
1	2.065(1.568–3.715)	0.015
2	2.224(1.456–3.585)	0.005
DCP*
0
1	3.343(1.790–5.95)	<0.001
2	3.669(2.471–5.877)	<0.001
The number of TACE in 6 months
<3
≥3	0.387(0.134–0.521)	0.007

Notes: *Compared with baseline, 0 indicates there was a change of decrease ≥20% in the outcome of the follow-up visit; 2 indicates there was a change of increase ≥20%; 1 indicates the change in the index follow-up outcome was between 0 and 2.

Abbreviations: PFS, progression-free survival; TACE, transarterial chemoembolization, HCC, hepatocellular carcinoma; ALBI, albumin-bilirubin; PVTT, portal vein tumour thrombus; NLR, Neutrophil to Lymphocyte Ratio; AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin.

Figure 1 A prognostic nomogram for PFS in patients with HCC after TACE. The nomogram included baseline indicators: Age, ALBI, PVTT; indicators of 1 month follow-up: NLR, the change of AFP and DCP; and the cumulative number of TACE in 6 months. *Compared with baseline, 0 indicates there was a change of decrease ≥20% in the outcome of the follow-up visit; 2 indicates there was a change of increase ≥20%; 1 indicates the change in the index follow-up outcome was between 0 and 2.

Abbreviations: ALBI, albumin-bilirubin; PVTT, portal vein tumour thrombus; NLR, Neutrophil to Lymphocyte Ratio; AFP, alpha-fetoprotein; DCP, des-γ-carboxy prothrombin; TACE, transarterial chemoembolization.

Figure 2 The calibration curves of the nomogram in the derivation and validation cohorts. (A) derivation cohort, (B) validation cohort. The nomogram-predicted probability of PFS is plotted on the x-axis, and the actual PFS is plotted on the y-axis.

Table 4 Comparison of the Concordance Index Between the Constructed Nomogram and BCLC Stage for PFS Prediction in the Derivation and Validation Cohorts

	Derivation Cohort		Validation Cohort
	C-Index (95% CI)	P	C-Index (95% CI)	P
Nomogram	0.712(0.533–0.931)		0.734 (0.636–0.842)
BCLC	0.688(0.542–0.867)		0.663(0.525–0.791)
Nomogram vs BCLC		0.004		0.012

Abbreviations: BCLC, Barcelona Clinic Liver Cancer; PFS, progression-free survival.

Figure 3 The ROC curve of the nomogram and BCLC for predicting 12-month PFS in the derivation and validation cohorts. The ROC curve of the (A) nomogram in the derivation cohort, (B) BCLC in the derivation cohort, (C) nomogram in the validation cohort, and (D) BCLC in the validation cohort, for predicting 12-month PFS.

Abbreviation: AUC, area under curve.

Data Sharing Statement

All data in the study are included in the published article.