Nomograms for predicting overall survival and cancer-specific survival in patients with surgically resected intrahepatic cholangiocarcinoma

Figures & data

Table 1 Clinical characteristics of patients in the development cohort and training cohort

Variables	SEER cohort (n=947)	Validation cohort (n=159)	P-value
Gender			0.137
Male	446 (47.10)	85 (53.46)
Female	501 (52.90)	74 (46.54)
Age (years)			0.149
<55	215 (22.70)	35 (22.01)
55–74	569 (60.08)	107 (67.3)
≥75	163 (17.21)	17 (10.69)
Marriage			0.099
Married	603 (63.67)	112 (70.44)
Unmarried	344 (36.33)	47 (29.56)
T stage			0.113
T1a	226 (23.86)	35 (22.01)
T1b	162 (17.11)	25 (15.72)
T2	247 (26.08)	40 (25.16)
T3	184 (19.43)	26 (16.35)
T4	128 (13.52)	33 (20.75)
N stage			0.114
N0	753 (79.51)	135 (84.91)
N1	194 (20.49)	24 (15.09)
M stage			0.222
M0	873 (92.19)	142 (89.31)
M1	74 (7.81)	17 (10.69)
LNR			0.084
<0.17	781 (82.47)	122 (76.73)
≥0.17	166 (17.53)	37 (23.27)
Grade			0.191
Well	115 (12.14)	23 (14.47)
Moderate	517 (54.59)	88 (55.35)
Poor	315 (33.26)	48 (30.19)
Tumor size (cm)
<3.5	237 (25.03)	32 (20.13)
3.5–5.4	244 (25.77)	40 (25.16)
5.5–7.4	202 (21.33)	48 (30.19)
≥7.5	264 (27.88)	39 (24.53)

Abbreviations: LNR, lymph node ratio.

Figure 1 The flowchart of the study cohort.

Table 2 Cumulative OS and CSS in patients with surgically resected ICC

Variable	Cumulative OS				Cumulative CSS
	1-year	3-year	5-year	P-value	1-year	3-year	5-year	P-value
Total	0.807	0.463	0.327		0.886	0.670	0.590
Gender				0.030				0.304
Female	0.829	0.497	0.355		0.890	0.657	0.568
Male	0.782	0.425	0.293		0.873	0.688	0.611
Age (years)				0.013
<55	0.855	0.467	0.338		0.892	0.581	0.480
55–74	0.818	0.497	0.342		0.861	0.644	0.537
≥75	0.707	0.347	0.255		0.804	0.575	0.494
Marriage				0.237				0.907
Married	0.824	0.478	0.323		0.867	0.672	0.604
Unmarried	0.779	0.439	0.332		0.908	0.67	0.566
T stage				<0.001				<0.001
T1a	0.888	0.657	0.496		0.919	0.803	0.691
T1b	0.853	0.615	0.464		0.922	0.741	0.618
T2	0.815	0.459	0.329		0.847	0.631	0.542
T3	0.773	0.267	0.100		0.767	0.458	0.345
T4	0.639	0.216	0.216		0.806	0.352	0.300
N stage				<0.001				<0.001
N0	0.84	0.521	0.388		0.904	0.729	0.654
N1	0.674	0.228	0.077		0.795	0.430	0.310
M stage				<0.001				<0.001
M0	0.829	0.486	0.345		0.872	0.636	0.535
M1	0.55	0.199	0.112		0.689	0.393	0.304
LNR				<0.001				<0.001
<0.17	0.844	0.523	0.381		0.887	0.678	0.578
≥0.17	0.628	0.175	0.075		0.719	0.318	0.229
Grade				<0.001				<0.001
Well	0.874	0.623	0.486		0.911	0.745	0.672
Moderate	0.841	0.506	0.348		0.89	0.662	0.546
Poor	0.724	0.329	0.231		0.783	0.486	0.405
Tumor size (cm)				0.003				<0.001
≤3.5	0.833	0.483	0.376		0.899	0.742	0.667
3.5–5.4	0.834	0.535	0.383		0.903	0.763	0.684
5.5–7.4	0.802	0.449	0.311		0.898	0.632	0.562
≥7.5	0.763	0.389	0.249		0.849	0.554	0.461

Abbreviations: ICC, intrahepatic cholangiocarcinoma; OS, overall survival; CSS, cancer-specific survival; LNR, lymph node ratio.

Table 3 Univariate and multivariate COX regression analyzes for OS in patients with surgically resected ICC

Variables	Univariate COX analysis			Multivariate COX analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Gender
Female	Ref			Ref
Male	1.226	1.020–1.473	0.030	1.099	0.702–1.181	0.478
Age (years)
<55	Ref			Ref
55–74	1.000	0.799–1.250	0.997	1.294	1.021–1.640	0.033
≥75	1.415	1.069–1.872	0.015	1.883	1.401–2.532	<0.001
Marriage
Married	Ref
Unmarried	0.893	0.739–1.078	0.237
T stage
T1a	Ref			Ref
T1b	1.130	0.815–1.566	0.464	1.148	0.768–1.716	0.501
T2	1.694	1.275–2.250	<0.001	1.396	1.027–1.898	0.033
T3	2.786	2.096–3.700	<0.001	2.177	1.530–3.096	<0.001
T4	3.127	2.272–4.303	<0.001	2.456	1.702–3.542	<0.001
N stage
N0	Ref			Ref
N1	2.436	1.975–3.004	<0.001	1.330	0.927–1.908	0.121
M stage
M0	Ref			Ref
M1	2.405	1.795–3.223	<0.001	1.745	1.251–2.434	0.001
LNR
<0.17	Ref			Ref
≥0.17	2.798	2.255–3.471	<0.001	1.692	1.149–2.491	0.008
Grade
Well	Ref			Ref
Moderate	1.498	1.076–2.086	0.017	1.277	0.913–1.786	0.153
Poor	2.315	1.643–3.261	<0.001	1.764	1.237–2.516	0.002
Tumor size (cm)
<3.5	Ref			Ref
3.5–5.4	1.196	0.650–1.075	0.162	1.009	0.752–1.354	0.952
5.5–7.4	1.455	1.124–1.882	0.004	1.092	0.602–3.514	0.405
≥7.5	1.512	1.180–1.937	0.001	1.099	0.626–3.652	0.359

Abbreviations: ICC, intrahepatic cholangiocarcinoma; OS, overall survival; LNR, lymph node ratio.

Table 4 Univariate and multivariate competing risk analyzes for CSS in patients with surgically resected ICC

Variables	Univariate competing risk analysis			Multivariate competing risk analysis
	SHR	95% CI	P-value	SHR	95% CI	P-value
Gender
Female	Ref
Male	1.074	0.937–1.231	0.306
Age (years)
<55	Ref
55–74	1.075	0.946–1.221	0.268
≥75	1.054	0.983–1.13	0.137
Marriage
Married	Ref
Unmarried	0.985	0.776–1.250	0.900
T stage
T1a	Ref			Ref
T1b	1.251	1.042–1.502	0.016	1.514	0.913–2.511	0.108
T2	1.384	1.098–1.744	0.006	1.690	1.078–2.651	0.022
T3	1.696	1.263–2.277	<0.001	3.414	1.936–6.021	<0.001
T4	2.635	1.620–4.287	<0.001	3.762	2.105–6.724	<0.001
N stage
N0	Ref			Ref
N1	1.802	1.431–2.270	<0.001	1.384	0.906–2.115	0.133
M stage
M0	Ref			Ref
M1	1.692	1.299–2.204	<0.001	1.296	1.138–1.475	<0.001
LNR
<0.17	Ref
≥0.17	2.065	1.435–2.971	<0.001	2.664	2.043–3.475	<0.001
Grade
Well	Ref			Ref
Moderate	1.931	1.394–2.675	<0.001	1.432	1.134–1.807	0.003
Poor	3.08	1.644–5.771	<0.001	2.134	1.532–2.972	<0.001
Tumor size (cm)
≤3.5	Ref			Ref
3.5–5.4	1.992	1.332–2.979	0.001	1.127	0.839–1.515	0.427
5.5–7.4	1.931	1.394–2.675	<0.001	1.331	0.944–1.876	0.103
≥7.5	3.08	1.644–5.771	<0.001	1.335	0.925–1.926	0.122

Abbreviations: ICC, intrahepatic cholangiocarcinoma; CSS, cancer-specific survival; LNR, lymph node ratio.

Table 5 Comparisons of c-indices between the nomograms and AJCC 8th edition TNM staging system in patients with surgically resected ICC

	Nomogram (95% CI)	AJCC 8th edition TNM staging system (95% CI)	P-value
Training cohort, OS	0.751 (0.680–0.822)	0.658 (0.607–0.709)	<0.001
Training cohort, CSS	0.736 (0.658–0.814)	0.661 (0.592–0.730)	<0.001
Validation cohort, OS	0.725 (0.666–0.784)	0.632 (0.567–0.697)	<0.001
Validation cohort, CSS	0.718 (0.669–0.767)	0.621 (0.572–0.670)	<0.001

Abbreviation: ICC, intrahepatic cholangiocarcinoma.

Figure 2 Nomograms predicting 1-, 3- and 5-year OS (A) and CSS (B) in patients with ICC after surgery. Each subtype within these variables was assigned a score on the point scale. By summing up the total score and locating it on the total point scale, we could draw a vertical line down to get the nomogram-predicted probability at each time point.

Abbreviations: CSS, cancer-specific survival; ICC, intrahepatic cholangiocarcinoma; LNR, lymph node ratio; OS, overall survival.

Figure 3 Calibration curves of the nomogram predicting OS in the development cohort: (A) 1-year OS; (B) 3-year OS; (C) 5-year OS. OS: overall survival.

Figure 4 Calibration curves of the nomogram predicting OS in the training cohort: (A) 1-year OS; (B) 3-year OS; (C) 5-year OS.

Abbreviation: OS, overall survival.

Figure 5 Calibration curves of the nomogram predicting CSS in the development cohort: (A) 1-year CSS; (B) 3-year CSS; (C) 5-year CSS.

Abbreviation: CSS, cancer-specific survival.

Figure 6 Calibration curves of the nomogram predicting CSS in the training cohort: (A) 1-year CSS; (B) 3-year CSS; (C) 5-year CSS.

Abbreviation: CSS, cancer-specific survival.

Figure 7 Decision curve analysis of nomograms and AJCC 8th edition staging system for predicting (A) 1-year OS; (B) 3-year OS; (C) 5-year OS. The grey line indicates the assumption that all patients die. The black line indicates that the assumption that all patients survive.

Abbreviation: OS, overall survival.

Figure 8 Decision curve analysis of nomograms and AJCC 8th edition staging system for predicting (A) 1-year CSS; (B) 3-year CSS; (C) 5-year CSS. The grey line indicates the assumption that all patients die. The black line indicates that the assumption that all patients survive.

Abbreviation: CSS: cancer-specific survival.

Figure S1 Kaplan–Meier cumulative OS curves in patients with ICC after surgery stratified by the clinical characteristics (A) gender; (B) age; (C) T stage; (D) N stage; (E) M stage; (F) LNR; (G) grade; (H) tumor size.

Abbreviations: OS, overall survival; ICC, intrahepatic cholangiocarcinoma; LNR, lymph node ratio.

Figure S2 Cumulative CSS in patients with ICC after surgery stratified by the clinical characteristics: (A) T stage; (B) N stage; (C) M stage; (D) LNR; (E) grade; (F) tumor size.

Abbreviations: ICC, intrahepatic cholangiocarcinoma; LNR, lymph node ratio; CSS, cancer cancer-specific survival.

Figure S3 Cumulative non-cancer specific survival in patients with ICC after surgery stratified by the clinical characteristics (A) gender; (B) age.

Table S1 Cumulative non-CSS in patients with surgically resected ICC

Variable	Non-CSS
	1-year	3-year	5-year	P-value
Total	0.921	0.793	0.737
Gender				0.004
Female	0.930	0.838	0.788
Male	0.896	0.731	0.673
Age (years)				0.019
<55	0.963	0.885	0.858
55–74	0.957	0.853	0.805
≥75	0.903	0.772	0.761
Marriage				0.302
Married	0.914	0.791	0.732
Unmarried	0.915	0.785	0.740
T stage				0.817
T1a	0.969	0.854	0.804
T1b	0.931	0.873	0.845
T2	0.968	0.828	0.787
T3	0.913	0.86	0.815
T4	0.944	0.836	0.823
N stage				0.797
N0	0.923	0.786	0.729
N1	0.877	0.801	0.762
M stage				0.445
M0	0.957	0.851	0.811
M1	0.861	0.807	0.807
LNR				0.479
LNR<0.17	0.958	0.845	0.803
LNR≥0.17	0.909	0.856	0.846
Grade				0.681
I	0.962	0.878	0.814
II	0.951	0.843	0.806
III+IV	0.949	0.845	0.827
Tumor size (cm)				0.305
≤3.5	0.965	0.742	0.709
3.5–5.4	0.931	0.742	0.709
5.5–7.4	0.904	0.816	0.749
≥7.5	0.914	0.834	0.789

Abbreviations: ICC, intrahepatic cholangiocarcinoma; CSS, cancer-specific survival; LNR, lymph node ratio.