Nomogram for Predicting the Prognosis of Patients with Hepatocellular Carcinoma Presenting with Pulmonary Metastasis

Figures & data

Table 1 Multivariable Logistic Regression Analysis of Characteristics of Patients with Hepatocellular Carcinoma Presenting with Pulmonary Metastasis at the Initial Diagnosis (%)

Characteristics	Total	HCC Patients (2010–2015)		OR (95% CI)	P value
		With PM	Without PM
Patients	25,236	897 (3.6)	24,339 (96.4)	–	–
Age
<50	1388	81 (5.8)	1307 (94.6)	1(Reference)	1
50–60	7346	277 (3.1)	7069 (96.9)	0.73(0.56–0.98)	0.03^✱
60–70	9281	285 (3.1)	8996 (96.9)	0.62(0.47–0.82)	<0.001^✱
70–80	4917	169 (3.4)	4748 (96.6)	0.75(0.56–1.02)	0.06
>80	2304	85 (3.7)	2219 (96.3)	0.85(0.60–1.19)	0.34
Race
White	17,327	534 (3.1)	16,793 (96.9)	1(Reference)	1
Black	3508	168 (4.8)	3340 (95.2)	1.36(1.12–1.64)	0.002^✱
Other^✱✱	4401	195 (4.4)	4206 (95.6)	1.45(1.21–1.74)	<0.001^✱
Sex
Female	5934	192 (3.2)	5742 (96.8)	1(Reference)	1
Male	19,302	705 (3.7)	18,597(96.3)	1.01(0.84–1.20)	0.951
Edmonson-Steiner classification
Unknown	16,406	583(3.6)	15,823(96.5)	1(Reference)	1
I	2736	57(2.1)	2679(97.9)	0.73(0.54–0.96)	0.03^✱
II	4168	127 (3.0)	4041 (97.0)	0.95(0.77–1.56)	0.60
III	1800	120 (6.7)	1680 (93.3)	1.43(1.14–1.76)	0.001^✱
IV	126	10 (7.9)	116 (92.1)	1.78(0.84–3.36)	0.10
T stage
T1	12,259	236 (1.9)	12,023 (98.1)	1(Reference)	1
T2	5997	114 (1.9)	5883 (98.1)	0.90(0.71–1.13)	0.39
T3	6154	408 (6.6)	5746 (93.4)	2.41(2.02–2.87)	<0.001^✱
T4	826	139 (16.8)	687 (83.2)	5.96(4.67–7.58)	<0.001^✱
N stage
N0	23,504	679 (2.9)	22,825 (97.1)	1(Reference)	1
N1	1732	218 (12.6)	1514 (87.4)	2.38(1.98–2.85)	<0.001^✱
Bone metastasis
None	24,499	754 (3.1)	23,745 (96.9)	1(Reference)	1
Yes	737	143 (19.4)	594 (80.6)	4.40(3.47–5.55)	<0.001^✱
Brain metastasis
None	25,183	879 (3.5)	24,304 (96.5)	1(Reference)	1
Yes	53	18 (34.0)	35 (66.0)	6.75(3.48–12.63)	<0.001^✱
Intrahepatic metastasis
None	25,045	821 (3.3)	24,224 (96.7)	1(Reference)	1
Yes	191	76 (39.8)	115 (60.2)	6.94(3.48–12.63)	<0.001^✱
AFP
Unknown	4038	121 (3.0)	3917 (97.0)	1(Reference)	1
Elevated	15,244	680 (4.5)	14,564 (95.5)	1.05(0.85–1.30)	0.64
Normal	5954	96 (1.6)	5858 (98.4)	0.56(0.42–0.74)	<0.001^✱
Insurance status
Uninsured	11,027	367 (3.3)	10,660 (96.7)	1(Reference)	1
Insured	14,209	530 (3.7)	13,679 (96.3)	0.94(0.81–1.10)	0.42
Marital status
Unmarried	11,021	401 (3.6)	10,620 (96.4)	1(Reference)	1
Married	14,215	496 (3.5)	13,719 (96.5)	0.88(0.76–1.02)	0.09

Notes: ^✱Indicates significance of P<0.05. ^✱✱Indicates American Indian/AK Native, Asian/Pacific Islander, and unknown.

Abbreviations: HCC, hepatocellular carcinoma; PM, pulmonary metastasis; AFP, alpha fetoprotein; OR, odds ratio; CI, confidence interval.

Table 2 Comparison of Characteristics of the Primary and Validation Sets (%)

Characteristics	All Patients	Primary Set	Validation Set	P value
Patients	897	598	299
Age				0.824
<50	81(9.0)	54 (9.0)	27 (9.0)
50–60	277(30.9)	192 (32.1)	85 (28.4)
60–70	285(31.8)	186 (31.1)	99 (33.1)
70–80	169(18.8)	112 (18.8)	57(19.1)
>80	85(9.5)	54 (9.0)	31,910.4)
Race				0.389
White	534(59.5)	362 (60.5)	172 (57.5)
Black	168(18.7)	114 (19.1)	54(18.1)
Other^✱✱	195(21.7)	122 (20.4)	73 (24.4)
Sex				0.730
Female	192(21.4)	126 (21.1)	66 (22.1)
Male	705(78.6)	472 (78.9)	233 (77.9)
Edmonson-Steiner classification				0.921
Unknown	583(65.0)	387 (64.7)	196 (65.6)
I	57(6.4)	38 (6.4)	19 (6.4)
II	127(14.2)	82 (13.7)	45 (15.1)
III	120(13.4)	84(14)	36(12.0)
IV	10(1.1)	7(1.2)	3(1.0)
T stage				0.889
T1	236(26.3)	156(26.1)	80(26.8)
T2	114(12.7)	79(13.2)	35(11.7)
T3	408(45.5)	273(45.7)	135(45.2)
T4	139(15.5)	90 (15.1)	49(16.4)
N stage				0.660
N0	679(75.7)	450 (75.3)	229(76.6)
N1	218(24.3)	148 (24.7)	70(23.4)
Bone metastasis				0.949
None	754(84.1)	503 (84.1)	251(83.9)
Yes	143(15.9)	95 (15.9)	48(16.1)
Brain metastasis				1
None	879(98.0)	586 (98.0)	293(98.0)
Yes	18(0.2)	12 (0.02)	6(0.02)
Intrahepatic metastasis				0.397
None	821(91.5)	544 (91.0)	277(92.6)
Yes	76(8.5)	54 (9.0)	22(7.4)
AFP				0.219
Unknown	121(13.5)	89 (14.9)	32(10.7)
Elevated	680(75.8)	447 (74.7)	233(77.9)
Normal	96(10.7)	62 (10.4)	34(11.4)
Insurance status				0.962
Uninsured	367(40.9)	245 (41.0)	122(40.8)
Insured	530(59.1)	353 (59.0)	177(59.2)
Marital status				0.129
Unmarried	401(44.7)	278 (46.5)	123(41.1)
Married	496(55.3)	320 (53.5)	176(58.9)

Note: ^✱✱Indicates American Indian/AK Native, Asian/Pacific Islander, and unknown.

Abbreviation: AFP, alpha fetoprotein.

Table 3 Univariate and Multivariate Analysis of Overall Survival for the Primary Set

Characteristics	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Age
<50	1(Reference)	1	1(Reference)	1
50–60	1.11(0.86–1.44)	0.410	1.26(0.96–1.64)	0.091
60–70	1.13(0.88–1.47)	0.333	1.19(0.91–1.55)	0.204
70–80	1.14(0.87–1.50)	0.342	1.28(0.96–1.71)	0.088
>80	1.07(0.77–1.47)	0.677	1.14(0.82–1.59)	0.425
Race
White	1(Reference)	1	1(Reference)	1
Black	1.03(0.86–1.23)	0.747	0.98(0.82–1.18)	0.871
Other^✱✱	1.04(0.87–1.23)	0.685	1.17(0.97–1.39)	0.929
Sex
Female	1(Reference)	1	1(Reference)	1
Male	1.32(1,17–1.41)	0.038^✱	1.21(1.01–1.43)	0.036^✱
Edmonson-Steiner classification
Unknown	1(Reference)	1	1(Reference)	1
I	0.74(0.56–0.99)	0.040^✱	0.89(0.67–1.18)	0.415
II	0.82(0.67–1.00)	0.055	0.97(0.79–1.18)	0.747
III	1.07(0.87–1.32)	0.488	1.17(0.95–1.44)	0.140
IV	1.22(0.65–2.29)	0.529	1.82(0.95–3.50)	0.069
T stage
T1	1(Reference)	1	1(Reference)	1
T2	1.39(1.10–1.75)	0.006^✱	1.32(1.04–1.68)	0.023^✱
T3	1.40(1.19–1.66)	<0.001^✱	1.42(1.19–1.70)	<0.001^✱
T4	1.40(1.13–1.75)	0.002^✱	1.47(1.17–1.84)	<0.001^✱
N stage
N0	1(Reference)	1	1(Reference)	1
N1	1.24(1.06–1.46)	0.006^✱	1.07(0.90–1.26)	0.437
Bone metastasis
None	1(Reference)	1	1(Reference)	1
Yes	1.20(1.00–1.44)	0.045^✱	1.29(1.04–1.60)	0.022^✱
Brain metastasis
None	1(Reference)	1	1(Reference)	1
Yes	1.20(0.75–1.91)	0.455	1.15(0.70–1.87)	0.580
Intrahepatic metastasis
None	1(Reference)	1	1(Reference)	1
Yes	1.08(0.85–1.38)	0.543	0.96(0.75–1.23)	0.752
AFP
Unknown	1(Reference)	1	1(Reference)	1
Elevated	0.99(0.82–1.22)	0.969	1.00(0.81–1.25)	0.965
Normal	0.73(0.55–0.97)	0.027^✱	0.75(0.56–0.83)	0.032^✱
Insurance status
Uninsured	1(Reference)	1	1(Reference)	1
Insured	1.03(0.90–1.18)	0.693	1.10(0.94–1.28)	0.217
Marital status
Unmarried	1(Reference)	1	1(Reference)	1
Married	0.86(0.75–0.99)	0.036^✱	0.94(0.81–1.10)	0.449
Treatment
No surgery	1(Reference)	1	1(Reference)	1
Local tumor destruction	0.29(0.16–0.53)	<0.001^✱	0.32(0.17–0.59)	<0.001^✱
Hepatectomy	0.36(0.20–0.66)	<0.001^✱	0.34(0.18–0.63)	<0.001^✱
Radiation
None	1(Reference)	1	1(Reference)	1
Yes	0.80(0.65–0.98)	0.032^✱	0.67(0.53–0.86)	0.001^✱
Chemotherapy
None	1(Reference)	1	1(Reference)	1
Yes	0.60(0.53–0.69)	<0.001^✱	0.56(0.48–0.65)	<0.001^✱

Notes: ^✱Indicates significance of P<0.05. ^✱✱Indicates American Indian/AK Native, Asian/Pacific Islander, and unknown.

Abbreviations: AFP, alpha fetoprotein; HR, hazard ratio; CI, confidence interval.

Figure 1 Nomogram for predicting the overall survival of patients with hepatocellular carcinoma (HCC) presenting with pulmonary metastasis.

Figure 2 Calibration curves for the nomograms. The nomograms predicted the 1- (A for the primary cohort, B for the validation cohort), 2-year (C for the primary cohort, D for the validation cohort) and 3-year (E for the primary cohort, F for the validation cohort) overall survival of patients with hepatocellular carcinoma (HCC) presenting with pulmonary metastasis.