Concomitant lung metastasis in patients with advanced hepatocellular carcinoma

Table 1 Baseline characteristics of hepatocellular carcinoma patients presenting with lung metastasis (mean ± SD) n (%)

	Total (n = 76)	Untreated group (n = 22)	Single treated group (n = 19)	Combined treated group (n = 35)	P value
Sex
Male	59 (77.6)	16 (72.7)	15 (78.9)	28 (80.0)	0.804
Female	17 (22.4)	6 (27.3)	4 (21.1)	7 (20.0)
Age (yr)	52.4 ± 10.7	52.8 ± 9.3	52.5 ± 11.6	52.1 ± 11.4	0.971
Etiology
HBV	63 (82.9)	18 (82.9)	16 (84.2)	29 (82.9)	0.989
HCV	3 (3.9)	1 (4.5)	1 (5.3)	1 (2.9)
Alcohol	5 (6.6)	1 (4.5)	1 (5.3)	3 (8.6)
Non-B and non-C	5 (6.6)	2 (9.1)	1 (5.3)	2 (5.7)
Cirrhosis	65 (85.5)	20 (90.9)	17 (89.5)	28 (80.0)	0.443
Platelet (-3)	185.8 ± 75.5	180.9 ± 95.1	174.3 ± 74.0	195.1 ± 62.6	0.593
Albumin (g/L)	36.5 ± 4.3	36.3 ± 5.4	35.3 ± 3.5	37.3 ± 3.7	0.276
ALT (IU/L), median (range)	35 (10-352)	35 (15-352)	37 (15-124)	34 (10-210)	0.456
AST (IU/L), median (range)	35 (16-453)	41 (16-453)	44 (20-173)	33 (17-223)	0.364
Total bilirubin (μmol/L)	23.7 ± 13.3	28.1 ± 17.4	23.3 ± 8.1	21.2 ± 12.2	0.162
Prothrombin time (s)	12.9 ± 1.7	13.3 ± 2.3	13.0 ± 1.3	12.5 ± 1.3	0.241
AFP (ng/mL)
< 400	36 (47.4)	10 (45.5)	7 (36.8)	19 (54.3)	0.461
≥ 400	40 (52.6)	12 (54.5)	12 (63.2)	16 (52.6)
ECOG score
0	17 (22.4)	4 (18.2)	4 (21.1)	9 (25.7)	0.672
1	54 (71.1)	16 (72.7)	15 (78.9)	23 (65.7)
2	5 (6.6)	2 (9.1)	0 (0)	3 (8.6)
Ascites
None	67 (88.2)	18 (81.8)	16 (84.2)	33 (94.3)	0.303
Mild–moderate	9 (11.8)	4 (18.2)	3 (15.8)	2 (5.7)
Child-Pugh score
A	61 (80.3)	16 (72.7)	14 (73.7)	31 (88.6)	0.243
B	15 (19.7)	6 (27.3)	5 (26.3)	4 (11.4)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; ALT: Alanine transaminase; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein; ECOG: Eastern cooperative oncology group.

Table 2 Characteristics of intrahepatic tumor and lung metastasis of hepatocellular carcinoma patients presenting with lung metastasis (mean ± SD) n (%)

	Total (n = 76)	Untreated group (n = 22)	Single treated group (n = 19)	Combined treated group (n = 35)	P value
Intrahepatic tumor
Maximum tumor diameter (cm)	9.3 ± 3.0	10.7 ± 3.2	9.7 ± 2.8	8.2 ± 2.5	0.007
Tumor number
Solitary	29 (38.2)	9 (40.9)	6 (31.6)	14 (40.0)	0.791
Multiple/diffuse	47 (61.8)	13 (59.1)	13 (68.4)	21 (60.0)
Tumor location
Right	39 (51.3)	13 (59.1)	8 (42.1)	18 (51.4)	0.834
Left	15 (19.7)	4 (18.2)	4 (21.1)	7 (20.0)
Both	22 (28.9)	5 (22.7)	7 (36.8)	10 (28.6)
Portal vein tumor thrombus
Absence	54 (71.1)	14 (63.6)	12 (63.2)	28 (80.0)	0.283
Presence	22 (28.9)	8 (36.4)	7 (36.8)	7 (20.0)
Hepatic vein tumor thrombus
Absence	67 (88.2)	19 (86.4)	15 (78.9)	33 (94.2)	0.238
Presence	9 (11.8)	3 (13.6)	4 (21.1)	2 (5.7)
Lung metastasis
Number of metastasis
Solitary	17 (22.4)	4 (18.2)	3 (15.8)	10 (28.6)	0.479
Multiple	59 (77.6)	18 (81.8)	16 (84.2)	25 (71.4)
Location of metastasis
Right lung lobe	28 (36.8)	6 (27.3)	8 (42.1)	14 (40.0)	0.721
Left lung lobe	13 (17.1)	4 (18.2)	2 (10.5)	7 (20.0)
Bialteral lung lobes	35 (46.1)	12 (54.5)	9 (47.4)	14 (40.0)
Maximum metastasis diameter (cm)	2.5 ± 0.9	2.6 ± 0.9	2.2 ± 1.2	2.5 ± 0.8	0.445

Table 3 Treatment modalities for intrahepatic tumor and/or metastatic lung nodule(s)

Treatment modalities	n (%)
Single treatment modality in treated patients (n = 19)
Hepatectomy	4 (21.1)
Pulmonary metastasectomy	0 (0)
Transcatheter arterial chemoembolization	6 (31.6)
Radiotherapy	5 (26.3)
Oral sorafenib	4 (21.1)
Combined treatment modalities in treated patients (n = 35)
Hepatectomy + pulmonary metastasectomy	3 (8.6)
Hepatectomy + pulmonary metastasectomy + oral sorafenib	1 (2.9)
Hepatectomy + transcatheter arterial chemoembolization + radiotherapy	6 (17.1)
Hepatectomy + radiotherapy	9 (25.7)
Hepatectomy + transcatheter arterial chemoembolization + radiotherapy + oral sorafenib	2 (5.7)
Hepatectomy + radiotherapy + oral sorafenib	2 (5.7)
Transcatheter arterial chemoembolization + radiotherapy	6 (17.1)
Transcatheter arterial chemoembolization + radiotherapy + oral sorafenib	3 (8.6)
Transcatheter arterial chemoembolization + oral sorafenib	1 (2.9)
Radiotherapy + oral sorafenib	2 (5.7)

Table 4 Univariate and multivariate analyses to identify prognostic factors of overall survival for hepatocellular carcinoma patients presenting with lung metastasis

Variables	P value
	Univariate analysis	Multivariate analysis
Sex
Male/female	0.988	–
Age (yr)
< 50/≥ 50	0.423	–
Etiology
Non-hepatitis/hepatitis	0.111	–
Cirrhosis
Absence/presence	0.36	–
ECOG score
2000/1/2	0.012	0.3
Child-Pugh score
A/B	< 0.001	< 0.001
Ascites
No/yes	0.031	0.879
Platelet (-3)
< 100/≥ 100	0.198	–
Albumin (g/L)
< 37.7/≥ 37.7	0.134	–
ALT (IU/L)
< 40/≥ 40	0.734	–
AST (IU/L)
< 40/≥ 40	0.356	–
Total bilirubin (μmol/L)
< 17.1/≥ 17.1	0.319	–
Prothrombin time (s)
< 14.0/≥ 14.0	0.251	–
AFP (ng/mL)
< 400/≥ 400	0.03	0.384
Maximum intrahepatic tumor diameter (cm)
< 8.0/≥ 8.0	0.039	0.214
Intrahepatic tumor number
Solitary/multiple or diffuse	0.279	–
Intrahepatic tumor location
Single lobe/both lobes	0.435	–
Portal vein tumor thrombus
No/yes	< 0.001	< 0.001
Hepatic vein tumor thrombus
No/yes	0.031	0.194
Lung metastatic tumor number
Solitary/multiple	0.018	0.321
Lung metastatic tumor location
Single lobe/both lobes	0.156	–
Maximum metastasis diameter (cm)
< 2.5/≥ 2.5	0.129	–
Treatment modality
No/yes	< 0.001	< 0.001

The cutoffs of continuous variable were set according to median value. ECOG: Eastern cooperative oncology group; ALT: Alanine transaminase; AST: Aspartate aminotransferase; AFP: α-fetoprotein.