Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
© 2024 The Korean Liver Cancer Association.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Conflicts of Interest
The authors have no conflicts of interest to disclose.
Ethics Statement
This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Samsung Medical Center (No. 2024-02-075).
Funding Statement
None.
Data Availability
The data that support the findings of this study are available from the authors upon reasonable request.
Author Contributions
Study concept and design: BGS, MSC
Data acquisition: BGS
Data analysis and interpretation: BGS
Manuscript draft: BGS
Data analysis plan and data management: BGS
Critical revision of manuscript: BGS, MJG, WK, DHS, GYG, YHP, MSC, JHL
Overall study supervision: MSC
All authors participated in the preparation of the manuscript and have seen and approved the final version.
Values are presented as mean±standard deviation, number (%), or median (range).
TACE, transarterial chemoembolization; IO, immunotherapy; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, non-B and non-C; ECOG, Eastern Cooperative Oncology Group; CTP, Child-Pugh; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein; PIVKA-II, protein induced by vitamin K antagonist-II; PV, portal vein.
Characteristic | Adjusted HR (95% CI)* | P-value |
---|---|---|
Age (years) | ||
<60 (n=95) | 1.09 (0.62-1.94) | 0.76 |
≥60 (n=70) | 1.83 (0.79-4.22) | 0.16 |
Sex | ||
Male (n=139) | 1.63 (0.97-2.73) | 0.07 |
Female (n=26) | 0.72 (0.11-4.70) | 0.74 |
ALBI grade | ||
1 (n=110) | 1.30 (0.76-2.23) | 0.33 |
2 to 3 (n=55) | 0.67 (0.28-1.59) | 0.36 |
Etiology | ||
NBNC (n=46) | 1.02 (0.35-3.00) | 0.97 |
Viral (n=119) | 1.12 (0.66-1.92) | 0.67 |
Tumor size (intrahepatic) (cm) | ||
<5 (n=36) | 5.05 (1.34-19.0) | 0.02 |
≥5 (n=129) | 1.09 (0.66-1.79) | 0.75 |
Tumor number (intrahepatic) | ||
<3 (n=63) | 0.87 (0.34-2.20) | 0.76 |
≥3 (n=102) | 1.17 (0.66-2.08) | 0.59 |
AFP (ng/mL) | ||
<400 (n=83) | 1.32 (0.65-2.65) | 0.44 |
≥400 (n=82) | 1.49 (0.76-2.92) | 0.25 |
PIVKA (ng/mL) | ||
<400 (n=50) | 1.20 (0.40-3.62) | 0.74 |
≥400 (n=115) | 1.38 (0.78-2.41) | 0.27 |
PV invasion | ||
None (n=77) | 1.58 (0.80-3.11) | 0.18 |
Segmental/lobar (n=57) | 0.89 (0.42-1.88) | 0.76 |
Main/bilateral (n=31) | 1.05 (0.30-3.62) | 0.94 |
Characteristic | Treatment group |
P-value | |||
---|---|---|---|---|---|
TACE (n=88) | Sorafenib (n=83) | Lenvatinib (n=49) | IO (n=28) | ||
Age (years) | 58.6±11.1 | 59.8±11.0 | 56.4±11.0 | 58.2±11.5 | 0.383 |
Male | 74 (84.1) | 68 (81.9) | 42 (85.7) | 23 (82.1) | 0.944 |
Etiology | 0.500 | ||||
HBV | 56 (63.6) | 51 (61.4) | 34 (69.4) | 19 (67.9) | |
HCV | 8 (9.1) | 5 (6.0) | 0 (0.0) | 2 (7.1) | |
NBNC | 24 (27.3) | 27 (32.5) | 15 (30.6) | 7 (25.0) | |
ECOG performance status | 0.477 | ||||
0 | 75 (85.2) | 71 (85.5) | 42 (85.7) | 20 (71.4) | |
1 | 12 (13.6) | 11 (13.3) | 7 (14.3) | 7 (25.0) | |
≥2 | 1 (1.1) | 1 (1.2) | 0 (0.0) | 1 (3.6) | |
CTP grade | 0.089 | ||||
A | 81 (92.0) | 68 (81.9) | 44 (89.8) | 27 (96.4) | |
B | 7 (8.0) | 15 (18.1) | 5 (10.2) | 1 (3.6) | |
ALBI grade | <0.001 | ||||
1 | 66 (75.0) | 45 (54.2) | 23 (46.9) | 21 (75.0) | |
2 | 21 (23.9) | 23 (27.7) | 15 (30.6) | 7 (25.0) | |
3 | 1 (1.1) | 15 (18.1) | 11 (22.4) | 0 (0.0) | |
AFP | 177.3 (9.8-3,592.0) | 2,618.5 (140.6-29,824.1) | 3,361.0 (87.3-39,690.0) | 484.0 (37.7-9,651.5) | 0.001 |
PIVKA-II | 1,381.0 (138.5-8,584.5) | 7,976.0 (1,332.0-28,709.0) | 6,835.0 (694.0-72,977.0) | 1,686.0 (232.0-23,459.5) | 0.001 |
Tumor number (intrahepatic) | <0.001 | ||||
1 | 36 (40.9) | 9 (11.0) | 6 (12.2) | 3 (10.7) | |
2 | 12 (13.6) | 10 (12.2) | 4 (8.2) | 2 (7.1) | |
3 | 9 (10.2) | 2 (2.4) | 2 (4.1) | 2 (7.1) | |
≥4 | 31 (35.2) | 56 (68.3) | 32 (65.3) | 20 (71.4) | |
Infiltrative | 0 (0.0) | 5 (6.1) | 5 (10.2) | 1 (3.6) | |
Tumor diameter (intrahepatic) | 6.5 (3.8-9.6) | 11.1 (7.8-13.5) | 12.4 (10.0-15.0) | 9.9 (6.8-12.1) | <0.001 |
PV invasion | <0.001 | ||||
None | 52 (59.1) | 20 (24.1) | 13 (26.5) | 12 (42.9) | |
Segmental/lobar | 28 (31.8) | 39 (47.0) | 18 (36.7) | 11 (39.3) | |
Main/contralateral | 8 (9.1) | 24 (28.9) | 18 (36.7) | 5 (17.9) | |
Bile duct invasion | 10 (11.4) | 8 (9.8) | 5 (10.2) | 3 (10.7) | 0.989 |
Nodal metastasis | 42 (47.7) | 49 (59.0) | 27 (55.1) | 18 (64.3) | 0.334 |
Distant metastasis | 0.123 | ||||
Lung metastasis | 25 (28.4) | 36 (43.4) | 18 (36.7) | 12 (42.9) | |
Bone metastasis | 21 (23.9) | 13 (15.7) | 6 (12.2) | 2 (7.1) |
Characteristic | Univariable |
Multivariable |
||
---|---|---|---|---|
HR (95% CI) | P-value | HR (95% CI) | P-value | |
Age (years) | 0.99 (0.98-1.01) | 0.248 | ||
Male | 0.83 (0.57-1.21) | 0.325 | ||
ECOG PS ≥1 (vs. 0) | 1.03 (0.71-1.51) | 0.878 | ||
ALBI grade | ||||
1 | 1 (reference) | 1 (reference) | ||
2 | 1.33 (0.96-1.83) | 0.089 | 1.28 (0.90-1.82) | 0.163 |
3 | 2.43 (1.56-3.77) | <0.001 | 2.01 (1.25-3.25) | 0.004 |
Etiology, viral (vs. non-viral) | 0.92 (0.68-1.25) | 0.596 | ||
Log (AFP) | 1.07 (1.03-1.11) | <0.001 | ||
Log (PIVKA-II) | 1.12 (1.06-1.18) | <0.001 | 1.06 (1.00-1.13) | 0.045 |
Tumor number (intrahepatic) ≥3 | 1.36 (1.01-1.85) | 0.045 | ||
Tumor size (intrahepatic) ≥5 cm | 1.93 (1.31-2.84) | <0.001 | ||
PV invasion | ||||
None | 1 (reference) | 1 (reference) | ||
Segmental/lobar | 2.03 (1.46-2.81) | <0.001 | 1.76 (1.24-2.49) | 0.001 |
Main/contralateral | 2.46 (1.68-3.61) | <0.001 | 1.91 (1.25-2.91) | 0.003 |
Lymph node metastasis | 1.33 (1.00-1.77) | 0.048 | ||
Lung metastasis | 1.19 (0.89-1.59) | 0.244 | ||
Bone metastasis | 0.90 (0.63-1.30) | 0.579 | ||
Treatment | ||||
TACE | 1 (reference) | 1 (reference) | ||
Sorafenib | 2.53 (1.79-3.57) | <0.001 | 1.97 (1.36-2.85) | <0.001 |
Lenvatinib | 1.98 (1.33-2.95) | <0.001 | 1.21 (0.77-1.90) | 0.411 |
IO | 1.18 (0.72-1.93) | 0.521 | 1.01 (0.61-1.67) | 0.973 |
Characteristic | Adjusted HR (95% CI) |
P-value |
---|---|---|
Age (years) | ||
<60 (n=95) | 1.09 (0.62-1.94) | 0.76 |
≥60 (n=70) | 1.83 (0.79-4.22) | 0.16 |
Sex | ||
Male (n=139) | 1.63 (0.97-2.73) | 0.07 |
Female (n=26) | 0.72 (0.11-4.70) | 0.74 |
ALBI grade | ||
1 (n=110) | 1.30 (0.76-2.23) | 0.33 |
2 to 3 (n=55) | 0.67 (0.28-1.59) | 0.36 |
Etiology | ||
NBNC (n=46) | 1.02 (0.35-3.00) | 0.97 |
Viral (n=119) | 1.12 (0.66-1.92) | 0.67 |
Tumor size (intrahepatic) (cm) | ||
<5 (n=36) | 5.05 (1.34-19.0) | 0.02 |
≥5 (n=129) | 1.09 (0.66-1.79) | 0.75 |
Tumor number (intrahepatic) | ||
<3 (n=63) | 0.87 (0.34-2.20) | 0.76 |
≥3 (n=102) | 1.17 (0.66-2.08) | 0.59 |
AFP (ng/mL) | ||
<400 (n=83) | 1.32 (0.65-2.65) | 0.44 |
≥400 (n=82) | 1.49 (0.76-2.92) | 0.25 |
PIVKA (ng/mL) | ||
<400 (n=50) | 1.20 (0.40-3.62) | 0.74 |
≥400 (n=115) | 1.38 (0.78-2.41) | 0.27 |
PV invasion | ||
None (n=77) | 1.58 (0.80-3.11) | 0.18 |
Segmental/lobar (n=57) | 0.89 (0.42-1.88) | 0.76 |
Main/bilateral (n=31) | 1.05 (0.30-3.62) | 0.94 |
Values are presented as mean±standard deviation, number (%), or median (range). TACE, transarterial chemoembolization; IO, immunotherapy; HBV, hepatitis B virus; HCV, hepatitis C virus; NBNC, non-B and non-C; ECOG, Eastern Cooperative Oncology Group; CTP, Child-Pugh; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein; PIVKA-II, protein induced by vitamin K antagonist-II; PV, portal vein.
HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; PS, performance status; ALBI, albumin-bilirubin; AFP, alphafetoprotein; PIVKA-II, protein induced by vitamin K antagonist-II; PV, portal vein; TACE, transarterial chemoembolization; IO, immunotherapy.
HR, hazard ratio; CI, confidence interval; ALBI, albumin-bilirubin; NBNC, non-B and non-C; AFP, alpha-fetoprotein; PIVKA, protein induced by vitamin K antagonist; PV, portal vein. Adjusted for age, sex, ALBI grade, etiology, AFP, PIVKA, size, number, PV invasion except for grouping variables.