Abstract
Background/Aims
Methods
Results
ACKNOWLEDGMENTS
Supplementary Information
Notes
AUTHORSHIP STATEMENT
1) Jeong-Hoon Lee and Young Eun Chon take responsibility for the integrity of the work as a whole, from inception to published article.
2) Specific author contributions: Conception: Young Eun Chon, Han Ah Lee, Jun Sik Yoon and Jeong-Hoon Lee; study design: Young Eun Chon, Han Ah Lee, Jun Sik Yoon and Jeong-Hoon Lee; participation in patient management and data collection: Jun Sik Yoon, Han Ah Lee, Jun Yong Park, Bo Hyun Kim, In Joon Lee, Suk Kyun Hong, Dong Hyeon Lee, Hyun-Joo Kong, Young-Joo Won, Eunyang Kim, Young Eun Chon, and Jeong-Hoon Lee; contribution to the data acquisition, responsibility for writing the paper, and statistical analysis: Young Eun Chon, Han Ah Lee, Jun Sik Yoon, and Jeong-Hoon Lee.
3) All authors have reviewed the paper and approved the final version.
REFERENCES
Table 1
Variable | 2012–2014 | 2008–2011 | P-value |
---|---|---|---|
Demographic variable | |||
Age (years) | 60.0 (53.0–76.0) | 59.0 (51.0–68.0) | <0.001 |
Sex (male) | 3,638 (79.6) | 4,790 (78.7) | 0.310 |
Diabetes | 1,197 (26.4) | 1,401 (23.0) | 0.001 |
Hypertension | 1,648 (36.4) | 1,808 (29.7) | <0.001 |
Body mass index (kg/m2) | 23.7 (21.5–25.9) | 23.7 (21.7–25.8) | 0.800 |
Smoking | 2,069 (45.7) | 2,657 (43.7) | 0.240 |
Etiology | (n=4,572, missing=0) | (n=5,291, missing=792) | <0.001 |
HBV† | 2,700 (59.1) | 3,810 (72.0) | |
HCV | 490 (10.7) | 636 (12.0) | |
Alcohol | 616 (13.5) | 711 (13.4) | |
Others | 766 (16.8) | 134 (2.5) | |
Performance status* | (n=3,114, missing=1,458) | (n=4,162, missing=1,921) | <0.001 |
0 | 2,224 (71.4) | 3,231 (77.6) | |
1 | 665 (21.4) | 641 (15.4) | |
2 | 141 (4.5) | 159 (3.8) | |
3 | 62 (2.0) | 74 (1.8) | |
4 | 22 (0.7) | 57 (1.4) | |
Ascites | (n=4,566, missing=6) | (n=6,006, missing=77) | 0.610 |
Absent | 3,462 (75.8) | 4,509 (75.1) | |
Mild | 701 (15.4) | 964 (16.1) | |
Moderate to severe | 403 (8.8) | 533 (8.9) | |
Encephalopathy | (n=4,567, missing=5) | (n=6,045, missing=38) | 0.270 |
None | 4,468 (97.8) | 5,894 (97.5) | |
Mild to moderate (grade 1 or 2) | 84 (1.8) | 119 (2.0) | |
Severe (grade 3 or 4) | 15 (0.3) | 32 (0.5) | |
|
|||
Laboratory variable | |||
Total bilirubin (mg/dL) | 0.9 (0.6–1.5) | 1.0 (0.70–1.60) | <0.001 |
Serum albumin (g/dL) | 3.8 (3.3–4.3) | 3.8 (3.2–4.2) | <0.001 |
Alanine aminotransferase (IU/L) | 35.0 (23.0–57.5) | 38.0 (24.0–61.0) | <0.001 |
Platelet count (109/L) | 144.0 (100.0–196.0) | 139.0 (95.0–199.0) | 0.151 |
Prothrombin time (INR) | 1.10 (1.03–1.21) | 1.11 (1.04–1.22) | 0.020 |
Creatinine (mg/dL) | 0.88 (0.73–1.02) | 0.90 (0.74–1.00) | 0.305 |
Sodium (mmol/L) | 139.0 (136.0–141.0) | 139.0 (136.0–141.0) | 0.482 |
Glucose (mg/dL) | 110.0 (95.0–142.0) | 109.0 (94.0–139.0) | 0.200 |
Total cholesterol (mg/dL) | 156.0 (131.0–183.0) | 155.0 (130.0–182.0) | 0.252 |
Child-Turcotte-Pugh class | (n=4,425, missing=147) | (n=5,719, missing=364) | <0.001 |
A | 3,226 (72.9) | 4,063 (71.0) | |
B | 991 (22.4) | 1,362 (23.8) | |
C | 208 (4.7) | 294 (5.1) | |
MELD score | 8.0 (7.0–1.0) | 8.6 (7.3–11.1) | <0.001 |
MELD-Na score | 10.0 (8.0–13.0) | 10.1 (8.0–13.8) | 0.003 |
|
|||
Tumor variable | |||
Alpha-fetoprotein (ng/mL) | 30.7 (5.8–679.7) | 47.4 (7.3–785.0) | <0.001 |
PIVKA-II (mAU/mL) | 125.0 (27.0–2,228.0) | 144.5 (30.0–1,373.0) | 0.008 |
Numbers of tumors | (n=4,552, missing=20) | (n=6,161, missing=22) | 0.624 |
1 | 2,729 (60.0) | 3,725 (61.5) | |
2 | 646 (14.2) | 826 (13.6) | |
3 | 186 (4.1) | 247 (4.1) | |
4 | 74 (1.6) | 95 (1.6) | |
≥5 | 917 (20.1) | 1,168 (19.3) | |
Maximum tumor diameter (cm) | 3.4 (2.0–6.8) | 3.0 (2.0–5.4) | <0.001 |
Portal vein invasion | 1,061 (23.3) | 1,477 (24.3) | 0.242 |
Hepatic vein invasion | 261 (5.7) | 339 (5.6) | 0.498 |
Bile duct invasion | 100 (2.2) | 159 (2.6) | 0.191 |
Lymph node metastasis | 331 (7.3) | 431 (7.1) | 0.492 |
Distant metastasis | 460 (10.1) | 602 (9.9) | 0.490 |
Modified UICC Stage | (n=4,534, missing=38) | (n=6,045, missing=38) | 0.643 |
Stage I | 685 (15.0) | 854 (14.1) | |
Stage II | 1,674 (36.6) | 2,267 (37.5) | |
Stage III | 1,174 (25.7) | 1,577 (26.1) | |
Stage IV-A | 541 (11.8) | 746 (12.3) | |
Stage IV-B | 460 (10.1) | 601 (9.9) | |
BCLC stage | (n=3,727, missing=845) | (n=5,697, missing=386) | <0.001 |
0 | 145 (3.9) | 489 (8.6) | |
A | 1,376 (36.9) | 2,260 (39.7) | |
B | 465 (12.5) | 658 (11.5) | |
C | 1,470 (39.4) | 1,923 (33.8) | |
D | 271 (7.3) | 391 (6.9) |
HBV, hepatitis B virus; HCV, hepatitis C virus; INR, international normalized ratio; MELD, Model for End stage Liver Disease; PIVKA-II, protein induced by vitamin K absence-II; UICC, Union for International Cancer Control; BCLC, Barcelona Clinic Liver Cancer.
Table 2
Treatment modality | 2012–2014 | 2008–2011 |
---|---|---|
Surgical resection | 890 (19.8) | 998 (16.7) |
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Liver transplantation | 51 (1.1) | 55 (0.9) |
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Local ablation therapy | 476 (10.6) | 636 (10.6) |
RFA | 440 | 594 |
PEI | 35 | 37 |
Other local ablation | 1 | 5 |
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Transarterial therapy | 1,685 (37.5) | 2,493 (41.7) |
Conventional TACE | 1,527 | 2,407 |
TACE with drug-eluting beads | 99 | 64 |
Radioembolization | 21 | 7 |
HAIC | 38 | 82 |
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Combination therapy* | 113 (2.5) | 108 (1.8) |
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Systemic therapy | 228 (5.1) | 224 (3.7) |
Sorafenib | 205 | 175 |
Other systemic agents | 23 | 77 |
|
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External beam radiation therapy | 66 (1.5) | 61 (1.0) |
|
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Best supportive care | 857 (19.1) | 1,295 (21.7) |
|
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Miscellaneous therapies† | 130 (2.9) | 104 (1.7) |
Table 3
Variable | Value | Median OS (years, 95% CI) | Year | ||||
---|---|---|---|---|---|---|---|
|
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1 | 2 | 3 | 4 | 5 | |||
All patients | 4,572 (100) | 2.90 (2.64–3.11) | 67.7 | 56.6 | 49.3 | 44.6 | 41.9 |
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Age (years; n=4,572, missing values=0) | |||||||
<40 | 136 (3.0) | 2.70 (1.26–5.48) | 61.8 | 53.7 | 47.1 | 44.1 | 42.3 |
40–49 | 557 (12.2) | 2.99 (2.27–4.25) | 65.2 | 56 | 49.9 | 46.1 | 43.9 |
50–59 | 1,486 (32.5) | 4.18 (3.50–5.94) | 69.9 | 61 | 54.8 | 50.8 | 48 |
60–69 | 1,209 (26.4) | 4.19 (3.54–5.37) | 72.9 | 62.5 | 54.7 | 50.7 | 47.7 |
≥70 | 1,184 (25.9) | 1.65 (1.50–1.87) | 61.7 | 45.8 | 37 | 29.8 | 27.4 |
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Sex (n=4,572, missing values=0) | |||||||
Male | 3,638 (79.6) | 2.67 (2.43–2.92) | 66.6 | 55.2 | 47.7 | 43.3 | 40.5 |
Female | 934 (20.4) | 3.92 (3.22–5.47) | 72.1 | 62.2 | 55.6 | 49.6 | 47.3 |
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Etiology (n=4,572, missing values=0) | |||||||
HBV* | 2,700 (59.1) | 3.64 (3.12–4.34) | 68.2 | 58.9 | 52.4 | 49.0 | 46.5 |
HCV | 490 (10.7) | 2.56 (2.15–3.06) | 72.4 | 55.7 | 46.7 | 38.0 | 34.5 |
Alcohol | 616 (13.5) | 2.46 (2.04–2.88) | 68.0 | 54.5 | 45.0 | 39.4 | 36.4 |
Others | 766 (16.8) | 2.04 (1.68–2.44) | 62.1 | 50.3 | 43.0 | 37.1 | 35.0 |
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Child-Turcotte-Pugh classification (n=4,425, missing values=147) | |||||||
A | 3,226 (72.9) | NR (5.24-NR) | 79.7 | 68.4 | 60.6 | 55.5 | 52.1 |
B | 991 (22.4) | 0.57 (0.49–0.68) | 39.1 | 27.9 | 21.6 | 17.6 | 16.6 |
C | 208 (4.7) | 0.25 (0.20–0.33) | 26.4 | 19.2 | 13.9 | 12.5 | 11.1 |
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Alpha-fetoprotein (ng/mL; n=4,197, missing values=375) | |||||||
<11.45 | 1,599 (38.1) | NR (NR-NR) | 85.2 | 74.5 | 66.4 | 61.3 | 58.2 |
11.45–19.99 | 314 (7.5) | 4.36 (3.61–5.15) | 77.1 | 66.6 | 59.6 | 52.2 | 46.4 |
20.00–99.99 | 653 (15.6) | 3.48 (2.99–4.31) | 75.0 | 62.6 | 53.4 | 47.6 | 44.6 |
100.00–199.99 | 217 (5.2) | 3.24 (2.28–4.77) | 71.4 | 60.4 | 52.5 | 45.2 | 42.2 |
200.00–399.99 | 226 (5.4) | 2.17 (1.34–2.68) | 62.4 | 51.8 | 42.0 | 36.7 | 33.7 |
≥400.00 | 1,188 (28.3) | 0.61 (0.55–0.68) | 39.0 | 28.3 | 23.7 | 21.5 | 20.4 |
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Modified UICC stage (n=4,534, missing values=38) | |||||||
Stage I | 685 (15.0) | NR (NR-NR) | 93.9 | 87.9 | 81.8 | 76.6 | 74.0 |
Stage II | 1,674 (36.6) | NR (NR-NR) | 87.0 | 76.9 | 68.7 | 62.7 | 59.1 |
Stage III | 1,174 (25.7) | 1.85 (1.63–2.07) | 64.4 | 48.0 | 37.9 | 32.7 | 29.5 |
Stage IV-A | 541 (11.8) | 0.44 (0.39–0.50) | 29.8 | 16.6 | 13.1 | 10.7 | 9.3 |
Stage IV-B | 460 (10.1) | 0.27 (0.25–0.31) | 13.5 | 6.1 | 3.7 | 2.0 | 2.0 |
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BCLC stage (n=3,727, missing values=845) | |||||||
0 | 145 (3.9) | NR (NR-NR) | 97.2 | 93.8 | 91.0 | 86.2 | 83.4 |
A | 1,376 (36.9) | NR (NR-NR) | 92.7 | 83.6 | 76.3 | 71.0 | 66.8 |
B | 465 (12.5) | 2.81 (2.39–3.29) | 75.7 | 59.8 | 48.4 | 40.9 | 36.7 |
C | 1,470 (39.4) | 0.75 (0.67–0.87) | 44.6 | 31.6 | 24.9 | 21.3 | 19.7 |
D | 271 (7.3) | 0.25 (0.21–0.32) | 24.7 | 18.1 | 13.3 | 11.1 | 10.1 |
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Initial treatment modalities (n=4,496, missing values=76) | |||||||
Surgical resection | 888 (19.8) | NR (NR-NR) | 93.9 | 88.2 | 82.7 | 79.5 | 77.5 |
Liver transplantation | 51 (1.1) | NR (NR-NR) | 90.2 | 78.4 | 68.6 | 64.7 | 62.2 |
Local ablation therapy | 464 (10.3) | NR (NR-NR) | 94.8 | 89.4 | 83.0 | 77.2 | 74.2 |
Transarterial therapy | 1,675 (37.3) | 2.53 (2.38–2.86) | 73.8 | 57.1 | 46.3 | 39.8 | 35.5 |
Combination therapy† | 113 (2.5) | 3.60 (2.85–NR) | 69.9 | 61.9 | 57.5 | 47.8 | 45.0 |
Systemic therapy | 211 (4.7) | 0.35 (0.32–0.40) | 18.0 | 8.1 | 6.6 | 4.7 | 4.7 |
External beam radiation therapy | 60 (1.3) | 0.59 (0.50–0.80) | 26.7 | 16.7 | 10.0 | 10.0 | 10.0 |
Best supportive care | 857 (19.1) | 0.31 (0.28–0.34) | 28.1 | 20.4 | 16.1 | 13.2 | 12.0 |
Miscellaneous therapies‡ | 177 (3.9) | 1.38 (0.98–1.86) | 55.4 | 40.1 | 34.5 | 31.6 | 30.4 |
OS, overall survival; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; NR, not reached; UICC, Union for International Cancer Control; BCLC, Barcelona Clinic Liver Cancer.