Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study
Abstract
:1. Introduction
2. Results
2.1. Demographics of the Two Groups after Propensity Score Matching (PSM)
2.2. Follow-Up and Survival Analysis Results
2.3. Subgroup Analysis
2.4. Major Complications Compared between Two Groups
2.5. Sensitivity Analysis of Survival Outcome
3. Discussion
4. Materials and Methods
4.1. Source of Data
4.2. Inclusion and Exclusion Criteria
4.3. Patient Accrual and Cohort Assembly
4.4. Propensity Score Matching
4.5. Outcome Measures
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristics | Before Propensity-Score Matching | After Propensity-Score Matching | ||||||
---|---|---|---|---|---|---|---|---|
Without TACE (n = 3248; 88.4%) | With TACE (n = 426; 11.6%) | Standardized Mean Difference | p-Value | Without TACE (n = 1686; 79.8%) | With TACE (n = 426; 20.2%) | Standardized Mean Difference | p-Value | |
Age | ||||||||
Mean (Median) | 63.0 (63.1) | 59.3 (60.4) | −0.305 | 0.000 | 60.0 (60.0) | 59.3 (60.4) | −0.023 | 0.277 |
IQR | 55.2–72.5 | 50.7–68.7 | 51.8–67.8 | 50.7–68.7 | ||||
Gender, n (%) | ||||||||
Male | 2528 (77.8) | 355 (83.3) | 0.147 | 0.009 | 1410 (83.6) | 355 (83.3) | −0.013 | 0.883 |
Female | 720 (22.2) | 71 (16.7) | 276 (16.4) | 71 (16.7) | ||||
CCI, n (%) | ||||||||
0 | 53 (1.6) | 0 (0.0) | 0.395 | 0.000 | 3 (0.2) | 0 (0.0) | 0.007 | 0.682 |
1–2 | 413 (12.7) | 27 (6.3) | 105 (6.2) | 27 (6.3) | ||||
≥3 | 2782 (85.7) | 399 (93.7) | 1578 (93.6) | 399 (93.7) | ||||
Insurance premium category | ||||||||
Lowest | 429 (13.2) | 53 (12.4) | 0.003 | 0.357 | 194 (11.5) | 53 (12.4) | −0.015 | 0.320 |
Low | 1121 (34.5) | 146 (34.3) | 515 (30.5) | 146 (34.3) | ||||
Medium | 931 (28.7) | 122 (28.6) | 584 (34.6) | 122 (28.6) | ||||
High | 79 (2.4) | 16 (3.8) | 54 (3.2) | 16 (3.8) | ||||
Highest | 196 (6.0) | 33 (7.7) | 123 (7.3) | 33 (7.7) | ||||
Hospital status | ||||||||
Academic center | 2209 (68.0) | 321 (75.4) | 0.170 | 0.002 | 1268 (75.2) | 321 (75.4) | −0.03 | 0.951 |
Non-academic center | 1039 (32.0) | 105 (24.6) | 418 (24.8) | 105 (24.6) | ||||
Metastasis | ||||||||
Lymph nodes | 174 (5.4) | 29 (6.8) | 0.058 | 0.218 | 110 (6.5) | 29 (6.8) | 0.006 | 0.833 |
Lungs | 599 (18.4) | 90 (21.1) | 0.066 | 0.182 | 340 (20.2) | 90 (21.1) | 0.019 | 0.660 |
Adrenal gland | 59 (1.8) | 9 (2.1) | 0.021 | 0.670 | 37 (2.2) | 9 (2.1) | −0.004 | 0.918 |
Bone | 341 (10.5) | 55 (12.9) | 0.072 | 0.131 | 211 (12.5) | 55 (12.9) | 0.003 | 0.826 |
Peritoneum | 82 (2.5) | 14 (3.3) | 0.043 | 0.354 | 55 (3.3) | 14 (3.3) | −0.016 | 0.980 |
Type 2 diabetes | ||||||||
Yes | 534 (16.4) | 84 (19.7) | 0.082 | 0.089 | 332 (19.7) | 84 (19.7) | −0.002 | 0.990 |
No | 2909 (84.4) | 350 (80.6) | 1354 (80.3) | 342 (80.3) | ||||
Metformin use | ||||||||
Yes | 407 (12.5) | 60 (14.1) | 0.045 | 0.365 | 239 (14.2) | 60 (14.1) | −0.006 | 0.962 |
No | 3034 (88.1) | 374 (86.2) | 1447 (85.8) | 366 (85.9) | ||||
Alcoholic liver disease | ||||||||
Yes | 128 (3.9) | 26 (6.1) | 0.090 | 0.036 | 97 (5.8) | 26 (6.0) | 0.005 | 0.783 |
No | 3120 (96.1) | 400 (93.9) | 1589 (94.2) | 400 (93.9) | ||||
Chronic kidney disease | ||||||||
Yes | 109 (3.4) | 12 (2.8) | −0.033 | 0.558 | 45 (2.7) | 12 (2.8) | 0.011 | 0.866 |
No | 3139 (96.6) | 414 (97.2) | 1641 (97.3) | 414 (97.2) |
Outcome Measures | Sorafenib + TACE n = 426 | Sorafenib Alone n = 1686 | Hazard Ratio (95% Confidence Interval, CI) | p-Value |
---|---|---|---|---|
Median follow-up (Quartile) days | 221 (140–345) | 133 (68–251) | - | - |
Outcome N (%) Deaths | 164 (38.5) | 916 (54.3) | - | 0.000 |
Median overall survival (OS) in days (95% CI) | 381 (327–435) | 204 (188–221) | 0.74 * (0.63–0.88) | 0.021 |
Median overall survival (OS) in months (95% CI) | 12.5 (10.8–14.3) | 6.7 (6.2–7.3) | ||
6-month OS | 80.3% | 54.4% | - | - |
1-year OS | 53.5% | 32.4% | - | - |
Median time (days) to sorafenib discontinuation (95% CI) | 144 (127–161) | 86 (80–92) | 0.76 (0.65–0.89) | 0.001 |
Median time (mo.) to sorafenib discontinuation (95% CI) | 4.7 (4.2–5.3) | 2.8 (2.6–3.0) |
Major Event | Sorafenib + TACE Event(s) (SD) | Sorafenib Alone Event(s) (SD) | Odds Ratio † (95% CI) | p-Value |
---|---|---|---|---|
Rupture of hepatocellular carcinoma | 9 (2.1) | 34 (2.0) | 1.05 (0.50–2.20) | 0.900 |
Spontaneous bacterial peritonitis | 11 (2.6) | 76 (4.5) | 0.56 (0.30–1.07) | 0.74 |
Esophageal variceal hemorrhage | 9 (2.1) | 28 (1.7) | 1.28 (0.60–2.73) | 0.525 |
Hepatic encephalopathy | 48 (11.3) | 251 (14.9) | 0.73 (0.52–1.01) | 0.056 |
Hepatic failure | 7 (1.6) | 12 (0.7) | 2.33 (0.91–5.96) | 0.069 |
Disseminated intravascular coagulopathy | 1 (0.2) | 4 (0.2) | 0.99 (0.11–8.88) | 0.992 |
Measures | Sorafenib Alone n = 1686 (Reference) | Sorafenib + TACE × 1 n = 293 | Sorafenib + TACE ≥ 2 n = 133 | ||
---|---|---|---|---|---|
Median follow-up (Quartile) days | 133 (68–251) | 196 (117–303) | 313 (195–420) | ||
Outcome N (%) Deaths | 916 (54.3) | 125 (42.7) | 39 (29.3) | ||
Median overall survival in days (95% CI) | 204 (188–221) | 315 (292–338) | Adjusted HR * = 0.97 (95% CI, 0.80–1.18) | NR | Adjusted HR * = 0.41 (95% CI, 0.29–0.56) |
Median overall survival in months (95% CI) | 6.7 (6.2–7.3) | 10.4 (9.6–11.1) | NR |
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Share and Cite
Kok, V.C.; Chen, Y.-C.; Chen, Y.-Y.; Su, Y.-C.; Ku, M.-C.; Kuo, J.-T.; Yoshida, G.J. Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study. Cancers 2019, 11, 985. https://doi.org/10.3390/cancers11070985
Kok VC, Chen Y-C, Chen Y-Y, Su Y-C, Ku M-C, Kuo J-T, Yoshida GJ. Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study. Cancers. 2019; 11(7):985. https://doi.org/10.3390/cancers11070985
Chicago/Turabian StyleKok, Victor C., Yu-Ching Chen, Yang-Yuan Chen, Yu-Chieh Su, Ming-Chang Ku, Jung-Tsung Kuo, and Go J. Yoshida. 2019. "Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study" Cancers 11, no. 7: 985. https://doi.org/10.3390/cancers11070985