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Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome Analysis

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Abstract

Objectives

Transarterial chemoembolization (TACE) improves the survival of patients with hepatocellular carcinoma (HCC); however, TACE treatment outcomes of patients with treatment-naïve HCC (TN-HCC) and those with recurrent HCC after curative resection (R-HCC) have not yet been compared.

Methods

We recruited 448 patients with TN-HCC, and 275 patients with R-HCC treated with TACE as first-line anti-cancer treatment.

Results

At first TACE, patients with TN-HCC showed a significantly lower proportion of male gender (74.9% vs. 84.3%), higher proportion of liver cirrhosis (61.9% vs. 49.3%), higher aspartate aminotransferase (median 48 vs. 31 IU/L), alanine aminotransferase (median 38 vs. 26 IU/L), alpha-fetoprotein (AFP) (median 96.6 vs. 7.7 ng/mL), and total bilirubin (mean 1.0 vs. 0.8 mg/dL) levels, longer prothrombin time (median 1.05 vs. 1.01 international normalized ratio), higher tumor number (mean 2.1 vs. 1.7), larger tumor size (median 3.1 vs. 1.6 cm), and lower proportion of Barcelona Clinic Liver Cancer stage 0-A (55.6% vs. 71.9%) than patients with R-HCC (all P < 0.05). Multivariate analysis showed that TACE for TN-HCC (vs. R-HCC) was an independent predictor of mortality (hazard ratio, 1.328; P = 0.024) with AFP level and tumor number (all P < 0.05). However, treatment outcomes between TN-HCC and R-HCC became statistically similar after propensity score-matched (PSM) analysis using liver cirrhosis, tumor size, and multiple tumors (P < 0.05).

Conclusions

Based on the similar TACE treatment outcomes observed with the PSM analysis, the current TACE treatment guideline for patients with TN-HCC might similarly be applied for patients with R-HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

TACE:

Transarterial chemoembolization

BCLC:

Barcelona Clinic Liver Cancer

PSM:

Propensity score-matched

TN-HCC:

Treatment-naïve HCC

R-HCC:

Recurrent HCC after curative resection

MRI:

Magnetic resonance imaging

CT:

Computed tomography

IQR:

Interquartile range

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

AFP:

Alpha-fetoprotein

HR:

Hazard ratio

CI:

Confidence interval

References

  1. Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(1264–1273):e1261.

    Google Scholar 

  3. Balogh J, Victor D, Asham EH, et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016;3:41–53.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Daher S, Massarwa M, Benson AA, et al. Current and future treatment of hepatocellular carcinoma: an updated comprehensive review. J Clin Transl Hepatol. 2018;6:69–78.

    PubMed  Google Scholar 

  5. Song MJ, Bae SH. Newer treatments for advanced hepatocellular carcinoma. Korean J Intern Med. 2014;29:149–155.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lee EW, Khan S. Recent advances in transarterial embolotherapies in the treatment of hepatocellular carcinoma. Clin Mol Hepatol. 2017;23:265–272.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dika IE, Abou-Alfa GK. Treatment options after sorafenib failure in patients with hepatocellular carcinoma. Clin Mol Hepatol. 2017;23:273–279.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhao YN, Zhang YQ, Ye JZ, et al. Hepatic resection versus transarterial chemoembolization for patients with barcelona clinic liver cancer intermediate stage child-pugh a hepatocellular carcinoma. Exp Ther Med. 2016;12:3813–3819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang JH, Changchien CS, Hu TH, et al. The efficacy of treatment schedules according to barcelona clinic liver cancer staging for hepatocellular carcinoma—survival analysis of 3892 patients. Eur J Cancer. 2008;44:1000–1006.

    Article  PubMed  Google Scholar 

  10. Yin X, Zhang L, Wang YH, et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma. BMC Cancer. 2014;14:849.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lacaze L, Scotté M. Surgical treatment of intra hepatic recurrence of hepatocellular carcinoma. World J Hepatol. 2015;7:1755–1760.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243:229–235.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Xu XS, Liu C, Qu K, et al. Liver transplantation versus liver resection for hepatocellular carcinoma: a meta-analysis. Hepatobiliary Pancreat Dis Int. 2014;13:234–241.

    Article  PubMed  Google Scholar 

  14. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442.

    Article  CAS  PubMed  Google Scholar 

  15. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.

    Article  PubMed  Google Scholar 

  16. Kudo M, Arizumi T, Ueshima K, et al. Subclassification of BCLC B stage hepatocellular carcinoma and treatment strategies: proposal of modified Bolondi’s subclassification (Kinki criteria). Dig Dis. 2015;33:751–758.

    Article  PubMed  Google Scholar 

  17. Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg. 2000;232:10–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Choi JW, Park JY, Ahn SH, et al. Efficacy and safety of transarterial chemoembolization in recurrent hepatocellular carcinoma after curative surgical resection. Am J Clin Oncol. 2009;32:564–569.

    Article  CAS  PubMed  Google Scholar 

  19. Anonymous. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908-943.

  20. Jung KS, Kim SU, Ahn SH, et al. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology. 2011;53:885–894.

    Article  CAS  PubMed  Google Scholar 

  21. Makuuchi M, Kosuge T, Takayama T, et al. Surgery for small liver cancers. Semin Surg Oncol. 1993;9:298–304.

    Article  CAS  PubMed  Google Scholar 

  22. Couinaud C. Le foie; études anatomiques et chirurgicales. Paris: Masson; 1957.

    Google Scholar 

  23. Kim SU, Kim BK, Han KH. Clinical application of liver stiffness measurement using transient elastography: a surgical perspective. Digestion. 2013;88:258–265.

    Article  PubMed  Google Scholar 

  24. Kim SU, Ahn SH, Park JY, et al. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan(®)) before curative resection of hepatocellular carcinoma: a pilot study. Hepatol Int. 2008;2:471–477.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee SH, Kim SU, Jang JW, et al. Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma. Onco Targets Ther. 2015;8:347–356.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kim BK, Shim JH, Kim SU, et al. Risk prediction for patients with hepatocellular carcinoma undergoing chemoembolization: development of a prediction model. Liver Int. 2016;36:92–99.

    Article  CAS  PubMed  Google Scholar 

  27. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171.

    Article  CAS  PubMed  Google Scholar 

  28. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224:47–54.

    Article  PubMed  Google Scholar 

  29. Colecchia A, Schiumerini R, Cucchetti A, et al. Prognostic factors for hepatocellular carcinoma recurrence. World J Gastroenterol. 2014;20:5935–5950.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010–2016. Clin Mol Hepatol. 2016;22:7–17.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim BK, Ahn SH, Seong JS, et al. Early alpha-fetoprotein response as a predictor for clinical outcome after localized concurrent chemoradiotherapy for advanced hepatocellular carcinoma. Liver Int. 2011;31:369–376.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2016R1A1A1A05005138). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    David Sooik Kim, Tae Seop Lim, Mi Young Jeon, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han & Seung Up Kim

  2. Yonsei Liver Center, Severance Hospital, Seoul, South Korea

    Tae Seop Lim, Mi Young Jeon, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han & Seung Up Kim

  3. Department of Infectious Diseases, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia

    Oidov Baatarkhuu

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  1. David Sooik Kim
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Contributions

DS Kim and SU Kim designed this study; DS Kim and SU Kim carried out the data analysis and wrote the manuscript; TS Lim, MY Jeon, BK Kim, JY Park, DY Kim, SH Ahn, KH Han, O Baatarkhuu, and SU Kim contributed to inclusion of patients, acquisition and analysis of data; all authors contributed to the interpretation of results, critical revision of the manuscript, and approved the final manuscript; SU Kim is the guarantor.

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Correspondence to Seung Up Kim.

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Supplementary material 1 (DOCX 19 kb)

10620_2019_5701_MOESM2_ESM.eps

Supplementary figure 1. Cumulative overall survival rates of the entire study population (A), TN-HCC subgroup (B), and R-HCC subgroup (C). The median follow-up period of the entire study population was 32.4 (interquartile range [IQR], 17.3–61.4) months. The cumulative survival rates at 2, 4, 6, 8, and 10 years were 64.7%, 33.2%, 15.5%, 4.4%, and 1.4%, respectively. The median follow-up periods of the TN-HCC and R-HCC patients were statistically similar (35.0 [IQR, 12.5–65.1] vs. 31.8 [IQR, 18.7–59.2], P = 0.813). The cumulative survival rates of the TN-HCC and R-HCC patients were 61.3% and 51.1% at 2 years, 36.8% and 31.0% at 4 years, 13.1% and 17.0% at 6 years, 3.3% and 5.1% at 8 years, and 1.1% and 1.6% at 10 years, respectively. TN-HCC, treatment-naïve hepatocellular carcinoma; R-HCC, recurrent hepatocellular carcinoma; IQR, interquartile range (EPS 2419 kb)

10620_2019_5701_MOESM3_ESM.eps

Supplementary figure 2. Cumulative overall survival rates by AFP (A) and treatment group (TACE for TN-HCC vs. TACE for early recurrent HCC) (B). In the early recurrent HCC and TN-HCC cohorts, the cumulative survival rate of patients with a high AFP level (>400 ng/mL) was significantly lower than that of patients with a low AFP level (≤400 ng/mL) (P < 0.001, log-rank test). Similarly, the cumulative survival rate of patients with multiple tumors was significantly lower than that of patients with a single tumor (P < 0.001, log-rank test). However, the cumulative survival rate of patients with TN-HCC was not significantly different from that of patients with R-HCC (P = 0.068, log-rank test). AFP, alpha-fetoprotein; TACE, transarterial chemoembolization; TN-HCC, treatment-naïve hepatocellular carcinoma; R-HCC, recurrent hepatocellular carcinoma (EPS 2495 kb)

10620_2019_5701_MOESM4_ESM.eps

Supplementary figure 3. Cumulative overall survival rates by AFP level (A), tumor number (B), and treatment group (TACE for TN-HCC vs. TACE for late recurrent HCC) (C). In the late recurrent HCC and TN-HCC cohorts, the cumulative survival rate of patients with a high AFP level (>400 ng/mL) was significantly lower than that of patients with a low AFP level (≤400 ng/mL) (P < 0.001, log-rank test). Similarly, the cumulative survival rate of patients with TN-HCC was significantly lower than that of patients with late recurrent HCC in addition to multiple tumors (all P < 0.001, log-rank test). AFP, alpha-fetoprotein; TACE, transarterial chemoembolization; TN-HCC, treatment-naïve hepatocellular carcinoma; R-HCC, recurrent hepatocellular carcinoma (EPS 1884 kb)

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Kim, D.S., Lim, T.S., Jeon, M.Y. et al. Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome Analysis. Dig Dis Sci 64, 3660–3668 (2019). https://doi.org/10.1007/s10620-019-05701-8

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