Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis

  • Myungsu Lee (Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jin Wook Chung (Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Kwang-Hun Lee (Department of Radiology, Gangnam Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Jong Yun Won (Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Ho Jong Chun (Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Han Chu Lee (Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jin Hyoung Kim (Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • In Joon Lee (Department of Radiology, National Cancer Center) ;
  • Saebeom Hur (Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Hyo-Cheol Kim (Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Yoon Jun Kim (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Gyoung Min Kim (Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Seung-Moon Joo (Department of Radiology, Gangnam Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine) ;
  • Jung Suk Oh (Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2019.10.21
  • Accepted : 2021.02.22
  • Published : 2021.10.01
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Abstract

Objective: To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). Materials and Methods: This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and per-lesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. Results: The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). Conclusion: DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.

Keywords

Acknowledgement

This study was supported, in the form of a grant and provision of drug-eluting embolics, by Biocompatibles UK (Farnham, United Kingdom).

References

  1. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-1739  https://doi.org/10.1016/S0140-6736(02)08649-X
  2. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-1171  https://doi.org/10.1053/jhep.2002.33156
  3. Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int 2015;35:2155-2166  https://doi.org/10.1111/liv.12818
  4. Idee JM, Guiu B. Use of lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013;88:530-549  https://doi.org/10.1016/j.critrevonc.2013.07.003
  5. Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007;30:6-25  https://doi.org/10.1007/s00270-006-0062-3
  6. Lewis AL, Gonzalez MV, Lloyd AW, Hall B, Tang Y, Willis SL, et al. DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol 2006;17:335-342  https://doi.org/10.1097/01.RVI.0000195323.46152.B3
  7. Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF. New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 2006;12:2563-2567  https://doi.org/10.1158/1078-0432.CCR-05-2225
  8. Lewis AL, Taylor RR, Hall B, Gonzalez MV, Willis SL, Stratford PW. Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol 2006;17:1335-1343  https://doi.org/10.1097/01.RVI.0000228416.21560.7F
  9. Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 2007;46:474-481  https://doi.org/10.1016/j.jhep.2006.10.020
  10. Poon RT, Tso WK, Pang RW, Ng KK, Woo R, Tai KS, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 2007;5:1100-1108  https://doi.org/10.1016/j.cgh.2007.04.021
  11. Golfieri R, Giampalma E, Renzulli M, Cioni R, Bargellini I, Bartolozzi C, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 2014;111:255-264  https://doi.org/10.1038/bjc.2014.199
  12. Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010;33:41-52  https://doi.org/10.1007/s00270-009-9711-7
  13. Sacco R, Bargellini I, Bertini M, Bozzi E, Romano A, Petruzzi P, et al. Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2011;22:1545-1552  https://doi.org/10.1016/j.jvir.2011.07.002
  14. Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol 2010;101:476-480  https://doi.org/10.1002/jso.21522
  15. Song MJ, Chun HJ, Song DS, Kim HY, Yoo SH, Park CH, et al. Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol 2012;57:1244-1250  https://doi.org/10.1016/j.jhep.2012.07.017
  16. Liu YS, Ou MC, Tsai YS, Lin XZ, Wang CK, Tsai HM, et al. Transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of hepatocellular carcinoma. Korean J Radiol 2015;16:125-132  https://doi.org/10.3348/kjr.2015.16.1.125
  17. Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol 2016;34:2046-2053  https://doi.org/10.1200/JCO.2015.64.0821
  18. Lee M, Chung JW, Lee KH, Won JY, Chun HJ, Lee HC, et al. Korean multicenter registry of transcatheter arterial chemoembolization with drug-eluting embolic agents for nodular hepatocellular carcinomas: six-month outcome analysis. J Vasc Interv Radiol 2017;28:502-512  https://doi.org/10.1016/j.jvir.2016.08.017
  19. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60  https://doi.org/10.1055/s-0030-1247132
  20. Seki A, Hori S, Shimono C. Management of vascular lake phenomenon on angiography during chemoembolization with superabsorbent polymer microspheres. Jpn J Radiol 2015;33:741-748  https://doi.org/10.1007/s11604-015-0486-2
  21. Malagari K, Pomoni M, Kelekis A, Pomoni A, Dourakis S, Spyridopoulos T, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010;33:541-551  https://doi.org/10.1007/s00270-009-9750-0
  22. Martin RC 2nd, Rustein L, Perez Enguix D, Palmero J, Carvalheiro V, Urbano J, et al. Hepatic arterial infusion of doxorubicin-loaded microsphere for treatment of hepatocellular cancer: a multi-institutional registry. J Am Coll Surg 2011;213:493-500  https://doi.org/10.1016/j.jamcollsurg.2011.07.010
  23. Malagari K, Pomoni M, Moschouris H, Bouma E, Koskinas J, Stefaniotou A, et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Intervent Radiol 2012;35:1119-1128  https://doi.org/10.1007/s00270-012-0394-0
  24. Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 2010;30:61-74  https://doi.org/10.1055/s-0030-1247133
  25. Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 2014;146:1691-1700.e3  https://doi.org/10.1053/j.gastro.2014.02.032
  26. The Cancer of the Liver Italian Program (CLIP) investigators. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology 1998;28:751-755  https://doi.org/10.1002/hep.510280322
  27. Choi JW, Chung JW, Lee DH, Kim HC, Hur S, Lee M, et al. Portal hypertension is associated with poor outcome of transarterial chemoembolization in patients with hepatocellular carcinoma. Eur Radiol 2018;28:2184-2193  https://doi.org/10.1007/s00330-017-5145-9
  28. Kobayashi S, Nakanuma Y, Matsui O. Intrahepatic peribiliary vascular plexus in various hepatobiliary diseases: a histological survey. Hum Pathol 1994;25:940-946 https://doi.org/10.1016/0046-8177(94)90016-7