Safety and efficacy of DEM-TACE performed with drug-eluting microspheres smaller than 300 μm in patients with HCC and TIPS

Abstract

Aim: Safety and efficacy evidence of drug-eluting-microspheres trans-arterial chemoembolization (DEM-TACE) in patients with hepatocellular carcinoma (HCC) and trans-jugular intrahepatic portosystemic shunt (TIPS) is lacking. The aim of this retrospective study was to report the safety and efficacy of DEM-TACE procedures performed with microspheres smaller than 300 μm in patients with HCC and TIPS in a high-volume transplant center.

Methods: Embolization was standardized by initiating DEM-TACE with microspheres smaller than 100 μm, and if stasis was not achieved, adjunctive embolization with 100-300 or 200 μm microspheres was administered. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria at 1, 3-6, 9-12, and 15-18 months. Reporting the safety profile, detailed laboratory analysis was performed before, at 36-48 h, and 30-60 days after the procedure. Adverse events (AEs) were recorded; post-embolic syndrome was defined as the onset of fever/nausea/pain after the procedure. Late onset hepatobiliary complications were evaluated by follow-up imaging with computed tomography or magnetic resonance (CT/MR).

Results: From December 2007 to November 2020, 17 HCC patients (25 HCC nodules) with patent TIPS underwent 20 DEM-TACE. Embolization was performed only with microspheres smaller than 100 μm in 3/20 DEM-TACE (15%); adjunctive embolization with 100-300 or 200 μm microspheres was required in 17/20 DEM-TACE (85%). Reported early AEs were post-embolic syndrome (9/20; 45%) all of grade 1-2, late AEs were asymptomatic acute liver bile duct injury (2/20; 10%), and in one case we observed hepatic abscess (1/20; 5%) resulting in death due to sepsis. With regards to efficacy, the oncological response was evaluated and categorized according to mRECIST criteria. Complete response (CR) at 1, 3-6, 9-12, and 15-18 months was 52%, 50%, 50%, and 50%, respectively. Objective response (CR + partial response) at 1, 3-6, 9-12, and 15-18 months was 95%, 71%, 70%, and 50%, respectively.

Conclusion: DEM-TACE with drug-eluting-microspheres smaller than 300 μm can be performed in appropriately selected patients with TIPS.

Keywords

HCC / TIPS / DEM-TACE / CT / MR

References

[1] Lo CM,Tso WK.Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology2002;35:1164-71

[2] Dariushnia SR,Midia M.; Society of Interventional Radiology Standards of Practice Committee. Quality Improvement Guidelines for Transjugular Intrahepatic Portosystemic Shunts.J Vasc Interv Radiol2016;27:1-7

[3] Lucatelli P,Guiu B.CIRSE standards of practice on hepatic transarterial chemoembolisation.Cardiovasc Intervent Radiol2021;44:1851-67

[4] Kuo YC,Naeger DM.Efficacy of TACE in TIPS patients: comparison of treatment response to chemoembolization for hepatocellular carcinoma in patients with and without a transjugular intrahepatic portosystemic shunt.Cardiovasc Intervent Radiol2013;36:1336-43 PMCID:PMC3870189

[5] Padia SA,Kogut MJ.Outcomes of locoregional tumor therapy for patients with hepatocellular carcinoma and transjugular intrahepatic portosystemic shunts.Cardiovasc Intervent Radiol2015;38:913-21

[6] Wang Z,Zhao H.Repeated transcatheter arterial chemoembolization is safe for hepatocellular carcinoma in cirrhotic patients with transjugular intrahepatic portosystemic shunt.Diagn Interv Radiol2014;20:487-91 PMCID:PMC4463286

[7] Padia SA,Bastawrous S.Safety and efficacy of drug-eluting bead chemoembolization for hepatocellular carcinoma: comparison of small-versus medium-size particles.J Vasc Interv Radiol2013;24:301-6

[8] Odisio BC,Yan Y.Transarterial hepatic chemoembolization with 70-150 µm drug-eluting beads: assessment of clinical safety and liver toxicity profile.J Vasc Interv Radiol2015;26:965-71 PMCID:PMC4484796

[9] de Baere T,Ronot M.Real life prospective evaluation of new drug-eluting platform for chemoembolization of patients with hepatocellular carcinoma: paris registry.Cancers (Basel)2020;12:3405 PMCID:PMC7698357

[10] Bruix J.American Association for the Study of Liver DiseasesManagement of hepatocellular carcinoma: an update.Hepatology2011;53:1020-2 PMCID:PMC3084991

[11] Lucatelli P,De Rubeis G.Polyethylene glycol epirubicin-loaded transcatheter arterial chemoembolization procedures utilizing a combined approach with 100 and 200 μm microspheres: a promising alternative to current standards.J Vasc Interv Radiol2019;30:305-13

[12] Facciorusso A,Muscatiello N,Barone M.Transarterial chemoembolization: evidences from the literature and applications in hepatocellular carcinoma patients.World J Hepatol2015;7:2009-19 PMCID:PMC4528274

[13] Lencioni R.Modified RECIST (mRECIST) assessment for hepatocellular carcinoma.Semin Liver Dis2010;30:52-60

[14] Lucatelli P,Ginanni Corradini S.Comparison of image quality and diagnostic performance of cone-beam ct during drug-eluting embolic transarterial chemoembolization and multidetector CT in the detection of hepatocellular carcinoma.J Vasc Interv Radiol2017;28:978-86

[15] Wang Z,Duan F,Liu F.Bile duct injury after trans- catheter arterial chemoembolization: risk factors and clinical implications. Hepatogastroenterology 2014; 61:947-953.

[16] Choi JY,Sirlin CB.CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects.Radiology2014;272:635-54 PMCID:PMC4263631

[17] Liapi E.Transcatheter arterial chemoembolization for liver cancer: is it time to distinguish conventional from drug-eluting chemoembolization?.Cardiovasc Intervent Radiol2011;34:37-49 PMCID:PMC4352323

[18] Kang JW,Ko GY.Transarterial chemoembolization for hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt.Acta Radiol2012;53:545-50

[19] Kohi MP,Naeger DM.Hepatotoxicity after transarterial chemoembolization and transjugular intrahepatic portosystemic shunt: do two rights make a wrong?.J Vasc Interv Radiol2013;24:68-73

[20] Fan W,Zhu B.Drug-eluting beads TACE is safe and non-inferior to conventional TACE in HCC patients with TIPS.Eur Radiol2021;31:8291-301 PMCID:PMC8523393

[21] Chen X,Wang GB.Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.Diagn Interv Radiol2021;27:671-6 PMCID:PMC8480950

[22] Lammer J,Vogl T.; PRECISION V Investigators. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.Cardiovasc Intervent Radiol2010;33:41-52 PMCID:PMC2816794

[23] Grosso M,Quaretti P.Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicentre study.Cardiovasc Intervent Radiol2008;31:1141-9

[24] Malagari K,Alexopoulou E.Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients.Cardiovasc Intervent Radiol2008;31:269-80

[25] Kloeckner R,Prinz F.Conventional transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for the treatment of hepatocellular carcinoma.BMC Cancer2015;15:465 PMCID:PMC4460638

[26] Liu YS,Chuang MT.Five-year outcome of conventional and drug-eluting transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.BMC Gastroenterol2018;18:124 PMCID:PMC6091027

[27] Association for the Study of the Liver. Electronic address: [e-mail]; European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2018;69:182-236

[28] Varela M,Burrel M.Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics.J Hepatol2007;46:474-81

[29] Scheiner B,Mandorfer M.Short- and long-term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma.United European Gastroenterol J2019;7:850-8 PMCID:PMC6620878