Real Life Prospective Evaluation of New Drug-Eluting Platform for Chemoembolization of Patients with Hepatocellular Carcinoma: PARIS Registry

Thierry de Baere, Boris Guiu, Maxime Ronot, Patrick Chevallier, Géraldine Sergent, Illario Tancredi, Lambros Tselikas, Marco Dioguardi Burgio, Lucas Raynaud, Frederic Deschamps, Gontran Verset, Thierry de Baere, Boris Guiu, Maxime Ronot, Patrick Chevallier, Géraldine Sergent, Illario Tancredi, Lambros Tselikas, Marco Dioguardi Burgio, Lucas Raynaud, Frederic Deschamps, Gontran Verset

Abstract

Background and aim: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearlTM, loaded with anthracyclines.

Materials and methods: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearlTM loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years.

Results: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1-2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)).

Conclusions: DEM-TACE using LifePearlTM provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearlTM. The trial was registered in ClinicalTrials.gov National Library of Medicine (ID: NCT03053596).

Keywords: DEM-TACE; doxorubicin; hepatobiliary toxicities; hepatocellular carcinoma; idarubicin.

Conflict of interest statement

The authors declare following conflict of interest: Thierry de Baere is consultant for Astra-Zeneca, Boston-Scientific, Guerbet, Medtronic, Terumo; Boris Guiu is consultant for Boston-Scientific, Terumo, Guerbet, Roche, Quantum Surgical. Maxime Ronot is consultant for Quantum Surgical; Lambros Tselikas is consultant for BMS, Boston Scientific, General Electric and received grants from BMS and Terumo; Frederick Deschamps is consultant for GE Healthcare, Medtronic, Terumo, Ablatech; Gontran Verset is consultant for Bayer, BTG, Terumo, Eisai and Roche; other authors do not have any conflict of interest to declare. The study sponsor has contributed to study conception, study management and source data verification. However, the study sponsor did not influence the decision to publish data, nor the interpretation of the results. The corresponding author, the coordinating investigator of the study, had full access to data and takes final responsibility for submission of the manuscript.

Figures

Figure 1
Figure 1
Multivariate analysis for the prediction of hepatobiliary toxicities (Logistic regression models).
Figure 2
Figure 2
Kaplan–Meier Analysis: progression free survival (overall and target lesion) and time to transarterial chemoembolization (TACE) untreatable progression.
Figure 3
Figure 3
Alpha-fetoprotein (AFP) change between baseline and first follow-up.
Figure 4
Figure 4
Overall survival (HBT = hepatobiliary toxicities).
Figure 5
Figure 5
Multivariate analysis for the prediction of overall survival (Cox regression model).

References

    1. McGlynn K.A., Petrick J.L., London W.T. Global epidemiology of hepatocellular carcinoma: An emphasis on demographic and regional variability. Clin. Liver Dis. 2015;19:223–238. doi: 10.1016/j.cld.2015.01.001.
    1. European Association for the Study of the Liver. European Organisation for Research and Treatment of Cancer EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2012;56:908–943. doi: 10.1016/j.jhep.2011.12.001.
    1. Mokdad A.A., Hester C.A., Singal A.G., Yopp A.C. Management of hepatocellular in the United States. Chin. Clin. Oncol. 2017;6:21. doi: 10.21037/cco.2017.04.04.
    1. Bruix J., Reig M., Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology. 2016;150:835–853. doi: 10.1053/j.gastro.2015.12.041.
    1. Raoul J.L., Forner A., Bolondi L., Cheung T.T., Kloeckner R., de Baere T. Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence. Cancer Treat. Rev. 2019;72:28–36. doi: 10.1016/j.ctrv.2018.11.002.
    1. Guiu B., Deschamps F., Aho S., Munck F., Dromain C., Boige V., Malka D., Leboulleux S., Ducreux M., Schlumberger M., et al. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: Lipiodol vs. drug-eluting beads. J. Hepatol. 2012;56:609–617. doi: 10.1016/j.jhep.2011.09.012.
    1. Monier A., Guiu B., Duran R., Aho S., Bize P., Deltenre P., Dunet V., Denys A. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: Comparison between drug-eluting beads and lipiodol emulsion. Eur. Radiol. 2017;27:1431–1439. doi: 10.1007/s00330-016-4488-y.
    1. De Baere T., Plotkin S., Yu R., Sutter A., Wu Y., Cruise G.M. An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin. J. Vasc. Interv. Radiol. 2016;27:1425–1431. doi: 10.1016/j.jvir.2016.05.015.
    1. Aliberti C., Carandina R., Lonardi S., Dadduzio V., Vitale A., Gringeri E., Zanus G., Cillo U. Transarterial Chemoembolization with Small Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: Experience from a Cohort of 421 Patients at an Italian Center. J. Vasc. Interv. Radiol. 2017;28:1495–1502. doi: 10.1016/j.jvir.2017.07.020.
    1. Gomes F.V., Oliveira J.A., Correia M.T., Costa N.V., Abrantes J., Torres D., Pereira P., Ferreira A.I., Luz J.H., Spaepen E., et al. Chemoembolization of Hepatocellular Carcinoma with Drug-Eluting Polyethylene Glycol Embolic Agents: Single-Center Retrospective Analysis in 302 Patients. J. Vasc. Interv. Radiol. 2018;29:841–849. doi: 10.1016/j.jvir.2018.02.004.
    1. Fiorentini G., Sarti D., Carandina R., Mulazzani L., Mincarelli C., Candelari R., Argirò R., Fiorentini C., Aliberti C. A review discussing the use of polyethylene glycol microspheres in the treatment of hepatocellular carcinoma. Future Oncol. 2019;15:695–703. doi: 10.2217/fon-2018-0425.
    1. Lucatelli P., Corradini L.G., De Rubeis G., Rocco B., Basilico F., Cannavale A., Nardis P.G., Corona M., Saba L., Catalano C., et al. Balloon-Occluded Transcatheter Arterial Chemoembolization (b-TACE) for Hepatocellular Carcinoma Performed with Polyethylene-Glycol Epirubicin-Loaded Drug-Eluting Embolics: Safety and Preliminary Results. Cardiovasc. Interv. Radiol. 2019;42:853–862. doi: 10.1007/s00270-019-02192-y.
    1. Aliberti C., Carandina R., Sarti D., Mulazzani L., Catalano V., Felicioli A., Coschiera P., Fiorentini G. Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy. Anticancer. Res. 2016;36:3515–3521.
    1. Aliberti C., Carandina R., Sarti D., Mulazzani L., Pizzirani E., Guadagni S., Fiorentini G. Chemoembolization Adopting Polyethylene Glycol Drug-Eluting Embolics Loaded With Doxorubicin for the Treatment of Hepatocellular Carcinoma. AJR Am. J. Roentgenol. 2017;209:430–434. doi: 10.2214/AJR.16.17477.
    1. Boulin M., Hillon P., Cercueil J.P., Bonnetain F., Dabakuyo S., Minello A., Jouve J.L., Lepage C., Bardou M., Wendremaire M., et al. Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: Results of the IDASPHERE phase I trial. Aliment. Pharmacol. Ther. 2014;39:1301–1313. doi: 10.1111/apt.12746.
    1. Guiu B., Colombat S., Piron L., Hermida M., Allimant C., Pierredon-Foulogne M.-A., Belgour A., Escal L., Cassinotto C., Boulin M. Transarterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin-Loaded Tandem Drug-Eluting Embolics. Cancers. 2019;11:987. doi: 10.3390/cancers11070987.
    1. Lammer J., On Behalf of the PRECISION V Investigators. Malagari K., Vogl T., Pilleul F., Denys A., Watkinson A., Pitton M., Sergent G., Pfammatter T., et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: Results of the PRECISION V study. Cardiovasc. Interv. Radiol. 2010;33:41–52. doi: 10.1007/s00270-009-9711-7.
    1. Golfieri R., on behalf of the PRECISION ITALIA STUDY GROUP. Giampalma E., Renzulli M., Cioni R., Bargellini I., Bartolozzi C., Breatta A.D., Gandini G., Nani R., et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br. J. Cancer. 2014;111:255–264. doi: 10.1038/bjc.2014.199.
    1. Llovet J.M., Real M.I., Montaña X., Planas R., Coll S., Aponte J., Ayuso C., Sala M., Muchart J., Solà R., et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet. 2002;359:1734–1739. doi: 10.1016/S0140-6736(02)08649-X.
    1. Lo C.-M., Ngan H., Tso W.-K., Liu C.-L., Lam C.-M., Poon R.T.-P., Fan S.T., Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171. doi: 10.1053/jhep.2002.33156.
    1. Mazzaferro V., Citterio D., Bhoori S., Bongini M., Miceli R., De Carlis L., Colledan M., Salizzoni M., Romagnoli R., Antonelli B., et al. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): A randomised, controlled, phase 2b/3 trial. Lancet Oncol. 2020;21:947–956. doi: 10.1016/S1470-2045(20)30224-2.
    1. Finn R.S., Qin S., Ikeda M., Galle P.R., Ducreux M., Kim T.-Y., Kudo M., Breder V., Merle P., Kaseb A.O., et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020;382:1894–1905. doi: 10.1056/NEJMoa1915745.
    1. Joskin J., De Baere T., Auperin A., Tselikas L., Guiu B., Farouil G., Boige V., Malka D., Leboulleux S., Ducreux M., et al. Predisposing factors of liver necrosis after transcatheter arterial chemoembolization in liver metastases from neuroendocrine tumor. Cardiovasc. Interv. Radiol. 2015;38:372–380. doi: 10.1007/s00270-014-0914-1.
    1. Nakada S., Allard M.-A., Lewin M., Awad S., Dahbi N., Nitta H., Cunha A.S., Castaing D., Vibert E., Cherqui D., et al. Ischemic Cholangiopathy Following Transcatheter Arterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy: An Underestimated and Devastating Complication. J. Gastrointest. Surg. 2019 doi: 10.1007/s11605-019-04409-4.
    1. Burrel M., Reig M., Forner A., Barrufet M., De Lope C.R., Tremosini S., Ayuso C., Llovet J.M., Real M.I., Bruix J. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. J. Hepatol. 2012;56:1330–1335. doi: 10.1016/j.jhep.2012.01.008.
    1. Ikeda M., Arai Y., Park S.J., Takeuchi Y., Anai H., Kim J.K., Inaba Y., Aramaki T., Kwon S.H., Yamamoto S., et al. Prospective study of transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: An Asian cooperative study between Japan and Korea. J. Vasc. Interv. Radiol. 2013;24:490–500. doi: 10.1016/j.jvir.2013.01.003.
    1. Aal A.K.A., Moawad S., Lune P.V., El Khudari H., Hanaoka M.M., AboulDahab N., Gunn A.J., White J., Shoreibah M., Li Y., et al. Survival Outcomes of Very Small Drug-Eluting Beads Used in Chemoembolization of Unresectable Hepatocellular Carcinoma. J. Vasc. Interv. Radiol. 2019;30:1325–1334.e2. doi: 10.1016/j.jvir.2019.05.006.
    1. García J.U., Echevarria-Uraga J.J., Ciampi-Dopazo J.J., Sánchez-Corral J.A., Alonso J.C., Anton-Ladislao A., Peña-Baranda B., Nacarino-Mejias V., González-Costero R., Ruiz-Canela J.J.M., et al. Multicentre prospective study of drug-eluting bead chemoembolisation safety using tightly calibrated small microspheres in non-resectable hepatocellular carcinoma. Eur. J. Radiol. 2020;126:108966. doi: 10.1016/j.ejrad.2020.108966.
    1. Wu S.-J., Lin Y.-X., Ye H., Xiong X.-Z., Li F.-Y., Cheng N.-S. Prognostic value of alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase in hepatocellular carcinoma patients treated with liver resection. Int. J. Surg. 2016;36:143–151. doi: 10.1016/j.ijsu.2016.10.033.
    1. Duan F., Wang E.Q., Lam M.G.E.H., Abdelmaksoud M.H., Louie J.D., Hwang G.L., Kothary N., Kuo W.T., Hofmann L.V., Sze D.Y. Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion. Radiology. 2016;278:612–621. doi: 10.1148/radiol.2015141417.
    1. Guiu B., Chevallier P., Assenat E., Barbier E., Merle P., Bouvier A., Dumortier J., Nguyen-Khac E., Gugenheim J., Rode A., et al. Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial. Radiology. 2019;291:801–808. doi: 10.1148/radiol.2019182399.
    1. Roth G.S., Teyssier Y., Abousalihac M., Seigneurin A., Ghelfi J., Sengel C., Decaens T. Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma. World J. Gastroenterol. 2020;26:324–334. doi: 10.3748/wjg.v26.i3.324.
    1. Lencioni R., De Baere T., Burrel M., Caridi J.G., Lammer J., Malagari K., Martin R.C.G., O’Grady E., Real M.I., Vogl T.J., et al. Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): Technical recommendations. Cardiovasc. Interv. Radiol. 2012;35:980–985. doi: 10.1007/s00270-011-0287-7.
    1. Lencioni R., Llovet J.M. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin. Liver Dis. 2010;30:52–60. doi: 10.1055/s-0030-1247132.

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