Chemoembolization with Degradable Starch Microspheres (DSM-TACE): expanding indications in HCC multidisciplinary tumor board

Abstract

The role of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) management has changed over the last twenty years. There has been a trend towards an overall decline in TACE procedures, but with a more aggressive approach, repeating multiple TACE sessions in case of tumor response. The survival of treated patients was prolonged because of better patient selection and advancements in TACE techniques aimed at preserving liver function. At present, TACE is approved by the International Guidelines also outside of the BCLC intermediate stage after evaluation of a multidisciplinary tumor board (MDTB), permitting a customized treatment for every patient. An alternative therapeutic strategy is represented by hepatic chemoembolization with Degradable Starch Microspheres (DSM-TACE), which is based on the chemotherapeutic effect rather than on the ischemic damage to the liver tumor, requiring multiple cycles of treatment. The higher safety profile of DSM-TACE has broadened the indications to patients waiting for liver transplantation (with bridging or downstaging intention), at high risk of liver failure and ineligible for systemic therapies. This review summarises the scientific publications supporting the use of DSM-TACE and illustrates its indications depending on the disease stage from the Interventional Radiologist’s perspective.

Keywords

DSM-TACE / chemoembolization / degradable starch microspheres

References

[1] 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

[2] Raoul JL,Bolondi L,Kloeckner R.Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence.Cancer Treat Rev2019;72:28-36

[3] Reig M,Rimola J.BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update.J Hepatol2022;76:681-93 PMCID:PMC8866082

[4] Charriere B,Maulat C.Outcomes of patients with hepatocellular carcinoma are determined in multidisciplinary team meetings.J Surg Oncol2017;115:330-6

[5] Serper M,Mehta R.Association of provider specialty and multidisciplinary care with hepatocellular carcinoma treatment and mortality.Gastroenterology2017;152:1954-64 PMCID:PMC5664153

[6] Matsumoto MM,Saxena P.Comparing real world, personalized, multidisciplinary tumor board recommendations with BCLC algorithm: 321-patient analysis.Cardiovasc Intervent Radiol2021;44:1070-80

[7] Pelizzaro F,Penzo B.Transarterial chemoembolization for hepatocellular carcinoma in clinical practice: temporal trends and survival outcomes of an iterative treatment.Front Oncol2022;12:822507 PMCID:PMC8841805

[8] Kudo M,Ye SL.A changing paradigm for the treatment of intermediate-stage hepatocellular carcinoma: asia-pacific primary liver cancer expert consensus statements.Liver Cancer2020;9:245-60

[9] Puppala S.Technical update on transcatheter arterial chemoembolization.Hepatoma Res2019;2019

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

[11] Forsberg JO.Transient blood flow reduction induced by intra-arterial injection of degradable starch microspheres. Experiments on rats.Acta Chirurgica Scandinavica1978;144:275-281

[12] Yamada R,Nakamura K.Super-selective arterial embolization in unresectable hepatomas (author’s transl).Nihon Igaku Hoshasen Gakkai zasshi1979;39:540-3

[13] Taguchi T.Chemo-occlusion for the treatment of liver cancer. A new technique using degradable starch microspheres.Clin Pharmacokinet1994;26:275-91

[14] Kirchhoff TD,Layer G.Chemoocclusion vs. chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.Eur J Surg Oncol2006;32:201-7

[15] Pieper CC,Vollmar B,Schild HH.Temporary arterial embolization of liver parenchyma with degradable starch microspheres (EmboCept®S) in a swine model.Cardiovasc Intervent Radiol2015;38:435-41

[16] Ebert M,Berger G.Intravital microscopic research of microembolization with degradable starch microspheres.J Drug Deliv2013;2013:242060 PMCID:PMC3845399

[17] Håkansson L,Morales O,Warfving T.Spherex (degradable starch microspheres) chemo-occlusion-enhancement of tumor drug concentration and therapeutic efficacy: an overview.Semin Oncol1997;24:S6-100

[18] Cappelli A,Golfieri R.Transarterial radioembolization using yttrium-90 microspheres in the treatment of hepatocellular carcinoma: a review on clinical utility and developments.J Hepatocell Carcinoma2014;1:163-82 PMCID:PMC4918277

[19] Liapi E.Intra-arterial therapies for hepatocellular carcinoma: where do we stand?.Ann Surg Oncol2010;17:1234-46

[20] Aronsen KF,Holmberg J,Teder H.Controlled blocking of hepatic artery flow with enzymatically degradable microspheres combined with oncolytic drugs.Eur Surg Res1979;11:99-106

[21] Wiggermann P,Heibl M.Dynamic evaluation and quantification of microvascularization during degradable starch microspheres transarterial Chemoembolisation (DSM-TACE) of HCC lesions using contrast enhanced ultrasound (CEUS): a feasibility study.Clin Hemorheol Microcirc2013;53:337-48

[22] Yamasaki T,Harima Y.Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma.J Gastroenterol2012;47:715-22

[23] Gruber-Rouh T,Naguib NNN.Transarterial chemoembolization (TACE) using mitomycin and lipiodol with or without degradable starch microspheres for hepatocellular carcinoma: comparative study.BMC Cancer2018;18:188 PMCID:PMC5813391

[24] Vogl TJ,Hammerstingl R,Chatterjee AR.Evaluation of two different transarterial chemoembolization protocols using Lipiodol and degradable starch microspheres in therapy of hepatocellular carcinoma: a prospective trial.Hepatol Int2021;15:685-94 PMCID:PMC8286929

[25] Maeda N,Moine L.Targeting and recanalization after embolization with calibrated resorbable microspheres versus hand-cut gelatin sponge particles in a porcine kidney model.J Vasc Interv Radiol2013;24:1391-8

[26] Katsumori T.The size of gelatin sponge particles: differences with preparation method.Cardiovasc Intervent Radiol2006;29:1077-83

[27] Carr BI,Bron K,Sammon J.Phase II study of Spherex (degradable starch microspheres) injected into the hepatic artery in conjunction with doxorubicin and cisplatin in the treatment of advanced-stage hepatocellular carcinoma: interim analysis.Semin Oncol1997;24:S6-97

[28] Furuse J,Satake M.Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma.Am J Clin Oncol2003;26:159-64

[29] Gross A.Transarterial chemoembolisation (TACE) with degradable starch microspheres (DSM) and anthracycline in patients with locally extensive hepatocellular carcinoma (HCC): safety and efficacy.Cardiovasc Intervent Radiol2020;43:402-10

[30] Haubold J,Wetter A.DSM-TACE of HCC: evaluation of tumor response in patients ineligible for other systemic or loco-regional therapies.Rofo2020;192:862-9

[31] Iezzi R,Rinninella E.HepatoCatt Study GroupTACE with degradable starch microspheres (DSM-TACE) as second-line treatment in HCC patients dismissing or ineligible for sorafenib.Eur Radiol2019;29:1285-92

[32] Takayasu K,Ikai I.Liver Cancer Study Group of JapanOverall survival after transarterial lipiodol infusion chemotherapy with or without embolization for unresectable hepatocellular carcinoma: propensity score analysis.AJR Am J Roentgenol2010;194:830-7

[33] Yamasaki T,Saeki I.A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial.J Gastroenterol2011;46:359-66

[34] Idée JM.Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review.Crit Rev Oncol Hematol2013;88:530-49

[35] Renzulli M,Vasuri F.Standardization of conventional chemoembolization for hepatocellular carcinoma.Ann Hepatol2021;22:100278

[36] Kim DY,Choi JY.Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma.Aliment Pharmacol Ther2012;35:1343-50

[37] Kim S,Lee SL,Won YD.Lipiodol pneumonitis following transcatheter arterial chemoembolization for hepatocellular carcinoma.J Liver Cancer2020;20:60-6

[38] Burroughs A,Meyer T.Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum.Lancet Oncol2004;5:409-18

[39] Marelli L,Triantos C.Transarterial therapy for hepatocellular carcinoma: which technique is more effective?.Cardiovasc Intervent Radiol2007;30:6-25

[40] Jordan O,De Baere T,Doelker E.Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan.J Vasc Interv Radiol2010;21:1084-90

[41] Namur J,Millot JM,Manfait M.Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model.J Vasc Interv Radiol2010;21:259-67

[42] Ha BY,Sze DY.Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion.Aliment Pharmacol Ther2007;26:839-46

[43] Daniels JR.Subselective intra-arterial chemotherapy infusion in the treatment of hepatocellular carcinoma.Semin Oncol2010;37:83-8

[44] Kim JH,Kim SY.Transcatheter arterial chemoembolization vs. chemoinfusion for unresectable hepatocellular carcinoma in patients with major portal vein thrombosis.Aliment Pharmacol Ther2009;29:1291-8

[45] Schicho A,Krüger K.Impact of different embolic agents for transarterial chemoembolization (TACE) procedures on systemic vascular endothelial growth factor (VEGF) levels.J Clin Transl Hepatol2016;4:288-92 PMCID:PMC5225147

[46] Sergio A,Cardin R.Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness.Am J Gastroenterol2008;103:914-21

[47] Chegai F,Merolla S,Mannelli L.Intermediate hepatocellular carcinoma: the role of transarterial therapy.Hepat Oncol2015;2:399-408 PMCID:PMC4792112

[48] Brown KT,Gonen M.Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone.J Clin Oncol2016;34:2046-53 PMCID:PMC4966514

[49] Ludwig JM,Theysohn JM,Posa A.European multicenter study on degradable starch microsphere TACE: the digestible way to conquer HCC in patients with high tumor burden.Cancers (Basel)2021;13:5122 PMCID:PMC8533832

[50] Dettmer A,Gebel M.Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma.World J Gastroenterol2006;12:3707-15 PMCID:PMC4087463

[51] Kirchhoff TD,Dettmer A.Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival.Hepatobiliary Pancreat Dis Int2007;6:259-66

[52] Murata S,Ichikawa K.Oily chemoembolization combined with degradable starch microspheres for HCC with cirrhosis.Hepatogastroenterology2008;55:1041-6

[53] Schicho A,Haimerl M.Transarterial chemoembolization (TACE) with degradable starch microspheres (DSM) in hepatocellular carcinoma (HCC): multi-center results on safety and efficacy.Oncotarget2017;8:72613-20 PMCID:PMC5641156

[54] Orlacchio A,Roma S,Bosa A.Degradable starch microspheres transarterial chemoembolization (DSMs-TACE) in patients with unresectable hepatocellular carcinoma (HCC): long-term results from a single-center 137-patient cohort prospective study.Radiol Med2020;125:98-106

[55] Yildiz I,Ozer A.Trans-arterial chemoembolization with 50 μm degradable starch microspheres versus 300-500 μm drug eluting beads in Hepatocellular carcinoma: a comparative analysis of initial treatment outcomes.J Belg Soc Radiol2022;106:10 PMCID:PMC8916059

[56] Minici R,Manti F.Safety and efficacy of degradable starch microspheres transcatheter arterial chemoembolization as a bridging therapy in patients with early stage hepatocellular carcinoma and child-pugh stage B eligible for liver transplant.Front Pharmacol2021;12:634084 PMCID:PMC8062923

[57] Mohr I,Pfeiffenberger J.Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma.J Cancer Res Clin Oncol2022;148:3163-74 PMCID:PMC9508038

[58] Minici R,Manti F.Safety and efficacy of degradable starch microspheres transcatheter arterial chemoembolization (DSM-TACE) in the downstaging of intermediate-stage hepatocellular carcinoma (HCC) in patients with a child-pugh score of 8-9.Front Pharmacol2021;12:634087 PMCID:PMC8060654

[59] Niessen C,Goessmann H.Degradable starch microspheres versus ethiodol and doxorubicin in transarterial chemoembolization of hepatocellular carcinoma.J Vasc Interv Radiol2014;25:240-7

[60] Auer TA,Collettini F.Trans-arterial chemoembolization with degradable starch microspheres (DSM-TACE) versus selective internal radiation therapy (SIRT) in multifocal hepatocellular carcinoma.Acta Radiol2021;62:313-21

[61] Vincenzi B,Silletta M.Prognostic relevance of objective response according to EASL criteria and mRECIST criteria in hepatocellular carcinoma patients treated with loco-regional therapies: a literature-based meta-analysis.PLoS One2015;10:e0133488 PMCID:PMC4521926

[62] Chang WC,Chiu SH.Transcatheter arterial chemoembolization with drug-eluting beads for the treatment of hepatocellular carcinoma: recommended selection for small-caliber (< 100 μm) beads.J Hepatocell Carcinoma2021;8:937-49 PMCID:PMC8373306

[63] Lee IJ,Lee YB.Effectiveness of drug-eluting bead transarterial chemoembolization versus conventional transarterial chemoembolization for small hepatocellular carcinoma in Child-Pugh class A patients.Ther Adv Med Oncol2019;11:1758835919866072 PMCID:PMC6689910

[64] Llovet JM,Mazzaferro V.SHARP Investigators Study GroupSorafenib in advanced hepatocellular carcinoma.N Engl J Med2008;359:378-90

[65] Kalva SP,Yeddula K,Blaszkowsky LS.Factors affecting survival following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma.J Vasc Interv Radiol2013;24:257-65

[66] Zhang Y,Chen M.Association of sustained response duration with survival after conventional transarterial chemoembolization in patients with hepatocellular carcinoma.JAMA Netw Open2018;1:e183213 PMCID:PMC6324454

[67] Granito A,Sacco R.TRANS-TACE: prognostic role of the transient hypertransaminasemia after conventional chemoembolization for hepatocellular carcinoma.J Pers Med2021;11:1041 PMCID:PMC8539564

[68] Lammer J,Vogl T.PRECISION V InvestigatorsProspective 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

[69] Guiu B,Aho S.Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads.J Hepatol2012;56:609-17

[70] Woo S,Hur S.Liver abscess after transarterial chemoembolization in patients with bilioenteric anastomosis: frequency and risk factors.AJR Am J Roentgenol2013;200:1370-7

[71] Spina JC,Yeyati EL.MDCT findings after hepatic chemoembolization with DC-beads: what the radiologist needs to know.Abdom Imaging2013;38:778-84

[72] Dhamija E,Gamanagatti SR.Biliary complications of arterial chemoembolization of hepatocellular carcinoma.Diagn Interv Imaging2015;96:1169-75

[73] Salgia R.The Multidisciplinary Management of Hepatocellular Carcinoma.Clin Liver Dis (Hoboken)2021;17:405-8 PMCID:PMC8340356

[74] Gadsden MM.Multidisciplinary approach to HCC management: how can this be done?.Dig Dis Sci2019;64:968-75

[75] Zhang Y,Czeyda-Pommersheim F.Assessing the impact of referral on multidisciplinary tumor board outcomes in patients with hepatocellular carcinoma.J Am Coll Radiol2020;17:1636-43

[76] Vitale A,Farinati F.Treatment of hepatocellular carcinoma in the precision medicine era: from treatment stage migration to therapeutic hierarchy.Hepatology2020;72:2206-18

[77] Leoni S,Serio I.Adherence to AASLD guidelines for the treatment of hepatocellular carcinoma in clinical practice: experience of the Bologna Liver Oncology Group.Dig Liver Dis2014;46:549-55

[78] Jogi S,Bantu SS.Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines.Oncol Rev2020;14:515 PMCID:PMC7771021

[79] Sangiovanni A,Iavarone M.Multimodality treatment of hepatocellular carcinoma: How field practice complies with international recommendations.Liver Int2018;38:1624-34

[80] Dionisi F,Siniscalchi B.Clinical results of active scanning proton therapy for primary liver tumors.Tumori2021;107:71-9

[81] Colliez F,Jordan BF.Assessing tumor oxygenation for predicting outcome in radiation oncology: a review of studies correlating tumor hypoxic status and outcome in the preclinical and clinical settings.Front Oncol2017;7:10 PMCID:PMC5263142

[82] Kennedy AS.Nonsurgical treatment for localized hepatocellular carcinoma.Curr Oncol Rep2014;16:373 PMCID:PMC3921451

[83] Akateh C,Conteh L.Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma.World J Gastroenterol2019;25:3704-21 PMCID:PMC6676544

[84] Lei J,Yan L.Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.Sci Rep2017;7:41624

[85] Qi X,Wang D,Su C.Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: a systematic review and meta-analysis.Oncotarget2015;6:36838-59 PMCID:PMC4742214

[86] Tsutsui R,Itano O.Neoadjuvant hepatic arterial infusion chemotherapy for resectable hepatocellular carcinomas.Hepatoma Res2018;4:13

[87] Chen QW,Gao S.Radiofrequency ablation plus chemoembolization versus radiofrequency ablation alone for hepatocellular carcinoma: a systematic review and meta-analysis.Clin Res Hepatol Gastroenterol2016;40:309-14

[88] Jacob R,Redden DT.Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥ 3 cm.HPB (Oxford)2015;17:140-9 PMCID:PMC4299388

[89] Kudo M,Ikeda M.TACTICS study groupRandomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial.Gut2020;69:1492-501 PMCID:PMC7398460

[90] Ogasawara S,Koroki K.Switching to systemic therapy after locoregional treatment failure: definition and best timing.Clin Mol Hepatol2020;26:155-62 PMCID:PMC7160341

[91] Vogel A.ESMO Guidelines CommitteeElectronic address: [e-mail], ESMO Guidelines Committee. Updated treatment recommendations for hepatocellular carcinoma (HCC) from the ESMO Clinical Practice Guidelines.Ann Oncol2021;32:801-5

[92] Lucatelli P.2022 Update of BCLC treatment algorithm of HCC: what’s new for interventional radiologists?.Cardiovasc Intervent Radiol2022;45:275-6