Skip to main content
SpringerLink
Log in

Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety

  • Clinical Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC).

Materials and Methods

We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan–Meier curves, while Cox analysis was used to identify factors affecting the prognosis.

Results

The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0 months and 8.0 months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient.

Conclusions

DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AEs:

Adverse events

CB:

CalliSphere bead

CI:

Confidence interval

CR:

Complete response

CT:

Computed tomography

C-TACE:

Conventional TACE

DCR:

Disease control rate

DEB-TACE:

Drug-eluting bead TACE

ECOG:

Eastern cooperative oncology group

HR:

Hazard ratio

ICC:

Intrahepatic cholangiocarcinoma

MRI:

Magnetic resonance imaging

mRECIST:

Modified response evaluation criteria in solid tumors

ORR:

Objective response rate

OS:

Overall survival

PFS:

Progression-free survival

PR:

Partial response

SD:

Stable disease

References

  1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–79.

    Article  Google Scholar 

  2. Gupta A, Dixon E. Epidemiology and risk factors: intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr. 2017;6(2):101–4.

    Article  Google Scholar 

  3. Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557–88.

    Article  Google Scholar 

  4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  5. Choi S-B, Kim K-S, Choi J-Y, et al. The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol. 2009;16(11):3048–56.

    Article  Google Scholar 

  6. Aljiffry M, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990–2009. World J Gastroenterol. 2009;15(34):4240–62.

    Article  CAS  Google Scholar 

  7. Kim RD, McDonough S, El-Khoueiry AB, et al. Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer. Eur J Cancer. 2020;130:219–27.

    Article  CAS  Google Scholar 

  8. Markussen A, Jensen LH, Diness LV, Larsen FO. Treatment of patients with advanced biliary tract cancer with either oxaliplatin, gemcitabine, and capecitabine or cisplatin and gemcitabine-a randomized phase II trial. Cancers. 2020; 12(7)

  9. Mazzaferro V, Gorgen A, Roayaie S, Droz Dit Busset M, Sapisochin G. Liver resection and transplantation for intrahepatic cholangiocarcinoma. J Hepatol. 2020;72(2):364–77.

    Article  Google Scholar 

  10. Hu L-S, Zhang X-F, Weiss M, et al. Recurrence patterns and timing courses following curative-intent resection for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2019;26(8):2549–57.

    Article  Google Scholar 

  11. Wang M-L, Ke Z-Y, Yin S, Liu C-H, Huang Q. The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: a meta-analysis and systematic review. Hepatobiliary Pancreat Dis Int. 2019;18(2):110–6.

    Article  Google Scholar 

  12. Tan E, Cao B, Kim J, et al. Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers. Cancer. 2021;127(8):1293–300.

    Article  CAS  Google Scholar 

  13. Chiang N, Chen M, Yang S, et al. Multicentre, phase II study of gemcitabine and S-1 in patients with advanced biliary tract cancer: TG1308 study. Liver Int. 2020;40(10):2535–43.

    Article  CAS  Google Scholar 

  14. Chen Q, Sun Y, Dai H, Guo P, Hou S, Sha X. Assessment of irinotecan loading and releasing profiles of a novel drug-eluting microsphere (CalliSpheres). Cancer Biother Radiopharm. 2020;

  15. Liu S, Yu G, Wang Q, et al. CalliSpheres microspheres drug-eluting bead transhepatic artery chemoembolization with or without sorafenib for the treatment of large liver cancer: a multi-center retrospective study. Am J Transl Res. 2021;13(12):13931–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang X, Zhou J, Zhu DD, et al. CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study. Clin Transl Oncol. 2019;21(2):167–77.

    Article  CAS  Google Scholar 

  17. Venturini M, Sallemi C, Agostini G, et al. Chemoembolization with drug eluting beads preloaded with irinotecan (DEBIRI) vs doxorubicin (DEBDOX) as a second line treatment for liver metastases from cholangiocarcinoma: a preliminary study. Br J Radiol. 2016;89(1067):20160247.

    Article  Google Scholar 

  18. Martin RCG, Howard J, Tomalty D, et al. Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry. Cardiovasc Intervent Radiol. 2010;33(5):960–6.

    Article  CAS  Google Scholar 

  19. Zhou T-Y, Zhou G-H, Zhang Y-L, et al. Drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres for treatment of unresectable intrahepatic cholangiocarcinoma. J Cancer. 2020;11(15):4534–41.

    Article  CAS  Google Scholar 

  20. Pereira PL, Iezzi R, Manfredi R, et al. The CIREL cohort: a prospective controlled registry studying the real-life use of irinotecan-loaded chemoembolisation in colorectal cancer liver metastases: interim analysis. Cardiovasc Intervent Radiol. 2021;44(1):50–62.

    Article  Google Scholar 

  21. Lencioni R. New data supporting modified RECIST (mRECIST) for hepatocellular Carcinoma. Clin Cancer Res. 2013;19(6):1312–4.

    Article  Google Scholar 

  22. Filippiadis DK, Binkert C, Pellerin O, Hoffmann RT, Krajina A, Pereira PL. Cirse quality assurance document and standards for classification of complications: the cirse classification system. Cardiovasc Intervent Radiol. 2017;40(8):1141–6.

    Article  CAS  Google Scholar 

  23. Savic LJ, Chapiro J, Geschwind J-FH. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects. Hepatobiliary Surg Nutr. 2017; 6(1)

  24. Kuhlmann JB, Euringer W, Spangenberg HC, et al. Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy. Eur J Gastroenterol Hepatol. 2012;24(4):437–43.

    CAS  PubMed  Google Scholar 

  25. Peng Z, Cao G, Hou Q, et al. The comprehensive analysis of efficacy and safety of callispheres drug-eluting beads transarterial chemoembolization in 367 liver cancer patients: a multiple-center. Cohort Study Oncol Res. 2020;28(3):249–71.

    Article  Google Scholar 

  26. Laurent A, Wassef M, Chapot R, et al. Partition of calibrated tris-acryl gelatin microspheres in the arterial vasculature of embolized nasopharyngeal angiofibromas and paragangliomas. J Vasc Interv Radiol. 2005;16(4):507–13.

    Article  Google Scholar 

  27. Lee K-H, Liapi E, Ventura VP, et al. Evaluation of different calibrated spherical polyvinyl alcohol microspheres in transcatheter arterial chemoembolization: VX2 tumor model in rabbit liver. J Vasc Interv Radiol. 2008;19(7):1065–9.

    Article  Google Scholar 

  28. Lee K-H, Liapi E, Vossen JA, et al. Distribution of iron oxide-containing embosphere particles after transcatheter arterial embolization in an animal model of liver cancer: evaluation with MR imaging and implication for therapy. J Vasc Interv Radiol. 2008;19(10):1490–6.

    Article  Google Scholar 

  29. Zhang S, Huang C, Li Z, et al. Comparison of pharmacokinetics and drug release in tissues after transarterial chemoembolization with doxorubicin using diverse lipiodol emulsions and CalliSpheres Beads in rabbit livers. Drug Deliv. 2017;24(1):1011–7.

    Article  Google Scholar 

  30. Marquardt S, Kirstein MM, Brüning R, et al. Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: european multicentre study on safety, short-term effects and survival. Eur Radiol. 2019;29(4):1882–92.

    Article  Google Scholar 

  31. Sohal D, Mykulowycz K, Uehara T, et al. A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Ann Oncol. 2013;24(12):3061–5.

    Article  CAS  Google Scholar 

  32. Higashi M, Yamada N, Yokoyama S, et al. Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. Pathobiology. 2012;79(2):101–6.

    Article  CAS  Google Scholar 

  33. Mosconi C, Solaini L, Vara G, et al. Transarterial chemoembolization and radioembolization for unresectable intrahepatic cholangiocarcinoma-a systemic review and meta-analysis. Cardiovasc Intervent Radiol. 2021;44(5):728–38.

    Article  Google Scholar 

  34. Bagante F, Spolverato G, Merath K, et al. Intrahepatic cholangiocarcinoma tumor burden: a classification and regression tree model to define prognostic groups after resection. Surgery. 2019;166(6):983–90.

    Article  Google Scholar 

  35. Asaoka T, Kobayashi S, Hanaki T, et al. Clinical significance of preoperative CA19-9 and lymph node metastasis in intrahepatic cholangiocarcinoma. Surg Today. 2020;50(10):1176–86.

    Article  Google Scholar 

  36. Woo S, Chung JW, Hur S, et al. Liver abscess after transarterial chemoembolization in patients with bilioenteric anastomosis: frequency and risk factors. AJR Am J Roentgenol. 2013;200(6):1370–7.

    Article  Google Scholar 

  37. Schicho A, Pereira PL, Pützler M, et al. Degradable starch microspheres transcatheter arterial chemoembolization (DSM-TACE) in intrahepatic cholangiocellular carcinoma (ICC): results from a national multi-center study on safety and efficacy. Med Sci Monit. 2017;23:796–800.

    Article  CAS  Google Scholar 

  38. Carter S, Martin Ii RCG. Drug-eluting bead therapy in primary and metastatic disease of the liver. HPB. 2009;11(7):541–50.

    Article  Google Scholar 

  39. Aliberti C, Benea G, Tilli M, Fiorentini G. Chemoembolization (TACE) of unresectable intrahepatic cholangiocarcinoma with slow-release doxorubicin-eluting beads: preliminary results. Cardiovasc Intervent Radiol. 2008;31(5):883–8.

    Article  Google Scholar 

  40. Poggi G, Quaretti P, Minoia C, et al. Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres (OEM-TACE) for unresectable hepatic tumors. Anticancer Res. 2008;28:3835–42.

    CAS  PubMed  Google Scholar 

  41. Tsilimigras DI, Sahara K, Wu L, et al. Very early recurrence after liver resection for intrahepatic cholangiocarcinoma: considering alternative treatment approaches. JAMA Surg. 2020;155(9):823–31.

    Article  Google Scholar 

  42. Goyal L, Sirard C, Schrag M, et al. Phase I and biomarker study of the Wnt pathway modulator DKN-01 in combination with gemcitabine/cisplatin in advanced biliary tract cancer. Clin Cancer Res. 2020;26(23):6158–67.

    Article  CAS  Google Scholar 

  43. Colyn L, Bárcena-Varela M, Álvarez-Sola G, et al. Dual targeting of G9a and DNMT1 for the treatment of experimental cholangiocarcinoma. Hepatology. 2020;

  44. Meadows V, Francis H. Doublecortin-like kinase protein 1 in cholangiocarcinoma: is this the biomarker and target we have been looking for? Hepatology. 2021;73(1):4–6.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by grants from the Research Fund for Interventional Oncology of Beijing Medical Award Foundation (No. XM2018_011_0006_01) and Capital's Funds for Health Improvement and Research (NO. Z181100001718075).

Author information

Author notes

  1. Dong Liu and Junxiao Wang have contributed equally to this article.

Authors and Affiliations

  1. Department of Radiology, The First Hospital of Tsinghua University, Beijing, 100016, China

    Dong Liu

  2. Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China

    Junxiao Wang, Zhenhu Ma, Yun Zhao, Xiang Yang, Zhenyu Wen & Hui Xie

  3. Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, Jilin, 130000, China

    Junxiao Wang & Zhenyu Wen

  4. Department of Liver Disease, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China

    Ning Zhang

Authors
  1. Dong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junxiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenhu Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ning Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhenyu Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hui Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XH: Conceptualization, substantial contributions to conception, formulation or evolution of overarching research goals and aims. LD, WJ: Methodology and Writing- original draft preparation, substantial contributions to Development of methodology and original draft preparation. MZ, ZN, ZY: Resources and Methodology, substantial contributions to samples collection, acquisition of data and analysis. YX, WZ: Investigation, substantial contributions to investigation process, specifically performing the experiments and data collection.

Corresponding author

Correspondence to Hui Xie.

Ethics declarations

Conflict of interest

The authors have no competing interests to declare.

Ethical Approval

The study was approved by the ethics committee, and each patient and guardian provided informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, D., Wang, J., Ma, Z. et al. Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety. Cardiovasc Intervent Radiol 45, 1092–1101 (2022). https://doi.org/10.1007/s00270-022-03108-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-022-03108-z

Keywords

Search

Navigation