Skip to main content
SpringerLink
Log in

Arterial Embolization Using Microspheres for Hypervascular Liver Metastases Refractory to Standard Treatments: A Multicenter Prospective Clinical Trial

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

Abstract

Purpose

To evaluate the clinical utility of bland arterial embolization using microspheres in patients with hypervascular liver metastases refractory to standard treatments.

Materials and Methods

Primary endpoints of this prospective single-arm non-comparative study were objective response and disease control rates (ORR and DCR), based on the modified Response Evaluation Criteria in Solid Tumors at 4 weeks after embolization. Secondary endpoints were ORR according to primary tumor, overall survival, progression-free survival (PFS), and safety.

Results

Twenty-five patients with a median age of 66 years (range, 40–95 years) were enrolled in this study. The median maximum diameter of liver metastasis was 3.7 cm (range, 2.0–15.2 cm). Primary lesions were colorectal cancer in 12 patients (48%, 12/25), other cancer in 7 (28%, 7/25), neuroendocrine tumor in 4 (16%, 4/25), and sarcoma in 2 (8%, 2/25). ORR and DCR were 52% (13/25) and 72% (18/25) in all patients, 42% (5/12) and 75% (9/12) in colorectal cancer patients, and 62% (8/13) and 69% (9/13) in other malignant tumor patients (p = 0.43, p > 0.99). Median survival time was 19 months in all patients, 19 months in colorectal cancer patients, and 8 months (p = 0.16) in other malignant tumor patients. Median PFS time was 4 months in all patients, 4 months in colorectal cancer patients, and 6 months (p = 0.0085) in other malignant tumor patients. There were no grade-3 or -4 adverse events.

Conclusion

Microsphere embolization appears to be an effective and safe treatment for hypervascular liver metastases refractory to standard treatments.

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

Similar content being viewed by others

References

  1. de Ridder J, de Wilt JH, Simmer F, Overbeek L, Lemmens V, Nagtegaal I. Incidence and origin of histologically confirmed liver metastases: an explorative case-study of 23,154 patients. Oncotarget. 2016;7:55368–76.

    Article  Google Scholar 

  2. Bengtsson G, Carlsson G, Hafström L, Jönsson PE. Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg. 1981;141:586–9.

    Article  CAS  Google Scholar 

  3. Ren Y, Dai C, Zheng H, et al. Prognostic effect of liver metastasis in lung cancer patients with distant metastasis. Oncotarget. 2016;7:53245–53.

    Article  Google Scholar 

  4. He X, Zhang Q, Feng Y, et al. Resection of liver metastases from breast cancer: a multicentre analysis. Clin Transl Oncol. 2020;22:512–21.

    Article  CAS  Google Scholar 

  5. Maluccio MA, Covey AM, Schubert J, et al. Treatment of metastatic sarcoma to the liver with bland embolization. Cancer. 2006;107:1617–23.

    Article  Google Scholar 

  6. Maire F, Lombard-Bohas C, O’Toole D, et al. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study. Neuroendocrinology. 2012;96:294–300.

    Article  CAS  Google Scholar 

  7. Pitt SC, Knuth J, Keily JM, et al. Hepatic neuroendocrine metastases: chemo- or bland embolization? J Gastrointest Surg. 2008;12:1951–60.

    Article  Google Scholar 

  8. Fiore F, Del Prete M, Franco R, et al. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine. 2014;47:177–82.

    Article  CAS  Google Scholar 

  9. Tanaka T, Nishiofuku H, Maeda S, et al. Repeated bland-TAE using small microspheres injected via an implantable port-catheter system for liver metastases: an initial experience. Cardiovasc Intervent Radiol. 2014;37:493–7.

    Article  Google Scholar 

  10. Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13:72–8.

    Article  Google Scholar 

  11. Ruutiainen AT, Soulen MC, Tuite CM, et al. Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol. 2007;18:847–55.

    Article  Google Scholar 

  12. Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer. 2005;104:1590–602.

    Article  Google Scholar 

  13. Laurent A. Microspheres and nonspherical particles for embolization. Tech Vasc Interv Radiol. 2007;10:248–56. https://doi.org/10.1053/j.tvir.2008.03.010.

    Article  CAS  PubMed  Google Scholar 

  14. Osuga K, Maeda N, Higashihara H, et al. Current status of embolic agents for liver tumor embolization. Int J Clin Oncol. 2012;17:306–15.

    Article  CAS  Google Scholar 

  15. Osuga K, Nakajima Y, Sone M, Arai Y, Nambu Y, Hori S. Transarterial embolization of hypervascular tumors using trisacryl gelatin microspheres (Embosphere): a prospective multicenter clinical trial in Japan. Jpn J Radiol. 2016;34:366–75.

    Article  CAS  Google Scholar 

  16. Akinduro OO, Mbabuike N, ReFaey K, et al. Microsphere embolization of hypervascular posterior fossa tumors. World Neurosurg. 2018;109:182–7.

    Article  Google Scholar 

  17. Doucet J, Kiri L, O’Connell K, et al. Advances in degradable embolic microspheres: a state of the art review. J Funct Biomater. 2018;9:14.

    Article  Google Scholar 

  18. Osuga K, Hori S, Hiraishi K, et al. Bland embolization of hepatocellular carcinoma using superabsorbent polymer microspheres. Cardiovasc Intervent Radiol. 2008;31:1108–16.

    Article  Google Scholar 

  19. Seki A, Hori S, Shimono C. Management of vascular lake phenomenon on angiography during chemoembolization with superabsorbent polymer microspheres. Jpn J Radiol. 2015;33:741–8.

    Article  CAS  Google Scholar 

  20. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.

    Article  CAS  Google Scholar 

  21. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  Google Scholar 

  22. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Washington, DC: US Department of Health and Human Services, 2010.

  23. Samaras P, Breitenstein S, Haile SR, et al. Selective intra-arterial chemotherapy with floxuridine as second- or third-line approach in patients with unresectable colorectal liver metastases. Ann Surg Oncol. 2011;18:1924–31.

    Article  Google Scholar 

  24. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.

    Article  CAS  Google Scholar 

  25. Rothenberg ML, Cox JV, Butts C, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol. 2008;19:1720–6.

    Article  CAS  Google Scholar 

  26. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381:303–12.

    Article  CAS  Google Scholar 

  27. Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16:619–29.

    Article  CAS  Google Scholar 

  28. Takaki H, Litchman T, Covey A, et al. Hepatic artery embolization for liver metastasis of gastrointestinal stromal tumor following imatinib and sunitinib therapy. J Gastrointest Cancer. 2014;45:494–9.

    Article  CAS  Google Scholar 

  29. Brown DB, Fundakowski CE, Lisker-Melman M, et al. Comparison of MELD and Child–Pugh scores to predict survival after chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 2004; 15:1209–18.

  30. Georgiades CS, Hong K, D’Angelo M, Geschwind JF. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol. 2005;16:1653–9.

    Article  Google Scholar 

  31. Mondazzi L, Bottelli R, Brambilla G, et al. Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors. Hepatology. 1994;19:1115–23.

    Article  CAS  Google Scholar 

  32. Ikeda M, Okada S, Yamamoto S, et al. Prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization. Jpn J Clin Oncol. 2002;32:455–60.

    Article  Google Scholar 

  33. White JA, Redden DT, Bryant MK, et al. Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma. HPB (Oxford). 2014;16:1095–101.

    Article  Google Scholar 

  34. Yamakado K, Miyayama S, Hirota S, et al. Hepatic arterial embolization for unresectable hepatocellular carcinomas: do technical factors affect prognosis? Jpn J Radiol. 2012;30:560–6.

    Article  Google Scholar 

  35. Pelage JP, Le Dref O, Beregi JP, et al. Limited uterine artery embolization with tris-acryl gelatin microspheres for uterine fibroids. J Vasc Interv Radiol. 2003;14:15–20.

    Article  Google Scholar 

  36. Cosimelli M, Golfieri R, Cagol PP, et al. Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer. 2010;103:324–31.

    Article  CAS  Google Scholar 

  37. Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65:412–25.

    Article  CAS  Google Scholar 

  38. Bester L, Meteling B, Pocock N, et al. Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. J Vasc Interv Radiol. 2012;23:96–105.

    Article  Google Scholar 

  39. Cianni R, Urigo C, Notarianni E, et al. Selective internal radiation therapy with SIR-spheres for the treatment of unresectable colorectal hepatic metastases. Cardiovasc Intervent Radiol. 2009;32:1179–86.

    Article  Google Scholar 

  40. Jakobs TF, Hoffmann RT, Dehm K, et al. Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. J Vasc Interv Radiol. 2008;19:1187–95.

    Article  Google Scholar 

  41. Nace GW, Steel JL, Amesur N, et al. Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience. Int J Surg Oncol. 2011;2011:571261.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

We thank the members of the study committee for response evaluation (Hiroshi Kondo, MD, Takashi Yamanaka, MD, and Atsuhiro Nakatsuka, MD), and all the investigators of this trial. This work was supported by JSPS KAKENHI (Grant Number 16K10371).

Author information

Authors and Affiliations

  1. Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Masashi Shimohira

  2. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan

    Yozo Sato & Yoshitaka Inaba

  3. Department of Interventional Radiology, Miyakojima IGRT Clinic, Osaka, 534-0021, Japan

    Taku Yasumoto

  4. Department of Radiology, Teine Keijinkai Hospital, Sapporo, 006-0811, Japan

    Yoshihisa Kodama

  5. Department of Radiology, Nara Medical University, Kashihara, 634-8521, Japan

    Tetsuya Masada

  6. Department of Radiology, Hyogo College of Medicine, Nishinomiya, 663-8501, Japan

    Koichiro Yamakado

Authors
  1. Masashi Shimohira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yozo Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taku Yasumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshihisa Kodama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tetsuya Masada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshitaka Inaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koichiro Yamakado
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masashi Shimohira.

Ethics declarations

Conflict of interest

We do not have any Conflict of Interest.

Ethical Approval

The study protocol, which was approved by the ethics committees of all institutions, was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients. This study was registered as Clinical Trials Registry no. UMIN000019848 (www.umin.ac.jp/ctr/index.htm).

Consent for Publication

Consent for publication was obtained by all authors.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimohira, M., Sato, Y., Yasumoto, T. et al. Arterial Embolization Using Microspheres for Hypervascular Liver Metastases Refractory to Standard Treatments: A Multicenter Prospective Clinical Trial. Cardiovasc Intervent Radiol 44, 392–400 (2021). https://doi.org/10.1007/s00270-020-02673-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-020-02673-5

Keywords

Search

Navigation