Results of Application of Saturable Microspheres of Domestic Production in Locoregional Endovascular Treatment of Inoperable Patients with Malignant Liver Tumors

The incidence of malignant liver tumors is steadily increasing. Most patients are considered inoperable at the time of detection of a malignant liver lesion. In general, unsatisfactory liver function, comorbidities, bilobar lesion, extrahepatic metastasis allow performing radical treatment in not more than 20 % of cases. Thus, the majority of patients are indicated for other types of treatment, including endovascular locoregional techniques. Taking into account the implementation of the federal program for state support of import substitution in Russia, the creation and production of competitive products in the field of medicine, including for endovascular surgery, becomes relevant. The aim of this article was to study the properties, tolerability and safety of domestically produced saturable microspheres and evaluate the immediate results of transarterial chemoembolization in the treatment of inoperable patients with primary and metastatic liver cancer. Within the framework of the State Scientific Program, clinical studies on the use of saturable microspheres produced in Russia were conducted. The results of treatment of 32 patients who underwent transarterial chemoembolization (TACE) with the use of domestic microspheres “Sphere-Spectrum” at the N.N. Blokhin Research Institute of Oncology from January 2020 to October 2022 were analyzed. Of these, TACE was performed in 24 patients diagnosed with HCC, 5 patients with liver metastases of neuroendocrine tumors, and 3 patients with melanoma metastases. TACE was performed using microspheres with sizes 35–40 in dry (210–240 μm in saturated) 50–60 μm in dry (300–360 μm in saturated), 25 mg or 50 mg in one vial. A total of 40 endovascular procedures were performed in all 32 patients with malignant liver tumor lesions. In 11 of them (34.3 %) a single TACE session was sufficient to achieve an objective response. Partial response was observed in 21 (65.7 %) patients, including those with bilobar metastatic liver lesion. All patients tolerated treatment satisfactorily, the desired therapeutic effect was achieved in 26 (81.2 %) cases (taking into account repeated interventions). One patient (3.1 %) diagnosed with HCC had a complication in the form of liver abscess formation.

1. Bray F, Ferlay J, Soerjomataram I, et al. 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. DOI:10.3322/caac.21492.

2. 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(4):908-43. DOI:10.1016/j.jhep.2011.12.001.

3. Boland P, Wu J. Systemic therapy for hepatocellular carcinoma: beyond sorafenib. Chin Clin Oncol. 2018;7(5):50. DOI:10.21037/cco.2018.10.10.

4. Zou JH, Zhang L, Ren ZG, Ye SL. Efficacy and safety of cTACE versus DEB-TACE in patients with hepatocellular carcinoma: a meta-analysis. J Dig Dis. 2016 Aug;17(8):510-7. DOI:10.1111/1751-2980.12380.

5. Huppert P. Current concepts in transarterial chemoembolization of hepatocellular carcinoma. Abdom Imaging. 2011 Dec;36(6):677-83. DOI:10.1007/s00261-011-9755-4.

6. Lencioni R, de Baere T, Soulen MC, et al. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016 Jul;64(1):106-16. DOI:10.1002/hep.28453.

7. Vogl J. Gruber-Rouh T. HCC: Transarterial Therapies — What the Interventional Radiologist Can Offer. Dig Dis Sci. 2019 Apr;64(4):959-67. DOI:10.1007/s10620-019-05542-5/

8. Craig P, Young S, Golzarian J. Current Trends in the Treatment of Hepatocellular Carcinoma with Transarterial Embolization: Variability in Technical Aspects. Cardiovasc Intervent Radiol. 2019 Sep;42(9):1322-8. DOI:10.1007/s00270-019-02232-7.

9. Kishore SA, Bajwa R, Madoff DC. Embolotherapeutic Strategies for Hepatocellular Carcinoma: 2020 Update. Cancers (Basel). 2020 Mar 26;12(4):791. DOI:10.3390/cancers12040791.

10. Saini A, Wallace A, Alzubaidi S, et al. History and Evolution of Yttrium-90 Radioembolization for Hepatocellular Carcinoma. J Clin Med. 2019 Jan 7;8(1):55. DOI:10.3390/jcm8010055.

11. Lucatelli P, Burrel M, Guiu B, et al. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Interv Radiol. 2021 Dec;44(12):1851-67. DOI:10.1007/s00270-021-02968-1.

12. Lee IC, Huo TI, Huang YH, et al. Transarterial chemoembolization can prolong survival for patients with metastatic hepatocellular carcinoma: a propensity score matching analysis. Hepatol Int. 2012 Oct;6(4):753-62. DOI:10.1007/s12072-011-9322-7.

13. Wege H, Li J, Ittrich H. Treatment Lines in Hepatocellular Carcinoma. Visc Med. 2019 Aug;35(4):266-272. DOI:10.1159/000501749.

14. European Association for Study of Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012 Mar;48(5):599-641. DOI:10.1016/j.ejca.2011.12.021.

15. Bargellini I, Florio F, Golfieri R, et al. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol. 2014 Apr;37(2):438-44. DOI:10.1007/s00270-013-0656-5.

16. Polekhin AS, Tarazov PG, Polikarpov AA, Granov DA. Transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma on advanced liver cirrhosis. I.I. Grekov’s Bulletin of Surgery. 2019;178(6):29-35. (In Russian). DOI:10.24884/0042-4625-2019-178-6-29-35.

17. Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681-93. DOI:10.1016/j.jhep.2021.11.018.

18. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. DOI:10.1016/j.jhep.2018.03.019.

19. National Guide “Interventional Radiology in Oncology”. Ed. by B.I. Dolgushin. Moscow. 2022; Vol. 3. Chapter 5. P. 541-68. (In Russian).

20. Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007 Mar;46(3):474-81. DOI:10.1016/j.jhep.2006.10.020.

21. Malagari K, Pomoni M, Moschouris H, et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Interv Radiol. 2012 Oct;35(5):1119-28. DOI:10.1007/s00270-012-0394-0.

22. Dolgushin BI, Patutko YI, Wirschke ER, et al. Arterial chemoembolization microspheres with doxorubicin (DC BEAD™) in the treatment of patients with hepatocellular cancer (preliminary results): Annals of Surgical Hepatology. 2009;14(2):53-8. (In Russian).

23. Dolgushin BI, Wirschke ER, Kuchinsky GA, et al. X-ray endovascular treatment of inoperable hepatocellular cancer patients: Annals of Surgical Hepatology. 2010;15(4):18-23. (In Russian).

24. Dolgushin BI, Wirschke ER, Kosyrev VY, et al. Transarterial chemoembolization with doxorubicine microspheres in the treatment of inoperable hepatocellular cancer patients (distant results). Annals of Surgical Hepatology. 2013;18(4):10-6. (In Russian).

25. Komov DV, Roshchin EM, Gurtovaya IB. Drug treatment of primary and metastatic liver cancer. Moscow. 2002. (In Russian).

26. Agarwala SS, Panikkar R, Kirkwood JM. Phase I/II randomized trial of intrahepatic arterial infusion chemotherapy with cisplatin and chemoembolization with cisplatin and polyvinyl sponge in patients with ocular melanoma metastatic to the liver. Melanoma Res. 2004 Jun;14(3):217-22. DOI:10.1097/01.cmr.0000129377.22141.ea.

27. Gupta S, Yao JC, Ahrar K, et al. Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson Hospital experience. Cancer J. 2003 Jul-Aug;9(4):261-7. DOI:10.1097/00130404-200307000-00008.

28. Egger ME, Armstrong E, Martin RC 2nd, et al. Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis. J Am Coll Surg. 2020 Apr;230(4):363-70. DOI:10.1016/j.jamcollsurg.2019.12.026.

29. Jia Z, Tu J, Cao C, et al. Liver abscess following transarterial chemoembolization for the treatment of hepatocellular carcinoma: A retrospective analysis of 23 cases. J Cancer Res Ther. 2018 Sep;14(Suppl.):S628-S633. DOI:10.4103/0973-1482.199385.

30. Woo S, Chung JW, Hur S, et al. Liver abscess after transarterial chemoembolization in patients with bilioenteric anastomosis: frequency and risk factors. Am J Roentgenol. 2013 Jun;200(6):1370-7. DOI:10.2214/AJR.12.9630.

31. Nicolini D, Svegliati-Baroni G, Candelari R, et al. Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation. World J Gastroenterol. 2013 Sep 14;19(34):5622-32. DOI:10.3748/wjg.v19.i34.5622.