Liver Radioembolization: a New Chapter in Russian Oncology

Recent years have seen an increase in the number of patients with malignant tumours of the liver. In this context, new treatment methods are being actively introduced into practice, one of which is liver radioembolization utilizing microspheres embedded with yttrium-90 (⁹⁰Y).

Aim. To review literature data on the history of radioembolization and its application for liver tumours.

Key findings. Annually, over 200 thousand patients with inoperable primary liver cancer and over 270 thousand patients with inoperable metastatic liver cancer are registered globally, for whom radioembolization is considered as the most suitable treatment method. ⁹⁰Y is a pure beta emitter without its own gamma line, which is characterized by a small average particle path in the tissue of 2.5 mm (the maximum level is 11 mm), a maximum beta particle energy of 2.27 MeV (average energy of 0.937 MeV) and a half-life of 64.1 hours. Clinical research into microspheres containing ⁹⁰Y has been actively conducted since 1977 all over the world. However, it was only in 2004 that the US FDA authorized the clinical use of glass microspheres containing ⁹⁰Y for the treatment of hepatocellular cancer and liver colorectal cancer metastases. Until recently, radioembolization has not been applied in Russia. In 2018, the joint efforts of the A. Tsyb Medical Radiological Research Centre (MRRC) — branch of the National Medical Research Radiological Centre and BEBIG LLC resulted in the production of Russian microspheres containing yttrium-90, which were subsequently introduced into routine clinical practice. The first liver embolization in Russia using microspheres containing domestic yttrium-90 (BEBIG LLC) to a patient with hepatocellular cancer was carried out by V.V. Kucherov and A.P. Petrosyan at the A. Tsyb RMMC on April, 25 in 2019.

Conclusion. The production of microspheres containing ⁹⁰Y in Russia, as well as a technical improvement of the procedure, will facilitate the introduction of liver radioembolization into the routine management of patients with malignant liver tumours.

1. Состояние онкологической помощи населению России в 2017 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018. [The status of cancer treatment for the population of Russia in 2017. Ed. A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow: MNIOI named after P.A. Gertzen — a branch of the Federal State Budgetary Institution Scientific Research Center for Radiology of the Ministry of Health of Russia, 2018 (In Rus.)].

2. Базин И.С., Бредер В.В., Виршке Э.Р., Горбунова В.А., Долгушин Б.И., Косырев В.Ю., Кукушкин А.В., Макаров Е.С., Мороз Е.А., Нечушкин М.И., Патютко Ю.И., Поляков А.Н., Сагайдак И.В., Сергеева О.Н., Файнштейн И.А. Клинические рекомендации по диагностике и лечению больных раком печени и внепеченочных желчных протоков. М.: Общероссийский союз общественных объединений, Ассоциация онкологов России, 2014. [Bazin I.S., Breder V.V., Virshke E.R., Gorbunova V.A., Dolgushin B.I., Kosyrev V.Yu., Kukushkin A.V., Makarov E.S., Moroz E.A., Nechushkin M.I., Patyutko Yu.I., Polyakov A.N., Sagaidak I.V., Sergeeva O.N., Fainstein I.A. Clinical recommendations for the diagnosis and treatment of patients with the cancer of the liver and extrahepatic bile ducts. Moscow: All-Russian Union of Public Associations, Association of Oncologists of Russia, 2014 (In Rus.)].

3. Salem R., Thurston K.G. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J. Vasc. Interv. Radiol. 2006;17:1571–93.

4. Гранов А.М., Давыдов М.И. (ред.). Интервенционная радиология в онкологии. СПб.: Фолиант, 2013. 560 с. [Granov A.M., Davydov M.I. (ed.). Interventional radiology in oncology. St. Petersburg: Foliant, 2013. 560 p. (In Rus.)].

5. Phillips R., Murikami K. Primary neoplasms of the liver: Results of radiation therapy. Cancer (Philad.). 1960;13: 714–20.

6. Asakura H. Intratumoral injection therapy with Yttrium-90 chloride colloid. Nihon Igaku Hoshasen Gakkai Zasshi. 1964;23:1493–509.

7. Raoul J.L., Guyader D., Bretagne J.F., Duvauferrier R., Bourguet P. et al. Randomized controlled trial for hepatocellular carcinoma with portal vein thrombosis: intra-arterial iodine-131-iodized oil versus medical support. J. Nucl. Med. 1994;35:1782–7.

8. Raoul J.L., Guyader D., Bretagne J.F., Heautot J.F., Duvauferrier R. et al. Prospective randomized trial of chemoembolization versus intra-arterial injection of 131Ilabeled-iodized oil in the treatment of hepatocellular carcinoma. Hepatology. 1997;26:1156–61.

9. Ariel I.M., Pack G.T. Treatment of inoperable cancer of the liver by intra-arterial radioactive isotopes and chemotherapy. Cancer (Philad.). 1967;20:793–804.

10. Grady E.D., Nolan T.R., Crumbley A.J., Rosen A.R. Internal radiation therapy of liver cancer (90-Yttrium resin spheres intraarterially) to supplement external radiation therapy, local and systemic chemotherapy. J. Med. Assoc. Ga. 1977;66(8):625–9.

11. Reinders M.T.M., Mees E., Powerski M.J. et al. Radioembolisation in Europe: A Survey Amongst CIRSE Members. Cardiovasc. Intervent. Radiol. 2018;41:1579. DOI: 10.1007/S00270-018-1982-4

12. Меркулов В.Г., Хабас Т.А., Кулинич Е.А. Радиоактивные источники медицинского назначения на основе биоинертных керамических материалов. Известия высших учебных заведений. Физика. 2010;53(10-2):329–33. [Merkulov V.G., Khabas T.A., Kulinich E.A. Radioactive medical sources based on bioinert ceramic materials. News of higher educational institutions. Physics. 2010;53(10-2):329–33 (In Rus.)].

13. Шаповалов В.В., Мельниченко Н.А., Нерозин Н.А., Ткачев С.В., Тогаева Н.Р., Хамьянов С.В. Экстракционно-хроматографическое выделение 90Y для медицинских целей. Радиохимия. 2012;54(4):357–59. [Shapovalov V.V., Melnichenko N.A., Nerozin N.A., Tkachev S.V., Togaeva N.R., Khamyanov S.V. 90Y extraction-chromatographic isolation for medical purposes. Radiochemistry. 2012;54(4):357–59 (In Rus.)].

14. Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives. Hepatology. 2013;58(6):2188–97. DOI: 10.1002/hep.26382

15. EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2018; 69:182–236.

16. Vogel A., Cervantes A., Chau I., Daniele B., Llovet J.M., Meyer T., Nault J.-C., Neumann U., Ricke J., Sangro B., Schirmacher P., Verslype C., Zech C.J., Arnold D., Martinelli E. ESMO Guidelines Committee, Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2018;29(Suppl 4):238–55. DOI: 10.1093/annonc/mdy308

17. NCCN Clinical Practice Guidelines in Oncology, Hepatobiliary Cancers. 2.2018. National Comprehensive Cancer Network. Fort Washington, PA [Update: Jun 2018; Accessed: Sep 2018].

18. Thomas M.B., Jaffe D., Choti M.M., Belghiti J., Curley S., Fong Y., Gores G., Kerlan R., Merle P., O’Neil B., Poon R., Schwartz L., Tepper J., Yao F., Haller D., Mooney M., Venook A. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J. Clin. Oncol. 2010;28(25):3994–4005.

19. Powerski M.J., Scheurig-Munkler C., Banzer J., Schnapauff D., Hamm B., Gebauer B. Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centres in Europe. Eur. J. Radiol. 2012;81(7):e804–11. DOI: 10.1016/j.ejrad.2012.04.004

20. Таразов П.Г., Поликарпов А.А., Иванова А.А. Артериальная радиоэмболизация злокачественных опухолей печени стеклянными микросферами иттрия-90: первый опыт. Диагностическая и интервенционная радиология. 2014;8:59–66. [Tarazov P.G., Polikarpov A.A., Ivanova A.A. Arterial radioembolization of malignant liver tumours with yttrium-90 glass microspheres: first experience. Diagnostic and interventional radiology. 2014;8:59–66 (In Rus.)].