Holmium-166 Radioembolization in Hepatocellular Carcinoma: Feasibility and Safety of a New Treatment Option in Clinical Practice
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To investigate clinical feasibility, technical success and toxicity of 166Ho-radioembolization (166Ho-RE) as new approach for treatment of hepatocellular carcinomas (HCC) and to assess postinterventional calculation of exact dosimetry through quantitative analysis of MR images.
Materials and Methods
From March 2017 to April 2018, nine patients suffering from HCC were treated with 166Ho-RE. To calculate mean doses on healthy liver/tumor tissue, MR was performed within the first day after treatment. For evaluation of hepatotoxicity and to rule out radioembolization-induced liver disease (REILD), the Model for End-Stage Liver Disease (MELD) Score, the Common Terminology Criteria for Adverse Events and specific laboratory parameters were used 1-day pre- and posttreatment and after 60 days. After 6 months, MR/CT follow-up was performed.
In five patients the right liver lobe, in one patient the left liver lobe and in three patients both liver lobes were treated. Median administered activity was 3.7 GBq (range 1.7–5.9 GBq). Median dose on healthy liver tissue was 41 Gy (21–55 Gy) and on tumor tissue 112 Gy (61–172 Gy). Four patients suffered from mild postradioembolization syndrome. No significant differences in median MELD-Score were observed pre-, posttherapeutic and 60 days after 166Ho-RE. No deterioration of liver function and no indicators of REILD were observed. One patient showed a complete response, four a partial response, three a stable disease and one a progressive disease at the 6 months follow-up.
166Ho-RE seems to be a feasible and safe treatment option with no significant hepatotoxicity for treatment of HCC.
KeywordsHolmium Microspheres Radioembolization SIRT Liver Hepatocellular carcinoma HCC Radioembolization-induced liver disease REILD RILD Cirrhosis
This study was not supported by any funding.
Compliance with Ethical Standards
Conflict of interest
R.-T. Hoffmann participates as proctor, advisory board member and received speaker’s honoraria from Sirtex and Terumo. The other authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by local ethics committee. In addition, it is a retrospective study, and for this type of study, formal consent is not required.
Informed consent was obtained from all individual participants included in the study.
Consent for Publication
Consent for publication was obtained for every individual person’s data included in the study.
- 1.Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, et al. The Burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol. 2017;3(12):1683–91. https://doi.org/10.1001/jamaoncol.2017.3055.CrossRefGoogle Scholar
- 4.Levi Sandri GB, Ettorre GM, Giannelli V, Colasanti M, Sciuto R, Pizzi G, et al. Trans-arterial radio-embolization: a new chance for patients with hepatocellular cancer to access liver transplantation, a world review. Transl Gastroenterol Hepatol. 2017;2:98. https://doi.org/10.21037/tgh.2017.11.11.CrossRefGoogle Scholar
- 7.Nijsen JF, Zonnenberg BA, Woittiez JR, Rook DW, Swildens-van Woudenberg IA, van Rijk PP, et al. Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques. Eur J Nucl Med. 1999;26(7):699–704.CrossRefGoogle Scholar
- 10.Vente MA, Nijsen JF, de Wit TC, Seppenwoolde JH, Krijger GC, Seevinck PR, et al. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs. Eur J Nucl Med Mol Imaging. 2008;35(7):1259–71. https://doi.org/10.1007/s00259-008-0747-8.CrossRefGoogle Scholar
- 11.Zielhuis SW, Nijsen JF, Seppenwoolde JH, Bakker CJ, Krijger GC, Dullens HF, et al. Long-term toxicity of holmium-loaded poly(l-lactic acid) microspheres in rats. Biomaterials. 2007;28(31):4591–9. https://doi.org/10.1016/j.biomaterials.2007.07.012.CrossRefGoogle Scholar
- 12.Smits ML, Elschot M, van den Bosch MA, van de Maat GH, van het Schip AD, Zonnenberg BA, et al. In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies. J Nucl Med. 2013;54(12):2093–100. https://doi.org/10.2967/jnumed.113.119768.CrossRefGoogle Scholar
- 14.Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Mali WP, et al. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012;13(10):1025–34. https://doi.org/10.1016/S1470-2045(12)70334-0.CrossRefGoogle Scholar
- 15.Salem R, Thurston KG. Radioembolization with 90-yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodologic considerations. J Vasc Interv Radiol. 2006;17(8):1251–78. https://doi.org/10.1097/01.rvi.0000233785.75257.9a.CrossRefGoogle Scholar
- 20.Seevinck PR, van de Maat GH, de Wit TC, Vente MA, Nijsen JF, Bakker CJ. Magnetic resonance imaging-based radiation-absorbed dose estimation of 166Ho microspheres in liver radioembolization. Int J Radiat Oncol Biol Phys. 2012;83(3):e437–44. https://doi.org/10.1016/j.ijrobp.2011.12.085.CrossRefGoogle Scholar
- 24.Prince JF, van den Bosch M, Nijsen JFW, Smits MLJ, van den Hoven AF, Nikolakopoulos S, et al. Efficacy of radioembolization with (166)Ho-microspheres in salvage patients with liver metastases: a phase 2 study. J Nucl Med. 2018;59(4):582–8. https://doi.org/10.2967/jnumed.117.197194.CrossRefGoogle Scholar
- 25.Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting C, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys. 2007;68(1):13–23. https://doi.org/10.1016/j.ijrobp.2006.11.060.CrossRefGoogle Scholar
- 34.Gulec SA, Mesoloras G, Dezarn WA, McNeillie P, Kennedy AS. Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: the tumor selectivity of the treatment as a function of tumor to liver flow ratio. J Transl Med. 2007;5:15. https://doi.org/10.1186/1479-5876-5-15.CrossRefGoogle Scholar
- 35.Fajardo LF, Colby TV. Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med. 1980;104(11):584–8.Google Scholar
- 38.Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S, et al. Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma. J Hepatol. 2013;59(4):753–61. https://doi.org/10.1016/j.jhep.2013.05.025.CrossRefGoogle Scholar
- 41.Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54(3):868–78. https://doi.org/10.1002/hep.24451.CrossRefGoogle Scholar
- 42.Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151(6):1155–63. https://doi.org/10.1053/j.gastro.2016.08.029.CrossRefGoogle Scholar
- 43.Mantry PS, Mehta A, Madani B, Mejia A, Shahin I. Selective internal radiation therapy using yttrium-90 resin microspheres in patients with unresectable hepatocellular carcinoma: a retrospective study. J Gastrointest Oncol. 2017;8(5):799–807. https://doi.org/10.21037/jgo.2017.08.03.CrossRefGoogle Scholar