Understanding Liver Treatment to Improve Microsphere Optimal distribution
Dr. J.F.W. Nijsen
Dr. E. Groot Jebbink
This project is a collaboration between Radboudumc Nijmegen, University of Twente and UMC Groningen. Companies involved in this project: Quirem Medical, Terumo, Organ Assist, Femto and Siemens Healthineers.
Approximately 900,000 new cases of liver cancer are reported worldwide annually. With 830,000 deaths each year it is the third leading cause of cancer death worldwide in 2020 (1). Treatment options are limited, less than 15% of the patients are candidates for surgery and half of them for chemotherapy or radiotherapy (2). Selective Internal Radiation Therapy (SIRT), also called radioembolization, is a treatment option for patients ineligible for curative therapy (3). During radioembolization, radioactive microspheres are injected into the hepatic artery via a microcatheter. Since hepatic malignancies are mainly fed by arterial blood, the microspheres will lodge mostly in and around the tumor and deliver a high local radiation dose. (4)
Currently, three different types of radioactive microspheres are commercially available; two types of microspheres containing the radionuclide Yttrium-90 (90Y) and one newer type containing Holmium-166 (166Ho). Holmium provides an alternative to 90Y microspheres with superior characteristics for imaging. The benefit of 166Ho is that besides beta radiation it emits low-energy gamma rays, making visualization of the microspheres by Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) possible. As Holmium is a lanthanide, visualization of the microspheres with Magnetic Resonance Imaging (MRI) is also possible. (4)
Even though radioembolization is a safe treatment, uncertainty remains about the distribution of the microspheres throughout the liver (5). To try and detect which parameters influence this distribution of the microspheres, simulating the particle hemodynamics in hepatic arteries during radioembolization by computational fluid dynamics (CFD) tools has become a valuable approach. (6) Such a CFD model can help to predict where and in what concentration microspheres will deposit (7). However, up to now the results from CFD simulations have not yet been compared to the actual microsphere distribution in real patients. Therefore, the goal of this research project is to validate a CFD model by performing in vitro, ex vivo and in vivo experiments.
In this research project it will be investigated which parameters influence the microsphere distribution, using increasingly complex models to mimic the in vivo situation, starting with an in vitro hepatic vessel model and extending towards ex vivo experiments on porcine and human livers.
- Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021;71(3):209-49.
- Pleguezuelo M, Germani G, Marelli L, Xiruochakis E, Misseri M, Manousou P, et al. Evidence-based diagnosis and locoregional therapy for hepatocellular carcinoma. Expert Review of Gastroenterology & Hepatology. 2008;2(6):761-84.
- Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52(5):1741-9.
- Reinders MTM, Smits MLJ, Van Roekel C, Braat AJAT. Holmium-166 Microsphere Radioembolization of Hepatic Malignancies. Seminars in Nuclear Medicine. 2019;49(3):237-43.
- Caine M, McCafferty MS, McGhee S, Garcia P, Mullett WM, Zhang X, et al. Impact of Yttrium-90 Microsphere Density, Flow Dynamics, and Administration Technique on Spatial Distribution: Analysis Using an In Vitro Model. Journal of Vascular and Interventional Radiology. 2017;28(2):260-8.e2.
- Aramburu J, Antón R, Rivas A, Ramos JC, Sangro B, Bilbao JI. Liver Radioembolization: An Analysis of Parameters that Influence the Catheter-Based Particle-Delivery via CFD. Curr Med Chem. 2020;27(10):1600-15.
- Kennedy AS, Kleinstreuer C, Basciano CA, Dezarn WA. Computer Modeling of Yttrium-90–Microsphere Transport in the Hepatic Arterial Tree to Improve Clinical Outcomes. International Journal of Radiation Oncology*Biology*Physics. 2010;76(2):631-7.