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6 - Principles of radioembolization

from Section II - Principles of image-guided therapies

Published online by Cambridge University Press:  05 September 2016

Vanessa L. Gates
Affiliation:
Northwestern University
Riad Salem
Affiliation:
Northwestern University
Robert J. Lewandowski
Affiliation:
Northwestern University
Jean-Francois H. Geschwind
Affiliation:
Yale University School of Medicine, Connecticut
Michael C. Soulen
Affiliation:
Department of Radiology, University of Pennsylvania Hospital, Philadelphia
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Summary

Introduction

Radioembolization is defined as the administration of micron-sized embolic particles loaded with a radionuclide using percutaneous transarterial techniques. Fluoroscopic guidance, angiographic endpoints of embolization and stasis, and the need to modify this based on angiographic findings makes this treatment a true embolization procedure. Dosimetry planning, the administration and delivery of radiation on the microscopic level, the modification of the dose based on tumor and hepatic volume, in addition to the required knowledge of radiation effects on tissue make this a brachytherapy procedure. Radioembolization therefore combines radiation with embolization.

Investigations into yttrium-90 (90Y) and other radionuclides as part of a microsphere or particle for the treatment of cancer date back to the 1960s. Initial studies of resin 90Y in humans were reported in the late 1970s. The seminal work in a canine liver model demonstrating the safety and feasibility of using 90Y therapy for hepatic malignancies was reported in the late 1980s. Human studies of 90Y microsphere therapy in liver applications followed from the late 1980s through to the 1990s. These investigations established the safety of 90Y for intrahepatic applications as well as the tolerance of normal parenchyma to radioembolization. It should be noted that different disciplines use slightly different names for radioembolization: microsphere brachytherapy, microbrachytherapy, hepatic intra-arterial radiotherapy, and selective internal radiation therapy. The term radioembolization will be used in this chapter, as it is the preferred term per Society of Interventional Radiology standards document.

Mechanism of radioembolization

Radioembolization of liver tumor takes advantage of the unique vascular system of the liver. In normal liver tissue, approximately 70–80% of the organ's blood flow is supplied by the portal vein, and the hepatic artery accounts for the rest. This contrasts with both hepatocellular carcinoma (HCC) and metastatic tumors to the liver, which have approximately 80–100% of their blood flow supplied by the hepatic artery. This difference in perfusion is exploited by radioembolization, whereby radioactive microspheres doped with a radionuclide are used to produce intentional microembolization of the tumor capillary bed in the liver tumor(s) by delivering the microspheres through the hepatic artery and, subsequently, selectively targeting malignant disease.

Type
Chapter
Information
Interventional Oncology
Principles and Practice of Image-Guided Cancer Therapy
, pp. 44 - 51
Publisher: Cambridge University Press
Print publication year: 2016

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References

1. Flynn, WJ. [The treatment of pulmonary metastases with microspheres of yttrium 90.] Minerva Med 1967; 58 (99): 4498–4500. PubMed PMID: 5625456.Google Scholar
2. Greene, WM. Embolization of dog prostates with yttrium-90 microspheres. J Urol 1963; 90: 451–457. PubMed PMID: 14063380.Google Scholar
3. Wollner, I, Knutsen, C, Smith, P, Prieskorn, D, Chrisp, C, Andrews, J, et al. Effects of hepatic arterial yttrium 90 glass microspheres in dogs. Cancer 1988; 61 (7): 1336–1344. PubMed PMID: 3345490.Google Scholar
4. Wollner, IS, Knutsen, CA, Ullrich, KA, Chrisp, CE, Juni, JE, Andrews, JC, et al. Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs. Cancer Res 1987; 47 (12): 3285–3290. PubMed PMID: 3581069.Google Scholar
5. Gray, B, Hazel, G Van, Hope, M, Burton, M, Moroz, P, Anderson, J, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 2001; 12 (12): 1711–1720. PubMed PMID: 11843249.Google Scholar
6. Lewandowski, RJ, Thurston, KG, Goin, JE, Wong, CY, Gates, VL, Buskirk, M Van, et al. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135–150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. J Vasc Interv Radiol 2005; 16 (12): 1641–1651. PubMed PMID: 16371530.Google Scholar
7. Salem, R, Lewandowski, RJ, Atassi, B, Gordon, SC, Gates, VL, Barakat, O, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005; 16 (12): 1627–1639. PubMed PMID: 16371529.Google Scholar
8. Stubbs, RS, Cannan, RJ, Mitchell, AW. Selective internal radiation therapy (SIRT) with 90Yttrium microspheres for extensive colorectal liver metastases. Hepato-gastroenterology 2001; 48 (38): 333–337. PubMed PMID: 11379303.Google Scholar
9. Stubbs, RS, Cannan, RJ, Mitchell, AW. Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases. J Gastrointest Surg 2001; 5 (3): 294–302. PubMed PMID: 11360053.Google Scholar
10. Hazel, G Van, Blackwell, A, Anderson, J, Price, D, Moroz, P, Bower, G, et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol 2004; 88 (2): 78–85. PubMed PMID: 15499601.Google Scholar
11. Kulik, LM, Mulcahy, MF, Hunter, RD, Nemcek, AA, Jr., Abecassis, MM, Salem, R. Use of yttrium-90 microspheres (TheraSphere) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: a case report. Liver Transplant 2005; 11 (9): 1127–1131. PubMed PMID: 16123954.Google Scholar
12. Lau, WY, Ho, SK, Yu, SC, Lai, EC, Liew, CT, Leung, TW. Salvage surgery following downstaging of unresectable hepatocellular carcinoma. Ann Surg 2004; 240 (2): 299–305. PubMed PMID: 15273555. Pubmed Central PMCID: 1356407.Google Scholar
13. Salem, R, Lewandowski, RJ, Gates, VL, Nutting, CW, Murthy, R, Rose, SC, et al. Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol 2011; 22 (3): 265–278. PubMed PMID: 21353979.Google Scholar
14. Bierman, HR, Kelly, KH, Byron, RL, Jr., Dod, KS, Shimkin, MB. Studies on the blood supply of tumors in man. II. Intra-arterial nitrogen mustard therapy of cutaneous lesions. J Natl Cancer Inst 1951; 11 (5): 891–905. PubMed PMID: 14850957.Google Scholar
15. LNE –LNHB/CEA. Tables de radionucléides. www.nucleide.org/DDEP_WG/Nuclides/Y-90_tables.pdf (accessed March 14, 2014).
16. Dosimetry of beta rays and low-energy photons for brachytherapy with sealed sources. J ICRU 2004; 4 (2): 2. PubMed PMID: 24170821.
17. Simpkin, DJ, Mackie, TR. EGS4 Monte Carlo determination of the beta dose kernel in water. Med Physics 1990; 17 (2): 179–186. PubMed PMID: 2333044.Google Scholar
18. Selwyn, RG, Nickles, RJ, Thomadsen, BR, DeWerd, LA, Micka, JA. A new internal pair production branching ratio of 90Y: the development of a non-destructive assay for 90Y and 90Sr. Appl Radiat 2007; 65 (3): 318–327. PubMed PMID: 17045483.Google Scholar
19. Gates, VL, Esmail, AA, Marshall, K, Spies, S, Salem, R. Internal pair production of 90Y permits hepatic localization of microspheres using routine PET: proof of concept. J Nucl Med 2011; 52 (1): 72–76. PubMed PMID: 21149493.Google Scholar
20. Lhommel, R, Goffette, P, den Eynde, M Van, Jamar, F, Pauwels, S, Bilbao, JI, et al. Yttrium-90 TOF PET scan demonstrates high-resolution biodistribution after liver SIRT. Eur J Nucl Med Mol Imaging 2009; 36 (10): 1696. PubMed PMID: 19618182.Google Scholar
21. Gulec, SA, Mesoloras, G, Stabin, M. Dosimetric techniques in 90Y-microsphere therapy of liver cancer: The MIRD equations for dose calculations. J Nucl Med 2006; 47 (7): 1209–1211. PubMed PMID: 16818957.Google Scholar
22. Bolch, WE, Eckerman, KF, Sgouros, G, Thomas, SR. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry–standardization of nomenclature. J Nucl Med 2009; 50 (3): 477–484. PubMed PMID: 19258258.Google Scholar
23. Dezarn, WA, Cessna, JT, DeWerd, LA, Feng, W, Gates, VL, Halama, J, et al. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies. Med Physics 2011; 38 (8): 4824–4845. PubMed PMID: 21928655.Google Scholar
24. Ho, S, Lau, WY, Leung, TW, Chan, M, Ngar, YK, Johnson, PJ, et al. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours. Eur J Nucl Med 1996; 23 (8): 947–952. PubMed PMID: 8753684.Google Scholar
25. Ho, S, Lau, WY, Leung, TW, Chan, M, Johnson, PJ, Li, AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med 1997; 24 (3): 293–298. PubMed PMID: 9143467.Google Scholar
26. TheraSphere® [US package insert]. Rev. 11 ed. Ottawa, ON: Nordion (Canada) Inc.; 2011.
27. SIR-Spheres [US package insert]. SIR-TeX Medical Limited. Australia; 2011.
28. Erbe, EM, Day, DE. Chemical durability of Y2O3-Al2O3-SiO2 glasses for the in vivo delivery of beta radiation. J Biomed Mater Res 1993; 27 (10): 1301–1308. PubMed PMID: 8245044.Google Scholar
29. Nijsen, JF, Het Schip, AD Van, Steenbergen, MJ Van, Zielhuis, SW, Kroon-Batenburg, LM, de Weert, M Van, et al. Influence of neutron irradiation on holmium acetylacetonate loaded poly(L-lactic acid) microspheres. Biomaterials 2002; 23 (8): 1831–1839. PubMed PMID: 11950053.Google Scholar
30. Nijsen, JF, Zonnenberg, BA, Woittiez, JR, Rook, DW, Woudenberg, IA Swildens-van, Rijk, PP Van, 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. PubMed PMID: 10398817.Google Scholar
31. Zielhuis, SW, Nijsen, JF, Roos, R de, Krijger, GC, Rijk, PP Van, Hennink, WE, et al. Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application. Int J Pharm 2006; 311 (1–2): 69–74. PubMed PMID: 16439073.Google Scholar
32. Smits, ML, Nijsen, JF, den Bosch, MA Van, Lam, MG, Vente, MA, Huijbregts, JE, et al. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial. J Exp Clin Cancer Res 2010; 29: 70. PubMed PMID: 20550679. Pubmed Central PMCID: 2903532.Google Scholar
33. Smits, ML, Nijsen, JF, den Bosch, MA Van, 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): 1025–1034. PubMed PMID: 22920685.Google Scholar
34. 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. PubMed PMID: 17448867.Google Scholar
35. Giammarile, F, Bodei, L, Chiesa, C, Flux, G, Forrer, F, Kraeber-Bodere, F, et al. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging 2011; 38 (7): 1393–1406. PubMed PMID: 21494856.Google Scholar
36. Kennedy, A, Nag, S, Salem, R, et al. Recommendations for radio-embolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the Radio-embolization Brachytherapy Oncology Consortium (REBOC). Int J Radiat Oncol Biol Phys 2006; 68: 13–23.Google Scholar
37. Dezarn, A, Cessna, JT, DeWerd, LA, Feng, WZ, Gates, VL, Halama, J, et al. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for (90)Y microsphere brachytherapy in the treatment of hepatic malignancies. Med Phys 2011; 38: 4824–4845.Google Scholar
38. Liu, DM, Salem, R, Bui, JT, Courtney, A, Barakat, O, Sergie, Z, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol 2005; 16 (7): 911–935. PubMed PMID: 16002500.Google Scholar
39. Salem, R, Thurston, KG. Radioembolization with 90Yttrium 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): 1251–1278. PubMed PMID: 16923973. Epub 2006/08/23. eng.Google Scholar
40. Sangro, B, Bilbao, JI, Boan, J, Martinez-Cuesta, A, Benito, A, Rodriguez, J, et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2006; 66 (3): 792–800. PubMed PMID: 16904840.Google Scholar
41. National Council on Radiation Protection and Measurements. Management of Radionuclide Therapy Patients. NCRP report 155. Bethesda, MD: National Council on Radiation Protection and Measurements; 2006.
42. National Council on Radiation Protection and Measurements. Management of Persons Contaminated with Radionuclides. NCRP report 161. Bethesda, MD: National Council on Radiation Protection and Measurements; 2010.
43. International Commission on Radiological Protection. Release of patients after therapy with unsealed radionuclides. ICRP publication 94. Ann ICRP 2005; 34 (2).

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