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EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds

  • Francesco GiammarileEmail author
  • Lisa Bodei
  • Carlo Chiesa
  • Glenn Flux
  • Flavio Forrer
  • Françoise Kraeber-Bodere
  • Boudewijn Brans
  • Bieke Lambert
  • Mark Konijnenberg
  • Françoise Borson-Chazot
  • Jan Tennvall
  • Markus Luster
  • the Therapy, Oncology and Dosimetry Committees
Guidelines

Abstract

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10–20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918–928, 1985); Schafer and Sorrell (Lancet 353:1253–1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for 131I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901–906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical 131I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with 90Y-microspheres. 90Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere®, MDS Nordion, Kanata, ON, Canada). Since 90Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.

Keywords

Guidelines Nuclear medicine Liver cancer 131I-Ethiodized oil 131I-Lipiodol Lipiocis® 90Y-Microspheres SIR-Spheres® TheraSphere® Resin-based spheres Glass spheres Radiomicrospheres 

References

  1. 1.
    Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985;56:918–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Schafer DF, Sorrell MF. Hepatocellular carcinoma. Lancet 1999;353:1253–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Leong As-Y, Liew CT, Lau JWY, Johnson PJ, editors. Hepatocellular carcinoma: contemporary diagnosis, investigation and management. London: Arnold; 1999.Google Scholar
  4. 4.
    Novell JR, Hilson A, Hobbs KE. Therapeutic aspects of radio-isotopes in hepatobiliary malignancy. Br J Surg 1991;78:901–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Raoul JL, Guyader D, Bretagne JF, Duvauferrier R, Bourguet P, Bekhechi D, 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.PubMedGoogle Scholar
  6. 6.
    Raoul JL, Guyader D, Bretagne JF, Heautot JF, Duvauferrier R, Bourguet P, et al. Prospective randomized trial of chemoembolization versus intra-arterial injection of 131I-labeled-iodized oil in the treatment of hepatocellular carcinoma. Hepatology 1997;26:1156–61.PubMedGoogle Scholar
  7. 7.
    Lau WY, Lai EC, Leung TW, Yu SC. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg 2008;247:43–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Leung WT, Lau WY, Ho SK, Chan M, Leung NW, Lin J, et al. Measuring lung shunting in hepatocellular carcinoma with intrahepatic-arterial technetium-99m macroaggregated albumin. J Nucl Med 1994;35:70–3.PubMedGoogle Scholar
  9. 9.
    Lambert B, Mertens J, Sturm EJ, Stienaers S, Defreyne L, D’Asseler Y. 99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with 90Y microspheres. Eur J Nucl Med Mol Imaging 2010;37:2328–33.PubMedCrossRefGoogle Scholar
  10. 10.
    Ehrhardt GJ, Day DE. Therapeutic use of Y-90 microspheres. Int J Radiat Appl Instrum Part B Nucl Med Biol 1987;14:233–42.Google Scholar
  11. 11.
    Lau WY, Ho S, Leung TW, Chan M, Ho R, Johnson PJ, et al. Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres. Int J Radiat Oncol Biol Phys 1998;40:583–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Dancey JE, Shepherd FA, Paul K, Sniderman KW, Houle S, Gabrys J, et al. Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med 2000;41:1673–81.PubMedGoogle Scholar
  13. 13.
    Stubbs RS, Cannan RJ, Mitchell AW. Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases. J Gastrointest Surg 2001;5:294–302.PubMedCrossRefGoogle Scholar
  14. 14.
    Geschwind JFH, Salem R, Carr BI, Soulen MC, Thurston KG, Goin KA, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 2004;127:S194–205.PubMedCrossRefGoogle Scholar
  15. 15.
    Kennedy AS, Nutting DO, Coldwell D, Gaiser J, Drachenberg C. Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys 2004;60:1552–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Goin JE, Salem R, Carr BI, Dancey JE, Soulen MC, Geschwind JFH, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: a risk-stratification analysis. J Vasc Interv Radiol 2005;16:195–203.PubMedGoogle Scholar
  17. 17.
    Sharma RA, Van Hazel G, Morgan B, Berry D, Blanshard K, Price D, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 2007;25:1099–106.PubMedCrossRefGoogle Scholar
  18. 18.
    Gray B, Van Hazel G, 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;12:1711–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Carr BI. Hepatic arterial 90yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 2004;10:S107–10.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Hazel G, 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;88:78–85.PubMedCrossRefGoogle Scholar
  21. 21.
    Sangro B, Bilbao J, 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;66:792–800.PubMedCrossRefGoogle Scholar
  22. 22.
    Garin E, Rolland Y, Boucher E, Ardisson V, Laffont S, Boudjema K, et al. First experience of hepatic radioembolization using microspheres labelled with yttrium-90 (TheraSphere): practical aspects concerning its implementation. Eur J Nucl Med Mol Imaging 2010;37:453–61.PubMedCrossRefGoogle Scholar
  23. 23.
    Sarfaraz M, Kennedy AS, Lodge MA, Li XA, Wu X, Yu CX. Radiation absorbed dose distribution in a patient treated with yttrium-90 microspheres for hepatocellular carcinoma. Med Phys 2004;31:2449–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Bacher K, Brans B, Monsieurs M, De Winter F, Dierckx RA, Thierens H. Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary? Eur J Nucl Med Mol Imaging 2002;29:1311–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002;53:810–21. Erratum in: Int J Radiat Oncol Biol Phys 2002;53:1422.PubMedCrossRefGoogle Scholar
  26. 26.
    Semenenko VA, Li XA. Lyman-Kutcher-Burman NTCP model parameters for radiation pneumonitis and xerostomia based on combined analysis of published clinical data. Phys Med Biol 2008;53:737–55.PubMedCrossRefGoogle Scholar
  27. 27.
    Salem R, Thurston KG, Carr BI, Goin JE, Geschwind JF. Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. J Vasc Interv Radiol 2002;13:S223–9.PubMedCrossRefGoogle Scholar
  28. 28.
    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;17:1251–78.PubMedCrossRefGoogle Scholar
  29. 29.
    Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics. J Vasc Interv Radiol 2006;17:1425–39.PubMedCrossRefGoogle Scholar
  30. 30.
    Salem R, Thurston KG. 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;17:1571–94.PubMedCrossRefGoogle Scholar
  31. 31.
    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;47:1209–11.PubMedGoogle Scholar
  32. 32.
    Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22.PubMedGoogle Scholar
  33. 33.
    Cremonesi M, Ferrari M, Bartolomei M, Orsi F, Bonomo G, Aricò D, et al. Radioembolisation with 90Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment. Eur J Nucl Med Mol Imaging 2008;35:2088–96.PubMedCrossRefGoogle Scholar
  34. 34.
    Yorke ED, Jackson A, Fox RA, Wessels BW, Gray BN. Can current models explain the lack of liver complications in Y-90 microsphere therapy? Clin Cancer Res 1999;5:3024s–30.PubMedGoogle Scholar
  35. 35.
    Chiesa C, Maccauro M, Romito R, Spreafico C, Pellizzari P, Negri A, et al. Need feasibility and convenience of dosimetric treatment planning in liver selective internal radiation therapy with 90Y microspheres: the experience on the National Cancer Institute of Milan. Q J Nucl Med Mol Imaging 2011;55:168–97.PubMedGoogle Scholar
  36. 36.
    Strigari L, Sciuto R, Rea S, Carpanese L, Pizzi G, Soriani A, et al. Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: radiobiologic considerations. J Nucl Med 2010;51:1377–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Lhommel R, Goffette P, Van den Eynde M, 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;36:1696.PubMedCrossRefGoogle Scholar
  38. 38.
    Bernal P, Raoul JL, Stare J, Sereegotov E, Sundram FX, Kumar A, et al. International Atomic Energy Agency-sponsored multination study of intra-arterial rhenium-188-labeled lipiodol in the treatment of inoperable hepatocellular carcinoma: results with special emphasis on prognostic value of dosimetric study. Semin Nucl Med 2008;38:S40–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Farmer DG, Rosove MH, Shaked A, Busuttil RW. Current treatment modalities for hepatocellular carcinoma. Ann Surg 1994;219:236–47.PubMedCrossRefGoogle Scholar
  40. 40.
    Krishnan S, Lin EH, Gunn GB, Chandra A, Beddar AS, Briere TM, et al. Conformal radiotherapy of the dominant liver metastasis: a viable strategy for treatment of unresectable chemotherapy refractory colorectal cancer liver metastases. Am J Clin Oncol 2006;29:562–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Kelley RK, Venook AP. Sorafenib in hepatocellular carcinoma: separating the hype from the hope. J Clin Oncol 2008;26:5845–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Monsieurs MA, Bacher K, Brans B, Vral A, De Ridder L, Dierckx RA, et al. Patient dosimetry for 131I-lipiodol therapy. Eur J Nucl Med Mol Imaging 2003;30:554–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Francesco Giammarile
    • 1
    Email author
  • Lisa Bodei
    • 2
  • Carlo Chiesa
    • 3
  • Glenn Flux
    • 4
  • Flavio Forrer
    • 5
  • Françoise Kraeber-Bodere
    • 6
  • Boudewijn Brans
    • 7
  • Bieke Lambert
    • 8
  • Mark Konijnenberg
    • 9
  • Françoise Borson-Chazot
    • 10
  • Jan Tennvall
    • 11
  • Markus Luster
    • 12
  • the Therapy, Oncology and Dosimetry Committees
  1. 1.Hospices Civils de Lyon, Service de Médecine NucléaireCentre Hospitalier Lyon-Sud and Université Claude Bernard Lyon 1, EA 3738LyonFrance
  2. 2.Division of Nuclear MedicineEuropean Institute of OncologyMilanItaly
  3. 3.Nuclear MedicineFoundation IRCCS National Tumour InstituteMilanItaly
  4. 4.Royal Marsden Hospital & Institute of Cancer ResearchSutton, SurreyUK
  5. 5.Department of Nuclear MedicineUniversity Hospital BaselBaselSwitzerland
  6. 6.University hospital, Rene Gauducheau cancer center, CRCNA unit 892NantesFrance
  7. 7.Department of Nuclear MedicineUniversity Medical Center MaastrichtMaastrichtThe Netherlands
  8. 8.Department of Nuclear MedicineGhent University HospitalGhentBelgium
  9. 9.Nuclear Medicine DepartmentErasmus MCRotterdamThe Netherlands
  10. 10.Hospices Civils de Lyon, Fédération d’endocrinologieUniversité Lyon 1, INSERM U664LyonFrance
  11. 11.Department of OncologyLund University, Skane University HospitalLundSweden
  12. 12.Department of Nuclear MedicineUniversity of UlmUlmGermany

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