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

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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.

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Notes

  1. Additionally, it is important to notice a very small abundance of emitted positrons, since 90Y-microsphere imaging is possible on positron emission tomography (PET) devices.

  2. 99mTc-labelled albumin microspheres are not widely available but could also be used.

  3. Planar and, possibly, single photon emission computed tomography (SPECT).

  4. Even in cases of palliative treatments, this criterion was defined essentially for radioprotection reasons.

  5. In this case, multiple steps proceeding with partial hepatic administration are possible.

  6. Preferably SPECT scintigraphy, as well as SPECT/CT hybrid imaging (or offline coregistration of available CT with SPECT).

  7. According to Semenenko and Li [26], the threshold for induction of radiation pneumonitis with external beam therapy is 17.5 Gy when the whole lung is uniformly irradiated with 2 Gy per daily fraction. These limits however cannot be applied as such to radionuclide treatments since (a) they refer to different dose rate and fractionation and above all (b) microsphere irradiation is microscopically nonuniform. No rigorous normal tissue complication probability curve is available for lung irradiated with microspheres. The empirical absorbed dose limit of 30 Gy (evaluated without attenuation correction) is generally adopted.

  8. Perchlorate administration prior to MAA scan could be necessary to exclude gastric uptake of free 99mTc.

  9. The shortest interval between labelling of MAA and scintigraphy should interleave, since the well-known MAA spontaneous unlabelling can simulate false gastrointestinal shunt, due to circulating 99mTc.

  10. \( BSA\left( {{m^2}} \right) = 0.20247\, \times \,height{(m)^{{0.725}}}\, \times \,weight{\left( {kg} \right)^{{0.425}}} \).

  11. Urinary excretion over the first 8 days is about 40% for Lipiocis®, whereas for SIR-Spheres® it is less than 0.1% and for TheraSpheres® less than 0.01%.

  12. The glass microspheres are placed directly in the reactor to activate the 90Y: the manufacturing process may result in increasing the amount of contaminants.

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Authors and Affiliations

  1. Hospices Civils de Lyon, Service de Médecine Nucléaire, Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon 1, EA 3738, Lyon, France

    Francesco Giammarile

  2. Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy

    Lisa Bodei

  3. Nuclear Medicine, Foundation IRCCS National Tumour Institute, Milan, Italy

    Carlo Chiesa

  4. Royal Marsden Hospital & Institute of Cancer Research, Sutton, Surrey, UK

    Glenn Flux

  5. Department of Nuclear Medicine, University Hospital Basel, Basel, Switzerland

    Flavio Forrer

  6. University hospital, Rene Gauducheau cancer center, CRCNA unit 892, Nantes, France

    Françoise Kraeber-Bodere

  7. Department of Nuclear Medicine, University Medical Center Maastricht, Maastricht, The Netherlands

    Boudewijn Brans

  8. Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium

    Bieke Lambert

  9. Nuclear Medicine Department, Erasmus MC, Rotterdam, The Netherlands

    Mark Konijnenberg

  10. Hospices Civils de Lyon, Fédération d’endocrinologie, Université Lyon 1, INSERM U664, Lyon, France

    Françoise Borson-Chazot

  11. Department of Oncology, Lund University, Skane University Hospital, Lund, Sweden

    Jan Tennvall

  12. Department of Nuclear Medicine, University of Ulm, Ulm, Germany

    Markus Luster

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  1. Francesco Giammarile
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Giammarile, F., Bodei, L., Chiesa, C. 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 38, 1393–1406 (2011). https://doi.org/10.1007/s00259-011-1812-2

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