Dosimetry in the Treatment of Liver Malignancies with Microspheres

Chapter

Abstract

The goal and the importance of dosimetry in the treatment of liver malignancies with radioactive microspheres are presented. A single acquisition is enough to provide the necessary information for the dosimetric calculations. This unique feature among all the other radiopharmaceuticals, together with the initial indications about the clinical impact of absorbed dose calculation, manifests in two interesting new phenomena in nuclear medicine therapy. From one side, dosimetry in radioembolization is adopted to plan the treatment in many more centers with respect to all the other radiopharmaceuticals. Second, this is the first and unique kind of therapy where all the microsphere producers are undertaking substantial efforts in order to implement dosimetry. This kind of dosimetry is extremely simple from the side of the technical methodology and on that of the calculation. The only problem is the potential discrepancy between the simulator particles (99mTc-MAA or trace administration of 166Ho microspheres) and the actual distribution of therapeutic particles.

Keywords

Radioembolization Treatment planning 90Y microspheres Dosimetry 

References

  1. 1.
    Chiesa C, Lassmann M. Dosimetry in nuclear medicine therapy. Q J Nucl Med Mol Imaging. 2011;55:2–4.PubMedGoogle Scholar
  2. 2.
    Wada N, Nakayama H, Suganuma N, Masudo Y, Rino Y, Masuda M, Imada T. Prognostic value of the sixth edition AJCC/UICC TNM classification for differentiated thyroid carcinoma with extrathyroid extension. J Clin Endocrinol Metab. 2007;92(1):215–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–35.CrossRefPubMedGoogle Scholar
  4. 4.
    Barone R, Borson-Chazot F, Valkema R, Walrand S, Chauvin F, Gogou L, Kvols LK, Krenning LP, Jamar F, Pauwels S. Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose–effect relationship. J Nucl Med. 2005;46:99S–106S.PubMedGoogle Scholar
  5. 5.
    Bergsma H, Konijnenberg M, van der Zwan WA, Kam BLR, Teunissen JJM, Kooij PP, Mauff KAL, Krenning EP, Kwekkeboom DJ. Nephrotoxicity after PRRT with 177Lu-DOTA-octreotate. Eur J Nucl Med Mol Imaging. 2016;43(10):1802–11.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):420–2.CrossRefGoogle Scholar
  7. 7.
    Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, et al. Yttrium90 radioembolization for intermediate-advanced hepatocarcinoma: a phase II study. Hepatology. 2013;57:1826–37.CrossRefPubMedGoogle Scholar
  8. 8.
    Kennedy AS, McNeillie P, Dezarn WA, Nutting C, Sangro B, Wertman D, Garafalo M, Liu D, Coldwell D, Savin M, Jakobs T, Rose S, Warner R, Carter D, Sapareto S, Nag S, Gulec S, Calkins A, Gates VL, Salem R. Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys. 2009;74:1494–500.CrossRefPubMedGoogle Scholar
  9. 9.
    Strigari L, Sciuto R, Rea S, Carpanese L, Pizzi G, Soriani A, Iaccarino G, Benassi M, Ettorre GM, Maini CL. Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y SIR spheres: radiobiological considerations. J Nucl Med. 2010;51:1377–85.CrossRefPubMedGoogle Scholar
  10. 10.
    Cremonesi M, Chiesa C, Strigari L, Ferrari M, Botta F, Guerriero F, De Cicco C, Bonomo G, Orsi F, Bodei L, Di Dia A, Grana CM, Orecchia R. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol. 2014;4:210.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Garin E, Rolland Y, Pracht M, Le Sourd S, Laffont S, Mesbah H, Haumont LA, Lenoir L, Rohou T, Brun V, Edeline J. High impact of macroaggregated albumin-based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microsphere radioembolization. Liver Int. 2017;37:101–10.CrossRefPubMedGoogle Scholar
  12. 12.
    SIR-Spheres. Yttrium-90 microspheres [package insert]. Sirtex Medical, Lane Cove. 2004. http://www.sirtex.com/files/US20Package20Insert1.pdf.
  13. 13.
    Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Mali WP, van Het Schip AD, Zonnenberg BA. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012;13:1025–34.CrossRefPubMedGoogle Scholar
  14. 14.
    Bianchi L, Baroli A, Marzoli L, Verusio C, Chiesa C, Pozzi L. Prospective dosimetry with 99mTc-MDP in metabolic radiotherapy of bone metastases with 153Sm-EDTMP. Eur J Nucl Med Mol Imaging. 2009;36:122–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Jiang M, Fishman A, Nowakowski FS, Heiba S, Zhang Z, Knesaurek K, Weintraub J, Machac J. Segmental perfusion differences on paired Tc-99m macroaggregated albumin (MAA) hepatic perfusion imaging and yttrium-90 (Y-90) bremsstrahlung imaging studies in SIR-sphere radioembolization: associations with angiography. J Nucl Med Radiat Ther. 2012;3:1.CrossRefGoogle Scholar
  16. 16.
    Wondergem M, Smits ML, Elschot M, de Jong HW, Verkooijen HM, van den Bosch MA, Nijsen JF, Lam MG. 99mTc-macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization. J Nucl Med. 2013;54:1294–301.CrossRefPubMedGoogle Scholar
  17. 17.
    Elschot M, Nijsen JFW, Lam MGEH, et al. 99mTc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with 166Ho-microspheres. Eur J Nucl Med Mol Imaging. 2014;41:1965–75.CrossRefPubMedGoogle Scholar
  18. 18.
    Zielhuis SW, Nijsen JFW, de Roosa R, Krijger GC, van Rijk PP, Hennink WE, van het Schip AD. Production of GMP-grade radioactive holmium loaded poly(l-lactic acid) microspheres for clinical application. Int J Pharm. 2006;311:69–74.CrossRefPubMedGoogle Scholar
  19. 19.
    Ahmadzadehfar H, Meyer PCC, Bundschuh R, Muckle M, Gärtner F, Essler SHH. Evaluation of the delivered activity of yttrium-90 resin microspheres using sterile water and 5% glucose during administration. EJNMMI Res. 2015;5:54.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gnesin S, Canetti L, Adib S, Cherbuin N, Silva Monteiro M, Bize P, Denys A, Prior JO, Baechler S, Boubaker A. Partition model-based 99mTc-MAA SPECT/CT predictive dosimetry compared with 90Y TOF PET/CT posttreatment dosimetry in radioembolization of hepatocellular carcinoma: a quantitative agreement comparison. J Nucl Med. 2016;57(11):1672–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Willowson KP, Tapner M, QUEST Investigator Team, Bailey DL. A multi-centre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization. Eur J Nucl Med Mol Imaging. 2015;42(8):1202–22.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Morosi C, Camerini T, Carrara M, Pellizzari S, Negri A, Aliberti G, Sposito C, Bhoori S, Facciorusso A, Civelli E, Lanocita R, Padovano B, Migliorisi M, Seregni E, Marchianò A, Crippa F, Mazzaferro V. Radioembolization of hepatocarcinoma with 90-Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology. Eur J Nucl Med Mol Imaging. 2015;42:1718–38.CrossRefPubMedGoogle Scholar
  23. 23.
    Lam MG, Goris ML, Iagaru AH, Mittra ES, Louie JD, Sze DY. Prognostic utility of 90Y radioembolization dosimetry based on fusion 99mTc-macroaggregated albumin-99mTc-sulfur colloid SPECT. J Nucl Med. 2013;54(12):2055–61.CrossRefPubMedGoogle Scholar
  24. 24.
    Kokabi N, Galt JR, Xing M, Camacho JC, Barron BJ, Schuster DM, Kim HS. A simple method for estimating dose delivered to hepatocellular carcinoma after yttrium-90 glass-based radioembolization therapy: preliminary results of a proof of concept study. J Vasc Interv Radiol. 2014;25:277–87.CrossRefPubMedGoogle Scholar
  25. 25.
    D’Arienzo M, Chiaramida P, Chiacchiararelli L, Coniglio A, Cianni R, Salvatori R, Ruzza A, Scopinaro F, Bagni O. 90Y PET-based dosimetry after selective internal radiotherapy treatments. Nucl Med Commun. 2012;33:633–40.CrossRefPubMedGoogle Scholar
  26. 26.
    Giammarile F, Bodei L, Chiesa C, Flux G, Forrer F, Kraeber-Bodere F, Brans B, Lambert B, Konijnenberg M, Borson-Chazot F, Tennvall J, Luster M. EANM procedure guidelines for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging. 2011;38(7):1393–406.CrossRefPubMedGoogle Scholar
  27. 27.
    Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Sposito C, Bhoori S, Morosi C, Pellizzari S, Negri A, Civelli E, Lanocita R, Camerini T, Bampo C, Carrara M, Seregni E, Marchianò A, Mazzaferro V, Bombardieri E. A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres. Q J Nucl Med Mol Imaging. 2012;56:503–8.PubMedGoogle Scholar
  28. 28.
    Lyman JT. Complication probability as assessed from dose-volume histograms. Radiat Res. 1995;104:13–9.CrossRefGoogle Scholar
  29. 29.
    Garin E, Rolland Y, Laffont S, Edeline J. Clinical impact of 99mTc-MAA SPECT/CT-based dosimetry in the radioembolization of liver malignancies with 90Y-loaded microspheres. Eur J Nucl Med Mol Imaging. 2016;43:559–75.CrossRefPubMedGoogle Scholar
  30. 30.
    Garin E, Lenoir L, Edeline J, Laffont S, Mesbah H, Porée P, Sulpice L, Boudjema K, Mesbah M, Guillygomarc'h A, Quehen E, Pracht M, Raoul JL, Clement B, Rolland Y, Boucher E. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept. Eur J Nucl Med Mol Imaging. 2013;40:1057–68.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Leung TW, Lau WY, Ho SK, Ward SC, Chow JH, Chan MS, Metreweli C, Johnson PJ, Li AK. Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys. 1995;33:919–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Salem R, Parikh P, Atassi B, Lewandowski RJ, Ryu RK, Sato KT, Gates VL, Ibrahim S, Mulcahy MF, Kulik L, Liu DM, Riaz A, Omary RA, Kennedy AS. Incidence of radiation pneumonitis after hepatic intra-arterial radiotherapy with yttrium-90 microspheres assuming uniform lung distribution. Am J Clin Oncol. 2008;31:431–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Walrand S, Hesse M, Jamar F, Lhommel R. A hepatic dose-toxicity model opening the way toward individualized radioembolization planning. J Nucl Med. 2014;55(8):1317–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Walrand S, Hesse M, Chiesa C, Lhommel R, Jamar F. The low hepatic toxicity per gray of 90Y glass microspheres is linked to their transport in the arterial tree favoring a nonuniform trapping as observed in posttherapy PET imaging. J Nucl Med. 2014;55:135–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Sangro B, Gil-Alzugaray B, Rodriguez J, Sola I, Martinez-Cuesta A, Viudez A, Chopitea A, Iñarrairaegui M, Arbizu J, Bilbao JI. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer. 2008;112:1538–46.CrossRefPubMedGoogle Scholar
  36. 36.
    Gavanier M, Ayav A, Sellal C, Orry X, Claudon M, Bronowicki JP, Laurent V. CT imaging findings in patients with advanced hepatocellular carcinoma treated with sorafenib: alternative response criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumor (mRECIST)) versus RECIST 1.1. Eur J Radiol. 2016;85(1):103–12.CrossRefPubMedGoogle Scholar
  37. 37.
    Pasciak AS, Bourgeois AC, Bradley YC. A microdosimetric analysis of tumor absorbed-dose as a function of the number of microspheres per unit volume in yttrium-90 radioembolization. J Nucl Med. 2016;57(7):1020–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Flamen P, Vanderlinden B, Delatte P, et al. Corrigendum: multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolization therapy with yttrium-90 labeled resin microspheres. Phys Med Biol. 2014;59:2549.CrossRefGoogle Scholar
  39. 39.
    van den Hoven AF, Rosenbaum CE, Elias SG, de Jong HW, Koopman M, Verkooijen HM, Alavi A, van den Bosch MA, Lam MG. Insights into the dose-response relationship of radioembolization with resin 90Y-microspheres: a prospective cohort study in patients with colorectal cancer liver metastases. J Nucl Med. 2016;57(7):1014–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Chiesa C. The individualized dosimetry in the radioembolization of hepatocarcinoma with 90Y microspheres. Phys Med. 2016;32:169–70. http://www.physicamedica.com/pb/assets/raw/Health%20Advance/journals/ejmp/1stECMP_abstracts_EJMP32S3.pdf CrossRefGoogle Scholar
  41. 41.
    Sjögreen Gleisner K, Spezi E, Solny P, Gabina PM, Cicone F, Stokke C, Chiesa C, Paphiti M, Brans B, Sandström M, Tipping J, Konijnenberg M, Flux G. Variations in the practice of molecular radiotherapy and implementation of dosimetry: results from a European survey. EJNMMI Phys. 2017;4:28. doi  10.1186/s40658-017-0193-4.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nuclear MedicineFoundation IRCCS Istituto Nazionale TumoriMilanItaly

Personalised recommendations