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Radionuclide Therapy of Tumors of the Liver and Biliary Tract

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Nuclear Oncology

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Abstract

The liver represents a frequent site for both primary cancer and metastatic disease. In these circumstances, liver-directed therapies such as cytoreduction via surgery or in situ ablative techniques may influence the natural history of the disease progression and improve clinical outcomes.

Radioembolization (RE) is a selective internal radiotherapy technique in which 131I-lipiodol or 90Y-/166Ho-microspheres are infused through the hepatic arteries. It is based on the fact that primary and secondary hepatic tumors are vascularized mostly by arterial blood flow, whereas the normal liver perfusion is mostly from the portal network. This enables high radiation doses to be delivered, sparing the surrounding non-malignant liver parenchyma.

Clinical evidence is currently available indicating that RE may play an important role in the management of hepatocellular carcinoma in intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors. Randomized clinical trials to better assess the potential beneficial and harmful outcomes of transarterial radioembolization either as a monotherapy or in combination with other systemic or locoregional therapies are ongoing.

In this chapter, we discuss some technical aspects, criteria for patient selection, current clinical evidence, and future directions of radioembolization for primary and secondary liver cancers.

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Abbreviations

[18F]FDG:

2-Deoxy-2-[18F]fluoro-d-glucose

5-FU:

5-Fluorouracil, a chemotherapy agent

68Ga-DOTANOC:

68Ga-DOTA-1-Nal3-octreotide

99mTc-MA:

99mTc-macroaggregated albumin

99mTcO4−:

99mTc-pertechnetate

AFP:

Alpha-fetoprotein, a circulating serum marker of hepatocellular carcinoma (and of testicular germ-cell cancer as well)

BECT:

Bremsstrahlung single-photon emission computed tomography

Bq:

Becquerel unit

BSAvc:

Body surface area

CA 19–9:

Carbohydrate antigen 19–9, a tumor-associated serum marker

CBCT:

Cone-beam computed tomography

ce-CT:

Contrast-enhanced x-ray computed tomography

CI:

Confidence interval

CR:

Complete response

CRC:

Colorectal cancer

CT:

X-ray computed tomography

DEB:

Drug-eluting bead

DOTA:

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid, a chelating agent for radiometals

EASL:

European Association for the Study of the Liver

ECOG:

Eastern Cooperative Oncology Group

eV:

Electron volt

GBq:

Giga-Becquerel (109 Becquerel)

Gy:

Gray unit (ionizing radiation dose in the International System of Units, corresponding to the absorption of one joule of radiation energy per kilogram of matter)

HCC:

Hepatocellular carcinoma

HDD:

4-Hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol, a chelating agent

ICC:

Intrahepatic cholangiocarcinoma

IRE:

Irreversible electroporation

keV:

Kiloelectron volt (103 eV)

LSF:

Lung shunt fraction

MBq:

Mega-Becquerel (106 Becquerel)

MDT:

Multidisciplinary tumor board

MeV:

Megaelectron volt (106 eV)

MIP:

Maximum intensity projection

MIRD:

Medical Internal Radiation Dose

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

NET:

Neuroendocrine tumor

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/computed tomography

PFS:

Progression-free survival

PR:

Partial response

PVT:

Portal vein thrombosis

RE:

Radioembolization

RECIST:

Response evaluation criteria in solid tumors

RFA:

Radiofrequency ablation

RILD:

Radiation-induced liver diseases

ROI:

Region of interest

SD:

Stable disease

SIRT:

Selective internal radiation therapy

SPECT/CT:

Single-photon emission computed tomography/computed tomography

SUV:

Standardized uptake value

SUVmax:

Standardized uptake value at point of maximum

TACE:

Transcatheter arterial chemoembolization

TAE:

Transarterial embolization

TARE:

Transarterialradioemobilization

VIPoma:

Neuroendocrine tumor producing vasoactive intestinal peptide

WHO:

World Health Organization

References

  1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–73.

    Article  PubMed  Google Scholar 

  2. Ryerson AB, Eheman CR, Altekruse SF, et al. Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122:1312–37.

    Article  PubMed  Google Scholar 

  3. Akinyemiju T, Abera S, Ahmed M, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level. JAMA Oncol. 2017;3:1683–91.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  5. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30.

    PubMed  Google Scholar 

  6. El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: Where are we? Where do we go? Hepatology. 2014;60:1767–75.

    Article  PubMed  Google Scholar 

  7. van der Pool AE, Damhuis RA, Ijzermans JN, et al. Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: a population-based series. Colorectal Dis. 2012;14:56–61.

    Article  PubMed  Google Scholar 

  8. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.

    Article  CAS  PubMed  Google Scholar 

  9. Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. Am J Roentgenol Radium Ther Nucl Med. 1965;93:200–8.

    CAS  PubMed  Google Scholar 

  10. Lawrence TS, Robertson JM, Anscher MS, et al. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys. 1995;31:1237–48.

    Article  CAS  PubMed  Google Scholar 

  11. Covey AM, Hussain SM. Liver-directed therapy for hepatocellular carcinoma: an overview of techniques, outcomes, and posttreatment imaging findings. AJR Am J Roentgenol. 2017;209:67–76.

    Article  PubMed  Google Scholar 

  12. Yu H, Burke CT. Comparison of percutaneous ablation technologies in the treatment of malignant liver tumors. Semin Interv Radiol. 2014;31:129–37.

    Article  CAS  Google Scholar 

  13. Stuart K. Chemoembolization in the management of liver tumors. Oncologist. 2003;8:425–37.

    Article  PubMed  Google Scholar 

  14. Geschwind JFH. Chemoembolization for hepatocellular carcinoma: where does the truth lie? J Vasc Interv Radiol. 2002;13:991–4.

    Article  PubMed  Google Scholar 

  15. Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007;46:474–81.

    Article  CAS  PubMed  Google Scholar 

  16. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.

    Article  PubMed  Google Scholar 

  17. Kettenbach J, Stadler A, Katzler IV, et al. Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent Radiol. 2008;31:468–76.

    Article  PubMed  Google Scholar 

  18. European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASLEORT clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.

    Article  Google Scholar 

  19. Vogl TJ, Mack MG, Balzer JO, et al. Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy. Radiology. 2003;229:457–64.

    Article  PubMed  Google Scholar 

  20. Nakajo M, Kobayashi H, Shimabukuro K, et al. Biodistribution and in vivo kinetics of iodine-131 lipiodol infused via the hepatic artery of patients with hepatic cancers. J Nucl Med. 1988;29:1066–77.

    CAS  PubMed  Google Scholar 

  21. Raoul JL, Bourguet P, Bretagne JF, et al. Hepatic artery injection of I-131-labelled lipiodol. I. Biodistribution study results in patients with hepatocellular carcinoma. Radiology. 1988;168:541–5.

    Article  CAS  PubMed  Google Scholar 

  22. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J VascInterv Radiol. 2005;16:1627–39.

    Article  Google Scholar 

  23. Smits ML, Nijsen JF, van den Bosch MA, 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(1):70.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nowicki ML, Cwikla JB, Sankowski AJ, et al. Initial study of radiological and clinical efficacy radioembolization using 188Re-human serum albumin (HSA) microspheres in patients with progressive, unresectable primary or secondary liver cancers. Med Sci Monit. 2014;20:1353–62.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bhattacharya S, Dhillon AP, Winslet MC, et al. Human liver cancer cells and endothelial cells incorporate iodised oil. Br J Cancer. 1996;73:877–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Madsen MT, Park CH, Thakur ML. Dosimetry of iodine-131 ethiodol in the treatment of hepatoma. J Nucl Med. 1988;29:1038–44.

    CAS  PubMed  Google Scholar 

  27. Monsieurs MA, Bacher K, Brans B, et al. Patient dosimetry for 131I-lipiodol therapy. Eur J Nucl Med Mol Imaging. 2003;30:554–61.

    Article  CAS  PubMed  Google Scholar 

  28. Leung WT, Lau WY, Ho S, et al. Selective internal radiation therapy with intra-arterial iodine-131-lipiodol in inoperable hepatocellular carcinoma. J Nucl Med. 1994;35:1313–8.

    CAS  PubMed  Google Scholar 

  29. Yoo HS, Park CH, Lee JT, et al. Small hepatocellular carcinoma: high dose internal radiation therapy with superselective intra-arterial injection of I-131-labeled Lipiodol. Cancer Chemother Pharmacol. 1994;33:S128–33.

    Article  PubMed  Google Scholar 

  30. Bhattacharya S, Novell JR, Dusheiko GM, Hilson AJ, Dick R, Hobbs KE. Epirubicin-lipiodol chemotherapy versus 131iodine-lipiodol radiotherapy in the treatment of unresectable hepatocellular carcinoma. Cancer. 1995;76:2202–10.

    Article  CAS  PubMed  Google Scholar 

  31. Raoul JL, Guyader D, Bretagne JF, 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.

    CAS  PubMed  Google Scholar 

  32. Boucher E, Garin E, Guillygomac’h A, et al. Intra-arterial injection of iodine-131-labeled lipiodol for treatment of hepatocellular carcinoma. Radiother Oncol. 2007;82:76–82.

    Article  CAS  PubMed  Google Scholar 

  33. Partensky C, Sassolas G, Henry L, et al. Intra-arterial iodine 131-labeled lipiodol as adjuvant therapy after curative liver resection for hepatocellular carcinoma: a phase 2 clinical study. Arch Surg. 2000;135:1298–300.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  PubMed  Google Scholar 

  35. Lee YS, Jeong JM, Kim YJ, et al. Synthesis of 188Re-labelled long chain alkyl diaminedithiol for therapy of liver cancer. Nucl Med Commun. 2002;23:237–42.

    Article  CAS  PubMed  Google Scholar 

  36. De Ruyck K, Lambert B, Bacher K, et al. Biologicdosimetry of 188Re-HDD/lipiodol versus 131I-lipiodol therapy in patients with hepatocellularcarcinoma. J Nucl Med. 2004;45:612–8.

    PubMed  Google Scholar 

  37. Kumar A, Srivastava DN, Chau TT, et al. Inoperable hepatocellularcarcinoma: transarterial188Re HDD-labelediodizedoil for treatment. Prospective multicenter clinicaltrial. Radiology. 2007;243:509–19.

    Article  PubMed  Google Scholar 

  38. Sato K, Lewandowski RJ, Bui JT, et al. Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol. 2006;29:522–9.

    Article  PubMed  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;17:1251–78.

    Article  PubMed  Google Scholar 

  40. Zielhuis SW, Nijsen JFW, De Roos R, et al. Production of GMP-grade radioactive holmium loaded poly(l-lactic acid) microspheres for clinical application. Int J Pharm. 2006;311:69–74.

    Article  CAS  PubMed  Google Scholar 

  41. Elschot M, Nijsen JF, Dam AJ, de Jong HW. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization. PLoS One. 2011;6:e26174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nijsen JFW, Seppenwoolde JH, Havenith T, Bos C, Bakker CJG, Van het Schip AD. Liver tumors: MR imaging of radioactive holmium microspheres – phantom and rabbit study. Radiology. 2004;231:491–9.

    Article  PubMed  Google Scholar 

  43. Seppenwoolde JH, Nijsen JFW, Bartels LW, Zielhuis SW, Van het Schip AD, Bakker CJ. Internal radiation therapy of liver tumors: qualitative and quantitative magnetic resonance imaging of the biodistribution of holmium-loaded microspheres in animal models. Magn Reson Med. 2004;53:76–84.

    Article  Google Scholar 

  44. Smits ML, Nijsen JF, van den Bosch MA, et al. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012;13:1025–34.

    Article  CAS  PubMed  Google Scholar 

  45. Braat AJAT, Prince JF, van Rooij R, et al. Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: a cohort study. Eur Radiol. 2018;28:920–8.

    Article  PubMed  Google Scholar 

  46. Prince JF, van den Bosch MAAJ, Nijsen JFW, et al. Efficacy of radioembolization with holmium-166 microspheres in salvage patients with liver metastases: a phase 2 study. J Nucl Med. 2018;59:582–8.

    Article  CAS  PubMed  Google Scholar 

  47. Hamami ME, Poeppel TD, Müller S, et al. SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer. J Nucl Med. 2009;50:688–92.

    Article  CAS  PubMed  Google Scholar 

  48. Levillain H, Bagni O, Deroose CM, et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging. 2021;48:1570–84.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Song YS, Paeng JC, Kim HC, et al. PET/CT-based dosimetry in 90Y-microsphere selective internal radiation therapy: single cohort comparison with pretreatment planning on 99mTc-MAA imaging and correlation with treatment efficacy. Medicine (Baltimore). 2015;94(23):e945.

    Article  Google Scholar 

  50. Gnesin S, Canetti L, Adib S, et al. Partition model-based99mTc-MAA SPECT/CT predictivedosimetrycompared with 90Y TOF PET/CT post-treatment dosimetry in radioembolization of hepatocellular carcinoma: a quantitative agreement comparison. J Nucl Med. 2016;57:1672–8.

    Article  CAS  PubMed  Google Scholar 

  51. Grosser OS, Ruf J, Kupitz D, et al. Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-microspheres used in pre-radioembolization dosimetry: influence on the liver-lung shunt. J Nucl Med. 2016;57:925–7.

    Article  CAS  PubMed  Google Scholar 

  52. Lenoir L, Edeline J, Rolland Y, et al. Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization. Eur J Nucl Med Mol Imaging. 2012;39:872–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ilhan H, Goritschan A, Paprottka P, et al. Predictive value of 99mTc-MAA SPECT for 90Y-labeled resin microsphere distribution in radioembolization of primary and secondary hepatic tumors. J Nucl Med. 2015;56:1654–60.

    Article  CAS  PubMed  Google Scholar 

  54. Sancho L, Rodriguez-Fraile M, Bilbao JI, et al. Is a technetium-99m macroaggregated albumin scan essential in the workup for selective internal radiation therapy with yttrium-90? An analysis of 532 patients. J Vasc Interv Radiol. 2017;28:1536–42.

    Article  PubMed  Google Scholar 

  55. 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. 2011;38:1393–406.

    Article  CAS  PubMed  Google Scholar 

  56. Smits MLJ, et al. The superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases. Eur J Nucl Med Mol Imaging. 2020;47:798–806.

    Article  CAS  PubMed  Google Scholar 

  57. D’Abadie P, Hesse M, Louppe A, et al. Microspheres used in liver radioembolization: from conception to clinical effects. Molecules. 2021;26(13):3966.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Strigari L, Sciuto R, Rea S, et al. Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR-spheres: radiobiologic considerations. J Nucl Med. 2010;51:1377–85.

    Article  CAS  PubMed  Google Scholar 

  59. Council Directive 2013/59/Euratom. Off J Eur Union. 2014;57.

    Google Scholar 

  60. van den Hoven AF, Rosenbaum CE, et al. 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;57:1014–9.

    Article  PubMed  Google Scholar 

  61. Chansanti O, Jahangiri Y, Matsui Y, et al. Tumor dose response in yttrium-90 resin microsphere embolization for neuroendocrine liver metastases: a tumor-specific analysis with dose estimation using SPECT-CT. J Vasc Interv Radiol. 2017;28:1528–35.

    Article  PubMed  Google Scholar 

  62. Willowson KP, Hayes AR, Chan DLH, et al. Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis. EJNMMI Res. 2017;7(1):46.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Levillain H, Duran Derijckere I, Marin G, et al. 90Y-PET/CT-based dosimetry after selective internal radiation therapy predicts outcome in patients with liver metastases from colorectal cancer. EJNMMI Res. 2018;8:60.

    Google Scholar 

  64. Levillain H, Duran Derijckere I, et al. Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study. Eur J Nucl Med Mol Imaging. 2019;46:2270–9.

    Article  PubMed  Google Scholar 

  65. Hermann A-L, Dieudonne A, Ronot M, et al. Relationship of tumor radiation-absorbed dose to survival and response in hepatocellular carcinoma treated with transarterial radioembolization with yttrium-90 in the SARAH study. Radiology. 2020;296:673–84.

    Article  PubMed  Google Scholar 

  66. Russell AH, Clyde C, Wasserman TH, et al. Accelerated hyperfractionated hepatic irradiation in the management of patients with liver metastases: results of the RTOG dose escalating protocol. Int J Radiat Oncol Biol Phys. 1993;27:117–23.

    Article  CAS  PubMed  Google Scholar 

  67. Ho S, Lau WY, Leung TW, et al. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumors. Eur J Nucl Med. 1996;23:947–52.

    Article  CAS  PubMed  Google Scholar 

  68. Pan CC, Kavanagh BD, Dawson LA, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76:S94–100.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dittmann H, Kopp D, Kupferschlaeger J, et al. A prospective study of quantitative SPECT/CT for evaluation of lung shunt fraction before SIRT of liver tumors. J Nucl Med. 2018;59:1366–72.

    Article  CAS  PubMed  Google Scholar 

  70. Kennedy AS, Dezarn WA, McNeillie P, et al. Fractionation, dose selection, and response of hepatic metastases of neuroendocrine tumors after 90Y-microsphere brachytherapy. Brachytherapy. 2006;5:103–4.

    Google Scholar 

  71. Kennedy AS, Dezarn WA, McNeillie P, et al. Dose selection of resin 90Y-micrspheres for liver brachytherapy: a single center review. Brachytherapy. 2006;5:104.

    Article  Google Scholar 

  72. Flamen P, Vanderlinden B, Delatte P, et al. Multimodality imaging can predict the metabolic response of unresectable colorectal liver metastases to radioembolisation therapy with yttrium-90 labeled resin microspheres. Phys Med Biol. 2008;53:6591–603.

    Article  PubMed  Google Scholar 

  73. Jiang M, Fischman A, Nowakowski FS, et al. 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;3:122.

    Article  CAS  Google Scholar 

  74. Wondergem M, Smits MLJ, Elschot M, et al. 99mTc-Macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization. J Nucl Med. 2013;54:1294–301.

    Google Scholar 

  75. Lau WY, Sangro B, Chen PJ, et al. Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90. Oncology. 2013;84:311–8.

    Article  CAS  PubMed  Google Scholar 

  76. Garin E, Lenoir L, Rolland Y, et al. Dosimetrybased on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53:255–63.

    Article  CAS  PubMed  Google Scholar 

  77. Mazzaferro V, Sposito C, Bhoori S, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826–37.

    Article  CAS  PubMed  Google Scholar 

  78. Ahmadzadehfar H, Muckle M, Sabet A, et al. The significance of bremsstrahlung SPECT/CT after yttrium-90 radioembolisation treatment in the prediction of extrahepatic side effects. Eur J Nucl Med Mol Imaging. 2011;39:309–15.

    Article  Google Scholar 

  79. Garin E, Tzelikas L, Guiu B, et al. Major impact of personalized dosimetry using 90Y loaded glass microspheres SIRT in HCC: final overall survival analysis of a multicenter randomized phase II study (DOSISPHERE-01). J Clin Oncol. 2020;38(Suppl 4):515–6.

    Google Scholar 

  80. Reinders MT, Smits Maarten LJ, et al. Holmium-166 microsphere radioembolization of hepatic malignancies. Semin Nucl Med. 2019;49(3):237–43.

    Article  PubMed  Google Scholar 

  81. Chiesa C, Maccauro M, Romito R, et al. Need, feasibility and convenience of dosimetric treatment planning in liver selective internal radiation therapy with 90Y microspheres: the experience of the National Tumor Institute of Milan. Q J Nucl Med Mol Imaging. 2011;55:168–97.

    CAS  PubMed  Google Scholar 

  82. Dewaraja YK, Devasia T, Kaza RK, et al. Prediction of tumor control in 90Y radioembolization by logit models with PET/CT-based metrics. J Nucl Med. 2020;61:104–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lau W, Kennedy A, Kim Y, et al. Patieny selection and activity planning guide for selective internal radio-therapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys. 2012;82:401–7.

    Article  PubMed  Google Scholar 

  84. Garin E, Rolland Y, Edeline J. 90Y-loaded microsphere SIRT of HCC patients with portal vein thrombosis: high clinical impact of 99mTc-MAA SPECT/CT-based dosimetry. Semin Nucl Med. 2019;49:218–26.

    Google Scholar 

  85. Rodriguez-Lago I, Carretero C, Herraiz M, et al. Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors. World J Gastroenterol. 2013;19:2035–40.

    Article  Google Scholar 

  86. Lhommel R, van Elmbt L, Goffette P, et al. Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-spheres. Eur J Nucl Med Mol Imaging. 2010;37:1654–62.

    Article  PubMed  Google Scholar 

  87. Kao YH, Tan EH, Lim KY, et al. Yttrium-90 internal pair production imaging using first generation PET/CT provides high resolution images for qualitative diagnostic purposes. Br J Radiol. 2012;85:1018–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wright CL, Zhang J, Tweedle MF, et al. Theranostic imaging of yttrium-90. Biomed Res Int. 2015;2015:481279.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Gnesin S, Canetti L, Adib S, et al. Partition model based99mTc-MAA SPECT/CT predictive dosimetry compared to90Y TOF PET/CT post treatment dosimetry in radioembolisation of hepatocellular carcinoma: a quantitative agreement comparison. J Nucl Med. 2016;57:1672–8.

    Article  CAS  PubMed  Google Scholar 

  90. Smits ML, et al. In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies. J Nucl Med. 2013;54:2093–100.

    Article  CAS  PubMed  Google Scholar 

  91. Seevinck PR, Seppenwoolde JH, de Wit TC, et al. Factors affecting the sensitivity and detection limits of MRI, CT, and SPECT for multimodal diagnostic and therapeutic agents. Anticancer Agents Med Chem. 2007;7:317–34.

    Article  CAS  PubMed  Google Scholar 

  92. van de Maat GH, et al. MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation. Eur Radiol. 2013;23:827–35.

    Article  PubMed  Google Scholar 

  93. Wong CY, Qing F, Savin M, et al. Reduction of metastatic load to liver after intra arterial hepatic yttrium-90 radioembolization as evaluated by [18F]fluorodeoxyglucose positron emission tomographic imaging. J Vasc Interv Radiol. 2005;16:1101–6.

    Article  PubMed  Google Scholar 

  94. Miller FH, Keppke AL, Reddy D, et al. Response of liver metastases after treatment with yttrium-90 microspheres: role of size, necrosis, and PET. AJR Am J Roentgenol. 2007;188:776–83.

    Article  PubMed  Google Scholar 

  95. Haug AR, Heinemann V, Bruns CJ, et al. 18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres. Eur J Nucl Med Mol Imaging. 2011;38:1037–45.

    Google Scholar 

  96. Sabet A, Ahmadzadehfar H, Bruhman J, et al. Survival in patients with hepatocellular carcinoma treated with 90Y-microsphere radioembolization. Prediction by 18F-FDG PET. Nuklearmedizin. 2014;53:39–45.

    Article  CAS  PubMed  Google Scholar 

  97. Hartenbach M, Weber S, Albert NL, et al. Evaluating treatment response of radioembolization in intermediate-stage hepatocellular carcinoma patients using 18F-fluoroethylcholine PET/CT. J Nucl Med. 2015;56:1661–6.

    Article  CAS  PubMed  Google Scholar 

  98. Zerizer I, Al-Nahhas A, Towey D, et al. The role of early 18F-FDG PET/CT in prediction of progression-free survival after 90Y radioembolization: comparison with RECIST and tumour density criteria. Eur J Nucl Med Mol Imaging. 2012;39:1391–9.

    Article  CAS  PubMed  Google Scholar 

  99. Sabet A, Meyer C, Aouf A, et al. Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer. Eur J Nucl Med Mol Imaging. 2015;42:370–6.

    Article  CAS  PubMed  Google Scholar 

  100. Haug AR, Tiega Donfack BP, Trumm C, et al. 18F-FDG PET/CT predicts survival after radioembolization of hepatic metastases from breast cancer. J Nucl Med. 2012;53:371–7.

    Google Scholar 

  101. Fidelman N, Kerlan Jr RK. Transarterial chemoembolization and 90Y radioembolization for hepatocellular carcinoma: review of current applications beyond intermediate-stage disease. AJR Am J Roentgenol. 2015;205:742–52.

    Article  PubMed  Google Scholar 

  102. Filippi L, Scopinaro F, Pelle G, et al. Molecular response assessed by 68Ga-DOTANOC and survival after 90Y microsphere therapy in patients with liver metastases from neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2016;43:432–40.

    Article  CAS  PubMed  Google Scholar 

  103. Johnson GE, Monsky WL, Valji K, et al. Yttrium-90 radioembolization as a salvage treatment following chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2016;27:1123–9.

    Article  PubMed  Google Scholar 

  104. Teo JY, Allen Jr JC, Ng DC, et al. A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90. HPB (Oxford). 2016;18:7–12.

    Article  Google Scholar 

  105. Kulik L, Vouche M, Koppe S, et al. Prospective randomized pilot study of Y90 +/− sorafenib as bridge to transplantation in hepatocellular carcinoma. J Hepatol. 2014;61:309–17.

    Article  CAS  PubMed  Google Scholar 

  106. Chow PK, Poon DY, Khin MW, et al. Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma. PLoS One. 2014;9(3):e90909.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Lorenzin D, Pravisani R, Leo CA, et al. Complete remission of unresectable hepatocellular carcinoma after combined sorafenib and adjuvant yttrium-90 radioembolization. Cancer Biother Radiopharm. 2016;31:65–9.

    Article  CAS  PubMed  Google Scholar 

  108. Dutton SJ, Kenealy N, Love SB, et al. FOXFIRE protocol: an open-label, randomised, phase III trial of 5-fluorouracil, oxaliplatin and folinic acid (OxMdG) with or without interventional selective internal radiation therapy (SIRT) as first-line treatment for patients with unresectable liver-only or liver-dominant metastatic colorectal cancer. BMC Cancer. 2014;14:497.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Sangha BS, Nimeiri H, Hickey R, Salem R, Lewandowski RJ. Radioembolization as a treatment strategy for metastatic colorectal cancer to the liver: what can we learn from the SIRFLOX trial? Curr Treat Options Oncol. 2016;17:26.

    Article  PubMed  Google Scholar 

  110. Salem R, Lewandowsky RJ, Mulcahy MF, et al. Radioembolisation for hepatocellular carcinoma using Yttrium-90 microspheres. a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52–64.

    Article  CAS  PubMed  Google Scholar 

  111. Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere®) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol. 2006;94:572–86.

    Article  CAS  PubMed  Google Scholar 

  112. Tohme S, Sukato D, Chen HW, et al. Yttrium-90 radioembolization as a bridge to liver transplantation: a single-institution experience. J Vasc Interv Radiol. 2013;24:1632–8.

    Article  PubMed  Google Scholar 

  113. Abdelfattah MR, Al-Sebayel M, Broering D, Alsuhaibani H. Radioembolization using yttrium-90 microspheres as bridging and downstaging treatment for unresectable hepatocellular carcinoma before liver transplantation: initial single-center experience. Transplant Proc. 2015;47:408–11.

    Article  CAS  PubMed  Google Scholar 

  114. Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2007;41:71–81.

    Article  Google Scholar 

  115. Ibrahim SM, Mulcahy MF, Lewandowski RJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 2008;113:2119–28.

    Article  CAS  PubMed  Google Scholar 

  116. Al-Adra DP, Gill RS, Axford SJ, et al. Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis. Eur J Surg Oncol. 2015;41:120–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rayar M, Sulpice L, Edeline J, et al. Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment. Ann Surg Oncol. 2015;22:3102–8.

    Article  CAS  PubMed  Google Scholar 

  118. Boehm LM, Jayakrishnan TT, Miura JT, et al. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015;111:213–20.

    Article  PubMed  Google Scholar 

  119. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.

    Article  CAS  PubMed  Google Scholar 

  120. Gray B, Van Hazel G, Hope M, 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.

    Article  CAS  PubMed  Google Scholar 

  121. Goin JE, Dancey JE, Hermann GA, et al. Treatment of unresectable metastatic colorectal carcinoma to the liver with intrahepatic Y-90 microspheres: a dose-ranging study. World J Nucl Med. 2003;2:216–25.

    Google Scholar 

  122. Van Hazel G, Blackwell A, Anderson J, et al. Randomisedphase 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.

    Article  PubMed  Google Scholar 

  123. Sharma RA, Van Hazel GA, Morgan B, 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.

    Article  CAS  PubMed  Google Scholar 

  124. van Hazel GA, Pavlakis N, Goldstein D, et al. Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. J Clin Oncol. 2009;27:4089–95.

    Article  CAS  PubMed  Google Scholar 

  125. Gibbs P, Heinemann V, Sharma NK, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol. 2015;33(Suppl):3502.

    Article  Google Scholar 

  126. Hong K, McBride JD, Georgiades CS, et al. Salvage therapy for liver-dominant colorectal metastatic adenocarcinoma: comparison between transcatheter arterial chemoembolization versus yttrium-90 radioembolization. J Vasc Interv Radiol. 2009;20:360–7.

    Article  PubMed  Google Scholar 

  127. Saxena A, Bester L, Shan L, et al. A systematic review on the safety and efficacy of yttrium-90 radioembolization for unresectable, chemorefractory colorectal cancer liver metastases. J Cancer Res Clin Oncol. 2014;140:537–47.

    Article  CAS  PubMed  Google Scholar 

  128. Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in patients. Am J Clin Oncol. 2008;31:271–9.

    Article  PubMed  Google Scholar 

  129. Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg. 2008;247:1029–35.

    Google Scholar 

  130. Mahnken AH. Current status of transarterial radioembolization. World J Radiol. 2016;8:449–59.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Regional Center of Nuclear Medicine, University Hospital of Pisa, Pisa, Italy

    Giuseppe Boni

  2. Nuclear Medicine Unit, Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Duccio Volterrani & Giuliano Mariani

  3. Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Federica Guidoccio

Authors
  1. Giuseppe Boni
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  2. Federica Guidoccio
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  3. Duccio Volterrani
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  4. Giuliano Mariani
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Correspondence to Giuseppe Boni .

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Editors and Affiliations

  1. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Duccio Volterrani

  2. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Paola A. Erba

  3. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    H. William Strauss

  4. Nuclear Medicine Unit Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Giuliano Mariani

  5. Molecular Imaging and Targeted Therapy Service Department of Radiology, Sloan Kettering Institute, New York, NY, USA

    Steven M. Larson

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Boni, G., Guidoccio, F., Volterrani, D., Mariani, G. (2022). Radionuclide Therapy of Tumors of the Liver and Biliary Tract. In: Volterrani, D., Erba, P.A., Strauss, H.W., Mariani, G., Larson, S.M. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-031-05494-5_51

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