Radioembolization (Yttrium-90 Microspheres) for Primary and Metastatic Hepatic Malignancies

Radioembolization using radioactive yttrium-90-labeled microspheres is gaining a stronger foothold in the management of primary and metastatic hepatic cancers. The expanding literature reveals good and encouraging results in both retrospective and prospective reports as demonstrated by low acute or late toxicity and high response rates. This treatment modality, which is most beneficial in patients with good liver reserve and low Eastern Cooperative Oncology Group performance status, has led to improved time to liver progression and extended overall patient survival. Although the phase III trials of radioembolization are ongoing as a first-line treatment of patients with metastatic colorectal cancer, there are sufficient phase II and retrospective clinical data supporting its use in salvage therapy for most patients. Patients with hepatocellular cancer, neuroendocrine tumors, and other primary sites, including breast and lung, have also shown promising response and survival increases in multi-institutional experiences.

[1]  K. Tatsch,et al.  Radiofrequency ablation after selective internal radiation therapy with Yttrium90 microspheres in metastatic liver disease-Is it feasible? , 2010, European journal of radiology.

[2]  J. Dancey,et al.  Comparison of post-embolization syndrome in the treatment of patients with unresectable hepatocellular carcinoma: Trans-catheter arterial chemo-embolization versus Yttrium-90 glass microspheres , 2004 .

[3]  T. Rich,et al.  Treatment of Primary Liver Tumors with Yttrium-90 Microspheres (TheraSphere®) in High Risk Patients: Analysis of Survival and Toxicities , 2009, Technology in cancer research & treatment.

[4]  O. Solheim [Treatment of patients with advanced cancer]. , 1973, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[5]  J. F. Perry,et al.  Treatment of patients with advanced cancer utilizing Y90 microspheres , 1965, Cancer.

[6]  G. van Hazel,et al.  Randomised phase 2 trial of SIR‐Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer , 2004, Journal of surgical oncology.

[7]  J. Prieto,et al.  Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. , 2006, International journal of radiation oncology, biology, physics.

[8]  D. Rubello,et al.  Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours. , 2007, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[9]  T. Pilgram,et al.  Salvage radioembolization of liver-dominant metastases with a resin-based microsphere: initial outcomes. , 2008, Journal of vascular and interventional radiology : JVIR.

[10]  W. Lau,et al.  What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres? , 2001, Hepato-gastroenterology.

[11]  K. McMasters,et al.  Safety of hepatic resection in metastatic disease to the liver after yttrium-90 therapy. , 2011, The Journal of surgical research.

[12]  K. McMasters,et al.  Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis? , 2009, Journal of the American College of Surgeons.

[13]  J. Dancey,et al.  Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: a risk-stratification analysis. , 2005, Journal of vascular and interventional radiology : JVIR.

[14]  Robert J. Lewandowski,et al.  Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere®): Assessment of Hepatic Arterial Embolization , 2006, CardioVascular and Interventional Radiology.

[15]  W. M. Greene EMBOLIZATION OF DOG PROSTATES WITH YTTRIUM-90 MICROSPHERES. , 1963, The Journal of urology.

[16]  T. Chua,et al.  Yttrium-90 Radiotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Preliminary Assessment of This Novel Treatment Option , 2010, Annals of Surgical Oncology.

[17]  Sanjay Gupta,et al.  Yttrium-90 microsphere radioembolotherapy of hepatic metastatic neuroendocrine carcinomas after hepatic arterial embolization. , 2008, Journal of vascular and interventional radiology : JVIR.

[18]  S. Houle,et al.  A phase I dose escalation trial of yttrium‐90 microspheres in the treatment of primary hepatocellular carcinoma , 1992, Cancer.

[19]  A. Li,et al.  Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. , 1994, British Journal of Cancer.

[20]  M. Mulcahy,et al.  Optimization of radioembolic effect with extended-shelf-life yttrium-90 microspheres: results from a pilot study. , 2009, Journal of vascular and interventional radiology : JVIR.

[21]  A. Benson,et al.  Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis , 2007, Hepatology.

[22]  M. Soulen,et al.  Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. , 2004, Gastroenterology.

[23]  R. Salem,et al.  Metabolic response after intraarterial 90Y-glass microsphere treatment for colorectal liver metastases: comparison of quantitative and visual analyses by 18F-FDG PET. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  F. Izzo,et al.  Clinical safety and efficacy of 90yttrium resin microspheres alone in unresectable, heavily pre-treated colorectal liver metastases: results of a phase II trial , 2008 .

[25]  E. Felix,et al.  Intraarterial yttrium 90 in the treatment of hepatic malignancy. , 1982, Radiology.

[26]  Y. Fong,et al.  Preoperative Y-90 microsphere selective internal radiation treatment for tumor downsizing and future liver remnant recruitment: a novel approach to improving the safety of major hepatic resections , 2009, World journal of surgical oncology.

[27]  D. Morris,et al.  Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases , 2008, Cancer.

[28]  C. Nutting,et al.  Use of yttrium-90 microspheres in the treatment of unresectable hepatic metastases from breast cancer. , 2007, International journal of radiation oncology, biology, physics.

[29]  M. Abecassis,et al.  Radiation Lobectomy: Preliminary Findings of Hepatic Volumetric Response to Lobar Yttrium-90 Radioembolization , 2009, Annals of Surgical Oncology.

[30]  Otto Muzik,et al.  Early dose response to yttrium-90 microsphere treatment of metastatic liver cancer by a patient-specific method using single photon emission computed tomography and positron emission tomography. , 2009, International journal of radiation oncology, biology, physics.

[31]  R. Cannan,et al.  Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases , 2001, Journal of Gastrointestinal Surgery.

[32]  S. Sailer,et al.  Dose selection of resin 90Y-microspheres for liver brachytherapy: A single center review , 2006 .

[33]  G. van Hazel,et al.  Regression of liver metastases following treatment with yttrium-90 microspheres. , 2010, The Australian and New Zealand journal of surgery.

[34]  M. Mulcahy,et al.  The effect of catheter-directed CT angiography on yttrium-90 radioembolization treatment of hepatocellular carcinoma. , 2005, Journal of vascular and interventional radiology : JVIR.

[35]  Kenneth G. Thurston,et al.  Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. , 2005, Journal of vascular and interventional radiology : JVIR.

[36]  R. Salem,et al.  Reduction of metastatic load to liver after intraarterial hepatic yttrium-90 radioembolization as evaluated by [18F]fluorodeoxyglucose positron emission tomographic imaging. , 2005, Journal of vascular and interventional radiology : JVIR.

[37]  M. Reiser,et al.  Radioembolization in patients with hepatic metastases from breast cancer. , 2008, Journal of vascular and interventional radiology : JVIR.

[38]  W. Ensminger,et al.  Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[39]  S. Houle,et al.  Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[40]  C. Nutting,et al.  Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. , 2006, International journal of radiation oncology, biology, physics.

[41]  M. Mulcahy,et al.  Radioembolization for the treatment of unresectable hepatocellular carcinoma: a clinical review. , 2008, World journal of gastroenterology.

[42]  P. Gibbs,et al.  Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies , 2005, Internal medicine journal.

[43]  M. Reiser,et al.  Hepatic yttrium-90 radioembolization of chemotherapy-refractory colorectal cancer liver metastases. , 2008, Journal of vascular and interventional radiology : JVIR.

[44]  Kenneth G. Thurston,et al.  Angiographic considerations in patients undergoing liver-directed therapy. , 2005, Journal of vascular and interventional radiology : JVIR.

[45]  D. Larsimont,et al.  Inducing resectability of chemotherapy refractory colorectal liver metastasis by radioembolization with yttrium-90 microspheres. , 2008, Clinical nuclear medicine.

[46]  G. M. Briggs,et al.  Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  M. Reiser,et al.  Mid-term results in otherwise treatment refractory primary or secondary liver confined tumours treated with selective internal radiation therapy (SIRT) using 90Yttrium resin-microspheres , 2007, European Radiology.

[48]  F. Miller,et al.  Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres. , 2007, AJR. American journal of roentgenology.

[49]  Daniel J Sargent,et al.  A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  K. Klose,et al.  Selective Internal Radiotherapy with Yttrium-90 Microspheres for Hepatic Metastatic Neuroendocrine Tumors: A Prospective Single Center Study , 2009, Digestion.

[51]  R. Stubbs,et al.  Selective internal radiation therapy (SIRT): a new modality for treating patients with colorectal liver metastases. , 2004, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[52]  D. Madoff,et al.  Hepatic yttrium-90 radioembolotherapy in metastatic colorectal cancer treated with cetuximab or bevacizumab. , 2007, Journal of vascular and interventional radiology : JVIR.

[53]  M. Abecassis,et al.  Use of yttrium‐90 microspheres (TheraSphere®) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: A case report , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[54]  V. Gebski,et al.  Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. , 2001, Annals of oncology : official journal of the European Society for Medical Oncology.

[55]  M. Mulcahy,et al.  Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. , 2007, Journal of vascular and interventional radiology : JVIR.

[56]  S. Sailer,et al.  Fractionation, dose selection, and response of hepatic metastases of neuroendocrine tumors after 90Y-microsphere brachytherapy , 2006 .

[57]  W. Gradishar,et al.  90Y radioembolization of metastatic breast cancer to the liver: toxicity, imaging response, survival. , 2007, Journal of vascular and interventional radiology : JVIR.

[58]  G. van Hazel,et al.  Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume , 2001, Journal of surgical oncology.

[59]  Kenneth G. Thurston,et al.  Use of Yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis. , 2004, Journal of vascular and interventional radiology : JVIR.

[60]  B. Carr Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: Interim safety and survival data on 65 patients , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[61]  C. Nutting,et al.  Radioembolization for Unresectable Neuroendocrine Hepatic Metastases Using Resin 90Y-Microspheres: Early Results in 148 Patients , 2008, American journal of clinical oncology.

[62]  I. Kamel,et al.  Salvage therapy for liver-dominant colorectal metastatic adenocarcinoma: comparison between transcatheter arterial chemoembolization versus yttrium-90 radioembolization. , 2009, Journal of vascular and interventional radiology : JVIR.

[63]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[64]  R. Stubbs,et al.  SELECTIVE INTERNAL RADIATION THERAPY WITH 90Y MICROSPHERES FOR COLORECTAL LIVER METASTASES: SINGLE‐CENTRE EXPERIENCE WITH 100 PATIENTS , 2006, ANZ journal of surgery.

[65]  A. Baum,et al.  Quality of life in patients diagnosed with primary hepatocellular carcinoma: Hepatic arterial infusion of Cisplatin versus 90‐Yttrium microspheres (Therasphere®) , 2004, Psycho-oncology.

[66]  R. Omary,et al.  The role of tumor vascularity in predicting survival after yttrium-90 radioembolization for liver metastases. , 2009, Journal of vascular and interventional radiology : JVIR.

[67]  A. Li,et al.  Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres. , 1998, International journal of radiation oncology, biology, physics.

[68]  A. Benson,et al.  Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival. , 2008, Radiology.

[69]  P. Gibbs,et al.  Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[70]  M. Abecassis,et al.  Yttrium‐90 microspheres (TheraSphere®) treatment of unresectable hepatocellular carcinoma: Downstaging to resection, RFA and bridge to transplantation , 2006, Journal of surgical oncology.

[71]  N. Habib,et al.  Assessment of response to treatment of unresectable liver tumours with 90Y microspheres: Value of FDG PET versus computed tomography , 2007, Nuclear medicine communications.

[72]  M. Abecassis,et al.  A Comparative Analysis of Transarterial Downstaging for Hepatocellular Carcinoma: Chemoembolization Versus Radioembolization , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[73]  D. C. Henckel,et al.  Case report. , 1995, Journal.

[74]  A. Benson,et al.  Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. , 2010, Gastroenterology.

[75]  A. Benson,et al.  Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. , 2007, International journal of radiation oncology, biology, physics.

[76]  C. Nutting,et al.  A First Report of Radioembolization for Hepatic Metastases From Ocular Melanoma , 2009, Cancer investigation.

[77]  A. Benson,et al.  90Y Radioembolization for Metastatic Neuroendocrine Liver Tumors: Preliminary Results From a Multi-institutional Experience , 2008, Annals of surgery.

[78]  S. Gulec,et al.  Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio , 2007, Journal of Translational Medicine.

[79]  C. Köhne,et al.  Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[80]  Kenneth G. Thurston,et al.  Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations. , 2006, Journal of vascular and interventional radiology : JVIR.

[81]  J. Thie,et al.  Regional yttrium-90 microsphere treatment of surgically unresectable and chemotherapy-refractory metastatic liver carcinoma. , 2006, Cancer biotherapy & radiopharmaceuticals.

[82]  I. Ariel RADIOACTIVE ISOTOPES FOR ADJUVANT CANCER THERAPY; ANIMAL EXPERIMENTATION AND PRELIMINARY RESULTS IN HUMAN APPLICATION. , 1964, Archives of surgery.

[83]  A. Benson,et al.  Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres , 2009, Cancer.

[84]  E. Cortesi,et al.  Selective Internal Radiation Therapy with SIR-Spheres for the Treatment of Unresectable Colorectal Hepatic Metastases , 2009, CardioVascular and Interventional Radiology.

[85]  P. Stetson,et al.  Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs. , 1987, Cancer research.

[86]  M. Thirlwell,et al.  Radioembolization for hepatic metastases. , 2002, Seminars in oncology.

[87]  A. Benson,et al.  Treatment of unresectable cholangiocarcinoma using yttrium‐90 microspheres , 2008, Cancer.

[88]  M. Nowitz,et al.  Evaluation of the role of CT in the assessment of response to selective internal radiation therapy in patients with colorectal liver metastases. , 2006, Australasian radiology.

[89]  P. Gibbs,et al.  A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy , 2005, BMC Cancer.

[90]  A. Benson,et al.  Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[91]  P. Bret,et al.  Hepatic malignancies: improved treatment with intraarterial Y-90. , 1988, Radiology.

[92]  J. Geschwind,et al.  Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations , 2007, CardioVascular and Interventional Radiology.

[93]  J. Dancey,et al.  Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. , 2005, Journal of vascular and interventional radiology : JVIR.

[94]  K. Ahrar,et al.  Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. , 2005, Journal of vascular and interventional radiology : JVIR.

[95]  R. Dowsett,et al.  90Yttrium microspheres for nonresectable liver cancer: the University of Connecticut Health Center experience. , 2007, Connecticut medicine.

[96]  J. Juni,et al.  Effects of hepatic arterial yttrium 90 glass microspheres in dogs , 1988, Cancer.