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Hepatic Radioembolization
Jessica Wen, MD; Christos Georgiades, MD, PhD
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KEY FACTS

  • Terminology

    • Procedure

      • Post Procedure

        • Outcomes

          TERMINOLOGY

          • Definitions

            • Selective internal radiotherapy (SIRT) or radioembolization or transarterial radioembolization (TARE)
              • Anatomic & physiologic principles
                • Most of normal liver parenchyma is supplied via portal vein (70-80%)
                • Nearly all liver tumor supply is via the hepatic artery (90-100%)
                • Therefore, intraarterial treatment will preferentially target tumor & spare normal live parenchyma
              • Yttrium-90 (⁹⁰Y) is pure β emitter (energetic electrons)
                • Half-value layer is 2.5 mm; this means 50% of β particles are absorbed at every 2.5 mm of tissue penetration
                • At 10 mm (4 half-value layers), nearly all (93.75%) β particles have been absorbed
                • Small portion of β particle absorption (0.01%) is due to bremsstrahlung (breaking, decelerating), which results in γ radiation
                • γ radiation has much longer half-value layer; therefore, treated patients do emit some γ radiation
                • Half-life of ⁹⁰Y is 64 hours
              • Technical objective
                • Deliver ⁹⁰Y-loaded particles throughout arterial bed of tumor
                • Requires delivery of at least 120 Gy to tumor; less than 100 Gy appears to be ineffective
              • There are 2 commercially available ⁹⁰Y particles
                • Resin microspheres with median diameter 30 μm (SIR-Spheres, Sirtex Medical; North Sydney, Australia)
                  • Lower radiation dose per particle (lower specific activity); therefore, significant embolization effect
                • Glass microsphere median diameter 25 μm (TheraSphere, MDS Nordion; Ottowa, Canada)
                  • Higher radiation dose per particle (higher specific activity); therefore, little embolic effect
            • Pretreatment evaluation/shunt study
              • Angiogram of hepatic arterial supply
                • (1) Define arterial supply to tumor & plan ⁹⁰Y delivery (split dose may be needed)
                • (2) Embolize (if needed) arterial branches that may be at risk for inadvertent nontarget embolization
                  • Commonly gastroduodenal artery, falciform artery, left or right gastric artery
                • (3) Calculate shunt ratio
              • Shunt study
                • Injection of ⁹⁹mTc-MAA (macroaggregated albumin) via catheter in anticipated position of ⁹⁰Y treatment
                • Followed by radionuclide lung-liver perfusion scan
                  • Calculate percent activity in lung over total activity (lung & liver)
                  • Shunt of < 15% is considered safe in patients with normal lung function
                  • If COPD or other lung disease, consider lowering acceptable shunt fraction (< 10%)
            • ⁹⁰Y microsphere administration
              • Usually performed within 2 weeks of pretreatment study
              • If > 6 months from shunt study, consider repeating shunt study as tumor hemodynamics may have changed

          PREPROCEDURE

          • Indications

            • Contraindications

              • Preprocedure Imaging

                • Getting Started

                  • Radioactive Microspheres

                    PROCEDURE

                    • Patient Position/Location

                      • Equipment Preparation

                        • Procedure Steps

                          • Alternative Procedures/Therapies

                            POST PROCEDURE

                            • Things to Do

                              • Postprocedure Imaging/Follow-Up

                                OUTCOMES

                                • Complications

                                  • Expected Outcomes

                                    Selected References

                                    1. Biederman DM et al: Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein Invasion: resin versus glass microspheres. J Vasc Interv Radiol. 27(6):812-821.e2, 2016
                                    2. van Hazel GA et al: SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 34(15):1723-31, 2016
                                    3. Njei B et al: Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 61(1):191-9, 2015
                                    4. Dutton SJ 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. 14:497, 2014
                                    5. Gibbs P et al: Selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 14:897, 2014
                                    6. Wang DS et al: Prophylactic topically applied ice to prevent cutaneous complications of nontarget chemoembolization and radioembolization. J Vasc Interv Radiol. 24(4):596-600, 2013
                                    7. Lau WY et al: Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys. 82(1):401-7, 2012
                                    8. Yaghmai V et al: Response to treatment series: part 2, tumor response assessment--using new and conventional criteria. AJR Am J Roentgenol. 197(1):18-27, 2011
                                    9. Lencioni R et al: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30(1):52-60, 2010
                                    10. Salem R et al: Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 138(1):52-64, 2010
                                    11. Ibrahim SM et al: Radiologic findings following Y90 radioembolization for primary liver malignancies. Abdom Imaging. 34(5):566-81, 2009
                                    12. Riaz A et al: Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J Vasc Interv Radiol. 20(9):1121-30; quiz 1131, 2009
                                    13. Shariff MI et al: Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 3(4):353-67, 2009
                                    14. Salem R et al: 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. 17(9):1425-39, 2006
                                    15. Salem R et al: Radioembolization with 90Yttrium Microspheres: a state-of-the-art bbachytherapy treatment for primary and secondary liver malignancies: part 1: technical and methodologic considerations. J Vasc Interv Radiol. 17(8):1251-78, 2006
                                    16. Geschwind JF et al: Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology. 127(5 Suppl 1):S194-205, 2004
                                    17. Sirspheres images
                                    Related Anatomy
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                                    Related Differential Diagnoses
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                                    References
                                    Tables

                                    Tables

                                    KEY FACTS

                                    • Terminology

                                      • Procedure

                                        • Post Procedure

                                          • Outcomes

                                            TERMINOLOGY

                                            • Definitions

                                              • Selective internal radiotherapy (SIRT) or radioembolization or transarterial radioembolization (TARE)
                                                • Anatomic & physiologic principles
                                                  • Most of normal liver parenchyma is supplied via portal vein (70-80%)
                                                  • Nearly all liver tumor supply is via the hepatic artery (90-100%)
                                                  • Therefore, intraarterial treatment will preferentially target tumor & spare normal live parenchyma
                                                • Yttrium-90 (⁹⁰Y) is pure β emitter (energetic electrons)
                                                  • Half-value layer is 2.5 mm; this means 50% of β particles are absorbed at every 2.5 mm of tissue penetration
                                                  • At 10 mm (4 half-value layers), nearly all (93.75%) β particles have been absorbed
                                                  • Small portion of β particle absorption (0.01%) is due to bremsstrahlung (breaking, decelerating), which results in γ radiation
                                                  • γ radiation has much longer half-value layer; therefore, treated patients do emit some γ radiation
                                                  • Half-life of ⁹⁰Y is 64 hours
                                                • Technical objective
                                                  • Deliver ⁹⁰Y-loaded particles throughout arterial bed of tumor
                                                  • Requires delivery of at least 120 Gy to tumor; less than 100 Gy appears to be ineffective
                                                • There are 2 commercially available ⁹⁰Y particles
                                                  • Resin microspheres with median diameter 30 μm (SIR-Spheres, Sirtex Medical; North Sydney, Australia)
                                                    • Lower radiation dose per particle (lower specific activity); therefore, significant embolization effect
                                                  • Glass microsphere median diameter 25 μm (TheraSphere, MDS Nordion; Ottowa, Canada)
                                                    • Higher radiation dose per particle (higher specific activity); therefore, little embolic effect
                                              • Pretreatment evaluation/shunt study
                                                • Angiogram of hepatic arterial supply
                                                  • (1) Define arterial supply to tumor & plan ⁹⁰Y delivery (split dose may be needed)
                                                  • (2) Embolize (if needed) arterial branches that may be at risk for inadvertent nontarget embolization
                                                    • Commonly gastroduodenal artery, falciform artery, left or right gastric artery
                                                  • (3) Calculate shunt ratio
                                                • Shunt study
                                                  • Injection of ⁹⁹mTc-MAA (macroaggregated albumin) via catheter in anticipated position of ⁹⁰Y treatment
                                                  • Followed by radionuclide lung-liver perfusion scan
                                                    • Calculate percent activity in lung over total activity (lung & liver)
                                                    • Shunt of < 15% is considered safe in patients with normal lung function
                                                    • If COPD or other lung disease, consider lowering acceptable shunt fraction (< 10%)
                                              • ⁹⁰Y microsphere administration
                                                • Usually performed within 2 weeks of pretreatment study
                                                • If > 6 months from shunt study, consider repeating shunt study as tumor hemodynamics may have changed

                                            PREPROCEDURE

                                            • Indications

                                              • Contraindications

                                                • Preprocedure Imaging

                                                  • Getting Started

                                                    • Radioactive Microspheres

                                                      PROCEDURE

                                                      • Patient Position/Location

                                                        • Equipment Preparation

                                                          • Procedure Steps

                                                            • Alternative Procedures/Therapies

                                                              POST PROCEDURE

                                                              • Things to Do

                                                                • Postprocedure Imaging/Follow-Up

                                                                  OUTCOMES

                                                                  • Complications

                                                                    • Expected Outcomes

                                                                      Selected References

                                                                      1. Biederman DM et al: Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein Invasion: resin versus glass microspheres. J Vasc Interv Radiol. 27(6):812-821.e2, 2016
                                                                      2. van Hazel GA et al: SIRFLOX: Randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 34(15):1723-31, 2016
                                                                      3. Njei B et al: Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 61(1):191-9, 2015
                                                                      4. Dutton SJ 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. 14:497, 2014
                                                                      5. Gibbs P et al: Selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 14:897, 2014
                                                                      6. Wang DS et al: Prophylactic topically applied ice to prevent cutaneous complications of nontarget chemoembolization and radioembolization. J Vasc Interv Radiol. 24(4):596-600, 2013
                                                                      7. Lau WY et al: Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys. 82(1):401-7, 2012
                                                                      8. Yaghmai V et al: Response to treatment series: part 2, tumor response assessment--using new and conventional criteria. AJR Am J Roentgenol. 197(1):18-27, 2011
                                                                      9. Lencioni R et al: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30(1):52-60, 2010
                                                                      10. Salem R et al: Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 138(1):52-64, 2010
                                                                      11. Ibrahim SM et al: Radiologic findings following Y90 radioembolization for primary liver malignancies. Abdom Imaging. 34(5):566-81, 2009
                                                                      12. Riaz A et al: Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J Vasc Interv Radiol. 20(9):1121-30; quiz 1131, 2009
                                                                      13. Shariff MI et al: Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 3(4):353-67, 2009
                                                                      14. Salem R et al: 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. 17(9):1425-39, 2006
                                                                      15. Salem R et al: Radioembolization with 90Yttrium Microspheres: a state-of-the-art bbachytherapy treatment for primary and secondary liver malignancies: part 1: technical and methodologic considerations. J Vasc Interv Radiol. 17(8):1251-78, 2006
                                                                      16. Geschwind JF et al: Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology. 127(5 Suppl 1):S194-205, 2004
                                                                      17. Sirspheres images