DOI: 10.1148/rg.25si055515
Yttrium-90 Microsphere Therapy for Hepatic Malignancy: Devices, Indications, Technical Considerations, and Potential Complications1
Ravi Murthy, MD,
Rodolfo Nunez, MD,
Janio Szklaruk, MD,
William Erwin, PhD,
David C. Madoff, MD,
Sanjay Gupta, MD,
Kamran Ahrar, MD,
Michael J. Wallace, MD,
Alan Cohen, MD,
Douglas M. Coldwell, PhD, MD2,
Andrew S. Kennedy, MD and
Marshall E. Hicks, MD
1 From the Interventional Radiology Section (R.M., D.C.M., S.G., K.A., M.J.W., M.E.H.) and the Departments of Nuclear Medicine (R.N.), Body Imaging (J.S.), and Imaging Physics (W.E.), Division of Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 325, Houston, TX 77030; Department of Radiology and Nuclear Medicine, University of Texas Hermann Hospital, Houston, Tex (A.C.); Department of Radiology, University of Mississippi Medical Center, Jackson, Miss (D.M.C.); and Wake Radiation Oncology, Cary, NC (A.S.K.). Presented as an education exhibit at the 2004 RSNA Annual Meeting. Received March 23, 2005; revision requested April 25 and received June 7; accepted June 15. The article discusses an investigational or unlabeled use of a commercial device or pharmaceutical that has not been approved for such purpose by the FDA. The glass microsphere device (TheraSphere; MDS Nordion, Ottawa, Ontario, Canada) has received humanitarian device exemption approval from the FDA for treatment of unresectable hepatocellular carcinoma and can be used only with investigational review board oversight. The resin microsphere device (SIR-Spheres; Sirtex Medical, Lake Forest, Ill) has received premarket approval from the FDA for use in combination with hepatic arterial floxuridine therapy to treat colorectal metastasis to the liver; its use in any other manner for treatment of hepatic neoplastic disease is an off-label application. R.M., A.S.K., and D.M.C. have received honoraria from Sirtex Medical; all remaining authors have no financial relationships to disclose.
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Figure 1. Photomicrograph (original magnification, x 200) shows glass microspheres.
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Figure 2. Photomicrograph (original magnification, x 1000) shows resin microspheres.
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Figure 3a. Images obtained for therapy planning show normal anatomy in a 69-year-old man. (a) Celiac arteriogram obtained before treatment shows gastroduodenal artery (arrowhead), right gastric artery (white arrow), and hepatic artery branches (black arrows). Note that the right hepatic artery arises early in the branching of the common hepatic artery, before the origin of the gastroduodenal artery. (b, c) Arteriograms show selective catheterization and coil embolization of the right gastric artery (arrow in b) and gastroduodenal artery (arrow in c) to avert reflux and thereby decrease the risk of gastric ulcer. (d) Indirect portal venogram depicts patency of the main (arrow), left, and right portal venous branches.
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Figure 3b. Images obtained for therapy planning show normal anatomy in a 69-year-old man. (a) Celiac arteriogram obtained before treatment shows gastroduodenal artery (arrowhead), right gastric artery (white arrow), and hepatic artery branches (black arrows). Note that the right hepatic artery arises early in the branching of the common hepatic artery, before the origin of the gastroduodenal artery. (b, c) Arteriograms show selective catheterization and coil embolization of the right gastric artery (arrow in b) and gastroduodenal artery (arrow in c) to avert reflux and thereby decrease the risk of gastric ulcer. (d) Indirect portal venogram depicts patency of the main (arrow), left, and right portal venous branches.
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Figure 3c. Images obtained for therapy planning show normal anatomy in a 69-year-old man. (a) Celiac arteriogram obtained before treatment shows gastroduodenal artery (arrowhead), right gastric artery (white arrow), and hepatic artery branches (black arrows). Note that the right hepatic artery arises early in the branching of the common hepatic artery, before the origin of the gastroduodenal artery. (b, c) Arteriograms show selective catheterization and coil embolization of the right gastric artery (arrow in b) and gastroduodenal artery (arrow in c) to avert reflux and thereby decrease the risk of gastric ulcer. (d) Indirect portal venogram depicts patency of the main (arrow), left, and right portal venous branches.
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Figure 3d. Images obtained for therapy planning show normal anatomy in a 69-year-old man. (a) Celiac arteriogram obtained before treatment shows gastroduodenal artery (arrowhead), right gastric artery (white arrow), and hepatic artery branches (black arrows). Note that the right hepatic artery arises early in the branching of the common hepatic artery, before the origin of the gastroduodenal artery. (b, c) Arteriograms show selective catheterization and coil embolization of the right gastric artery (arrow in b) and gastroduodenal artery (arrow in c) to avert reflux and thereby decrease the risk of gastric ulcer. (d) Indirect portal venogram depicts patency of the main (arrow), left, and right portal venous branches.
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Figure 4a. Images obtained for therapy planning show common anatomic variations in a 42-year-old man with bilo-bar disease, findings that resulted in alteration of the treatment plan. (a) Celiac arteriogram depicts an accessory left hepatic artery (curved arrow), which originates from the left gastric artery (straight arrow), and the splenic and common hepatic arteries (arrowheads). (b) Superior mesenteric arteriogram shows a replacement of the right hepatic artery (arrowhead) and a normal left hepatic artery (arrow). Embolization of the accessory left hepatic artery was necessary to augment intrahepatic collateral flow before treatment. A single transarterial infusion of 90Y microspheres was then administered via the proper hepatic artery to treat the entire liver.
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Figure 4b. Images obtained for therapy planning show common anatomic variations in a 42-year-old man with bilo-bar disease, findings that resulted in alteration of the treatment plan. (a) Celiac arteriogram depicts an accessory left hepatic artery (curved arrow), which originates from the left gastric artery (straight arrow), and the splenic and common hepatic arteries (arrowheads). (b) Superior mesenteric arteriogram shows a replacement of the right hepatic artery (arrowhead) and a normal left hepatic artery (arrow). Embolization of the accessory left hepatic artery was necessary to augment intrahepatic collateral flow before treatment. A single transarterial infusion of 90Y microspheres was then administered via the proper hepatic artery to treat the entire liver.
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Figure 5. Scintigraphy performed for treatment planning in a 54-year-old man with metastasis of neuroendocrine cancer to the liver. Planar scintigram obtained after hepatic arterial injection of 5 mCi (185 MBq) of 99mTc-labeled MAA shows radionuclide activity in regions of interest in the liver and lungs but not in the gastrointestinal region. The hepatopulmonary shunt fraction, calculated on the basis of scintigraphic findings, was 10.2%, and the patient therefore underwent treatment with 90Y resin microspheres at a reduced dose. Treatment was successful.
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Figure 6. Photograph shows the infusion set used with the glass microsphere device. The radioactive microspheres are suspended in normal saline in a vial that is shielded by a lead pig (curved black arrow) adjacent to a separate venting vial inside another lead pig. The suspension is administered with high-pressure infusion by using an inflation device (straight black arrow) to agitate and disperse the microspheres via the efferent tubing into the catheter (white arrow).
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Figure 7. Photograph shows the infusion set used with the resin microsphere device. The radioactive microspheres are suspended in sterile water inside a vial (curved black arrow) that is housed in a shielded container (straight black arrow). A three-way stopcock (white arrow) allows sequential infusion of the 90Y microspheres and contrast material injection for monitoring the progress of infusion.
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Figure 8. Bremsstrahlung imaging helps confirm successful targeting of hepatic metastases from pancreatic islet cell tumor in a 54-year-old man. Representative axial, coronal, and sagittal CT images (first column), SPECT images (second column), and SPECT/CT fusion images (third column) obtained with a dual-modality imaging system (Hawkeye; GE Medical Systems, Milwaukee, Wis) show selective activity in the right hepatic lobe approximately 24 hours after intraarterial infusion of 90Y-bearing resin microspheres at a dose of 55 mCi (2035 MBq).
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Figure 9a. Complete response to brachytherapy with use of the resin microsphere device as an adjunct to systemic chemotherapy. Axial contrast-enhanced CT scans show numerous low-attenuation hepatic metastases before treatment (a) and absence of metastases 15 months after treatment (b). (Courtesy of Bruce Gray, MD, Sirtex Medical, Australia.)
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Figure 9b. Complete response to brachytherapy with use of the resin microsphere device as an adjunct to systemic chemotherapy. Axial contrast-enhanced CT scans show numerous low-attenuation hepatic metastases before treatment (a) and absence of metastases 15 months after treatment (b). (Courtesy of Bruce Gray, MD, Sirtex Medical, Australia.)
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Figure 10a. Radiation-induced change in appearance of liver parenchyma on axial contrast-enhanced CT images in a 49-year-old woman who underwent treatment with the glass microsphere device for metastatic neuroendocrine cancer. (a) Image obtained before treatment shows low-attenuation regions consistent with metastases to the liver. (b) Image obtained 3 months after treatment shows areas with low attenuation (arrows) in the liver parenchyma adjacent to the metastases. Low attenuation in this case was treatment related but could be erroneously interpreted as evidence of disease progression. (Courtesy of Barry Daly, MD, University of Maryland, Baltimore, Md.)
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Figure 10b. Radiation-induced change in appearance of liver parenchyma on axial contrast-enhanced CT images in a 49-year-old woman who underwent treatment with the glass microsphere device for metastatic neuroendocrine cancer. (a) Image obtained before treatment shows low-attenuation regions consistent with metastases to the liver. (b) Image obtained 3 months after treatment shows areas with low attenuation (arrows) in the liver parenchyma adjacent to the metastases. Low attenuation in this case was treatment related but could be erroneously interpreted as evidence of disease progression. (Courtesy of Barry Daly, MD, University of Maryland, Baltimore, Md.)
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Figure 11a. Representative coronal images from two fluorine 18 fluorodeoxyglucose whole-body PET examinations performed 6 months apart in a 55-year-old man who was undergoing systemic chemotherapy for metastatic colorectal cancer. (a) Initial scan shows extensive hepatic metastases. (b) Follow-up scan obtained after liver-directed therapy with the resin microsphere device shows a marked decrease in metabolic activity in the metastatic hepatic lesions but increased metabolic activity at sites in the sternum, lungs, and left side of the groin. Local tumor control was achieved, but systemic therapy failed.
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Figure 11b. Representative coronal images from two fluorine 18 fluorodeoxyglucose whole-body PET examinations performed 6 months apart in a 55-year-old man who was undergoing systemic chemotherapy for metastatic colorectal cancer. (a) Initial scan shows extensive hepatic metastases. (b) Follow-up scan obtained after liver-directed therapy with the resin microsphere device shows a marked decrease in metabolic activity in the metastatic hepatic lesions but increased metabolic activity at sites in the sternum, lungs, and left side of the groin. Local tumor control was achieved, but systemic therapy failed.
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Figure 12. Cholecystitis and perforated duodenal ulcer in a 43-year-old man who underwent four treatments with the glass microsphere device for hepatic metastasis from colorectal cancer. Photomicrograph of a gallbladder specimen (hematoxylineosin stain; original magnification, x40) obtained at cholecystectomy performed during exploratory laparotomy shows glass microspheres (arrows) in the Rokitansky-Aschoff sinuses, with associated inflammation in the gallbladder wall and ulcerated duodenum.
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Figure 13a. Gastric ulcer in a 67-year-old man who underwent treatment with the resin microsphere device for metastatic colorectal cancer. Ulceration occurred despite prior coil embolization of the gastroduodenal artery. (a, b) Images obtained at common hepatic arteriography show a prominent gastroduodenal artery (black arrow) and a right gastric artery (white arrow) that originates from the proximal portion of the left hepatic artery (black arrowhead), a common anatomic variant. Because of the variant anatomy, infusion via the proper hepatic artery resulted in resin microsphere deposition and consequent ulceration in the stomach. (c) Photomicrograph (hematoxylineosin stain; original magnification, x200) of a gastric biopsy specimen shows staining of resin microspheres (arrows) in the submucosa, with associated eosinophil infiltration.
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Figure 13b. Gastric ulcer in a 67-year-old man who underwent treatment with the resin microsphere device for metastatic colorectal cancer. Ulceration occurred despite prior coil embolization of the gastroduodenal artery. (a, b) Images obtained at common hepatic arteriography show a prominent gastroduodenal artery (black arrow) and a right gastric artery (white arrow) that originates from the proximal portion of the left hepatic artery (black arrowhead), a common anatomic variant. Because of the variant anatomy, infusion via the proper hepatic artery resulted in resin microsphere deposition and consequent ulceration in the stomach. (c) Photomicrograph (hematoxylineosin stain; original magnification, x200) of a gastric biopsy specimen shows staining of resin microspheres (arrows) in the submucosa, with associated eosinophil infiltration.
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Figure 13c. Gastric ulcer in a 67-year-old man who underwent treatment with the resin microsphere device for metastatic colorectal cancer. Ulceration occurred despite prior coil embolization of the gastroduodenal artery. (a, b) Images obtained at common hepatic arteriography show a prominent gastroduodenal artery (black arrow) and a right gastric artery (white arrow) that originates from the proximal portion of the left hepatic artery (black arrowhead), a common anatomic variant. Because of the variant anatomy, infusion via the proper hepatic artery resulted in resin microsphere deposition and consequent ulceration in the stomach. (c) Photomicrograph (hematoxylineosin stain; original magnification, x200) of a gastric biopsy specimen shows staining of resin microspheres (arrows) in the submucosa, with associated eosinophil infiltration.
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Figure 14a. Radiation-induced liver disease in a 44-year-old woman who underwent treatment for bilobar cholangiocarcinoma with 90Y-bearing resin microspheres at a total radiation dose of 50.1 mCi (1853.7 MBq). Although the blood level of CA 19–9 antigen decreased from 980.2 to 408.2 U/mL after treatment, the patient developed worsening symptoms of hepatic decompensation. (a) Axial contrast-enhanced CT scan of the liver, obtained 4 weeks after treatment, shows ascites (arrow). (b) Photomicrograph (hematoxylineosin stain; original magnification, x200) of a liver biopsy specimen obtained for histopathologic analysis depicts hepatocyte swelling, mild microvesicular steatosis (black arrows), and a resin microsphere (white arrow) without any associated inflammatory response.
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Figure 14b. Radiation-induced liver disease in a 44-year-old woman who underwent treatment for bilobar cholangiocarcinoma with 90Y-bearing resin microspheres at a total radiation dose of 50.1 mCi (1853.7 MBq). Although the blood level of CA 19–9 antigen decreased from 980.2 to 408.2 U/mL after treatment, the patient developed worsening symptoms of hepatic decompensation. (a) Axial contrast-enhanced CT scan of the liver, obtained 4 weeks after treatment, shows ascites (arrow). (b) Photomicrograph (hematoxylineosin stain; original magnification, x200) of a liver biopsy specimen obtained for histopathologic analysis depicts hepatocyte swelling, mild microvesicular steatosis (black arrows), and a resin microsphere (white arrow) without any associated inflammatory response.
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Copyright © 2005 by the Radiological Society of North America.
