Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of death from cancer worldwide.¹ The incidence of HCC in the US is increasing because of the rise in the prevalence of hepatitis C virus infection.^2,3 HCC-related mortality is high because most cases are diagnosed at an advanced stage, when potentially curative therapies such as liver transplantation, surgical resection, and local ablation are not feasible.^4–7 The majority of patients are therefore candidates for palliative therapies only.⁸ Due to the capacity of liver cells to detoxify and excrete drugs, HCCs are relatively resistant to chemotherapy; in addition, the splenomegaly and cytopenias associated with cirrhosis with portal hypertension render patients prone to systemic chemotherapy-related toxicity.⁹ Transarterial chemoembolization (TACE) is a loco-regional therapy that delivers high doses of chemotherapy to HCCs through the hepatic artery, with limited systemic effect. TACE has been proven to improve survival of patients with unresectable HCC without portal vein thrombosis (PVT).^10–12 Recently, a number of devices for transarterial radioembolization (TARE) have been tested for treatment of HCC in early-phase studies. This article will summarize the results thus far, with an emphasis on yttrium-90 (90Y) radioactive glass microspheres, which are the only modality currently approved for use in the US.

Theoretical Considerations
The liver parenchyma is relatively sensitive to radiation, with a tolerance to external irradiation of approximately 30Gy.^13,14 In contrast, HCCs are relatively resistant to radiation, requiring doses of 120Gy for tumoricidal effect. The liver is unable to tolerate the radiation doses required to achieve tumoricidal effects by standard external-beam radiation; therefore, whole-liver external-beam radiation therapy is of limited utility in the treatment of unresectable HCC.¹⁵ Several studies have confirmed that focal radiation techniques employing a 3D approach instead of broad axial-plane techniques safely permit higher levels of radiation to targeted regions within the liver.^5,16 HCC tumors are highly vascular and receive almost all of their blood supply (95–100%) from the hepatic artery, in contrast to the normal liver parenchyma, which is primarily supplied by the portal vein (75–85%).¹⁵ Consequently, delivery of therapy through hepatic artery branches preferentially affects HCC tumors and spares the surrounding liver parenchyma. Selective targeting of radionuclides to tumors has been shown to achieve radiation dose ratios (tumor to benign liver) of up to 25–30 to 1.¹⁷

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