The technique of radioembolization is similar in many ways to any other embolization procedure (e.g. TACE), in that it involves catheter-based infusion of particles targeted at the arterial branch of the hepatic artery feeding the portion of the liver where the tumor is located. However, unlike chemoembolization, in which the mechanism of action of tumor necrosis is ischemia secondary to reduced blood flow, the mechanism of action in radioembolization is primarily due to radiation induced necrosis. Since radioembolization has minimal embolic effect, and won’t obstruct the blood supply to the functional liver, it is often considered the safer alternative to TACE for tumors with portal vein thrombosis.

There are two different radioisotopes used for radioembolization worldwide, Iodine-131[I-131]-labeled Lipiodol and Yttrium-90[Y90]-labeled microspheres. The former is not used in the USA due to lack of availability. The latter is available either as the glass Theraspheres or resin SIR-Spheres, with Theraspheres being the more common alternative in North America. Y90 is a β-emitter, with a half-life of 64 h, and maximum penetration of 11 mm in tissue. Typical prescription doses are in the range of 120–150 Gy, significantly higher than those possible with EBRT. According to the Radioembolization Brachytherapy Oncology Consortium Consensus Guidelines, Therasphere may be used in patients with unresectable primary HCC with liver-dominant tumor burden and life expectancy > 3 months [20]. Prior to treating a patient, it is important to do a 99^m-Tc macroaggregated albumin (MAA) scan to demonstrate that there is no shunting of blood flow to the lung or gastrointestinal tract that cannot be corrected by catheter techniques. The potential for ≥ 30 Gy radiation exposure to the lung is considered an absolute contraindication to radioembolization. Relative contraindications include a limited hepatic reserve, irreversibly elevated bilirubin and prior RT involving the liver.

The largest prospective trial evaluating Therasphere comes from Northwestern University [21]. 291 patients with HCC were treated, with response rates of 42 % using WHO criteria and 57 % using EASL criteria. The median TTP was 7.9 months for the entire cohort, and outcomes were strongly correlated with Child-Pugh score and the presence or absence of portal vein tumor thrombosis (PVTT). While Child-Pugh class A patients without PVTT could expect a median TTP of 15.5 months, Child-Pugh class B patients without PVTT had a median TTP of only 13 months. Median TTP was only 5.6–5.9 months for all patients with PVTT, regardless of Child-Pugh score. Complications of treatment most commonly involved a mild postembolization syndrome of fatigue, constitutional symptoms, and abdominal pain (20–55 %). Grade 3 or 4 elevation in bilirubin was seen in 19 % of patients, while the 30-day mortality was 3 % of patients.

Given the significant overlap in patient eligibility for radioembolization and chemoembolization, a randomized trial comparing the two was carried out in France, in which 142 patients with unresectable HCC were randomized to I-131-labeled Lipiodol or TACE [22]. In this study, the response rate and survival were similar in both arms at 1 and 3 years follow-up, however, there was significantly less toxicity in the radioembolization arm, with only 3 patients having severe side effects (as compared to 29 patients after chemoembolization). There are no randomized trials to date involving Therasphere, however, a recent comparative analysis published again by the group at Northwestern by Salem et al. suggests that radioembolization results in a better median TTP than TACE (13 vs. 8 months, respectively), again with less toxicity. There was no difference in median survival in the two groups [23]. It is important to note that in these studies, the chemoembolization groups were treated with the lipiodol technique (70 mg cisplatinum diluted in 140 mL of saline solution and 10 mL Lipiodol [22] and 30 mg mitomycin, 30 mg adriamycin and 100 mg cisplatin mixed with lipiodol [23]). The more recently introduced technique with drug-eluting beads has been shown to have lower toxicity, as discussed in Chap. 7c.

In summary, radioembolization is an emerging technology in the USA that may be better tolerated than TACE, with similar (if not somewhat improved) efficacy. It is also thought to be a safer alternative than TACE in patients with PVTT, but given the short median survival of these patients, it is unclear if they would benefit more from it than they would from systemic therapy alone. The expense of radioembolization also remains an issue, though may become less so if randomized data were to further clarify the optimal indications for, and benefit from its use. With respect to toxicity, trials comparing radioembolization with TACE with drug-eluting beads will be helpful.