Transarterial radioembolization using yttrium-90 microspheres in the treatment of hepatocellular carcinoma: a review on clinical utility and developments

Abstract

A selective intra-arterial liver injection using yttrium-90-loaded microspheres as sources for internal radiation therapy is a form of transarterial radioembolization (TARE). Current data from the literature suggest that TARE is effective in hepatocellular carcinoma (HCC) and is associated with a low rate of adverse events; however, they are all based on retrospective series or non-controlled prospective studies, since randomized controlled trials comparing the other liver-directed therapies for intermediate and locally advanced stages HCC are still ongoing. The available data show that TARE provides similar or even better survival rates. TARE is very well tolerated and has a low rate of complications; these complications do not result from the embolic effects but mainly from the unintended irradiation to non-target tissue, including the liver parenchyma. The complications can be further reduced by accurate patient selection and a strict pre-treatment evaluation, including dosimetry and assessment of the vascular anatomy. First-line TARE is best indicated for intermediate-stage patients (according to the Barcelona Clinic Liver Cancer [BCLC] staging classification) who are poor candidates for transarterial chemoembolization or patients having locally advanced disease with segmental or lobar branch portal vein thrombosis. Moreover, data are emerging regarding the use of TARE in patients classified slightly above the criteria for liver transplantation with the purpose of downstaging them. TARE can also be applied as a second-line treatment in patients progressing to transarterial chemoembolization or sorafenib; a large number of Phase II/III trials are in progress in order to evaluate the best association with systemic therapies. Given the complexity of a correct treatment algorithm for potential TARE candidates and the need for clinical guidance, a comprehensive review was carried out analyzing both the best selection criteria of patients who really benefit from TARE and the new advances of this therapy which add significant value to the therapeutic weaponry against HCC.

Keywords: hepatocellular carcinoma; radioembolization; yttrium-90.

Figure 1

(A–D) The pretreatment angiogram. Notes: (A) The hepatofugal flow through a small falciform artery (arrow). (B) The ^99mTc-MAA and (C) the SPECT images confirmed the extrahepatic distribution of the microspheres (arrows). (D) The falciform artery was superselectively catheterized and embolized with coils (arrow). Abbreviations: ^99mTc-MAA, ^99mTc labeled macroaggregated albumin; SPECT, single photon emission computed tomography.

Figure 2

(A and B) The pretreatment angiogram. Notes: (A) This shows a very thin retroduodenal hepatic artery (arrow). (B) Superselective catheterization of the retroduodenal artery and embolization with microcoils.

Figure 3

(A–G) Large HCC of segment I as shown on CT. Notes: (A) During the arterial and (B) the portal-venous phase, further confirmed at (C) angiography. (D) Superselective TARE treatment. (E) At a 6-month follow-up, showing the significant volume decrease of the target lesion (circle in E) best seen in the portal-venous phase (F) with the appearance of a minimally viable tumor (arrow) further treated with conventional can also be applied as a second-line treatment in patients progressing TACE with a complete uptake of Lipiodol (G). Abbreviations: HCC, hepatocellular carcinoma; CT, computed tomography; TARE, transarterial radioembolization; TACE, transarterial chemoembolization.

Figure 4

(A–F) Bilobar HCC of the right hepatic lobe (V–VIII segments). Notes: (A) The pretreatment CT shows hypervascularization of the larger lesion in the arterial phase and (B) the hypoattenuation of both nodules in the portal-venous phase. (C) The pretreatment angiogram confirms the large HCC nodule of the dome of the liver. CT study performed 8 months after treatment shows the complete devascularization of the lesions. Note the capsular retraction of the treated segment as a consequence of hepatic fibrosis (arrows) and the transient perfusion abnormalities in the treated area, persistent in both (D) the arterial and (E) the portal-venous phase which is, however, not a recurrent tumor. (F) Of note, the compensatory hypertrophy of the left lobe. Abbreviations: HCC, hepatocellular carcinoma; CT, computed tomography.

Figure 5

Graph of median survival (in months) according to BCLC stages and PVTT reported by the different series. Abbreviations: HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; PVTT, portal vein tumor thrombosis.