History and Evolution of Yttrium-90 Radioembolization for Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and affects millions worldwide. Due to the lack of effective systemic therapies for HCC, researchers have been investigating the use of locoregional tumor control with Yttrium-90 (Y90) radioembolization since the 1960s. Following the development of glass and resin Y90 microspheres in the early 1990s, Y90 radioembolization has been shown to be a safe and efficacious treatment for patients with HCC across Barcelona Clinic Liver Cancer (BCLC) stages. By demonstrating durable local control, good long term outcomes, and equivalent if not superior tumor responses and tolerability when compared to alternative therapies including transarterial chemoembolization (TACE) and sorafenib, Y90 radioembolization is being increasingly used in HCC treatment. More recently, investigations into variations in Y90 radioembolization technique including radiation segmentectomy and radiation lobectomy have further expanded its clinical utility. Here, we discuss the history and evolution of Y90 use in HCC. We outline key clinical trials that have established the safety and efficacy of Y90 radioembolization, and also summarize trials comparing its efficacy to existing HCC treatments. We conclude by reviewing the techniques of radiation segmentectomy and lobectomy, and by discussing dosimetry.

Keywords: HCC; Y90; Yttrium-90; hepatocellular carcinoma; liver cancer; radioembolization.

Figure 1

Barcelona Clinic Liver Cancer (BCLC) staging system and treatment algorithm The BCLC system provides treatment strategy in addition to prognostic outcomes by stage. Outcomes are expressed as median survival. ECOG PS = Eastern Cooperative Oncology Group Performance Status. * Patients with end-stage cirrhosis (i.e., Child-Pugh stage C, poor prognosis, or high Model for End-Stage Liver Disease (MELD) score). ^† First-line treatment with sorafenib or lenvatinib. Reproduced with permission from [6].

Figure 2

Radiation segmentectomy of HCC. (a) Angiogram of segmental tumor-supplying vessel (arrow) and tumor (arrowhead). (b) Pre-treatment MRI demonstrating arterial-enhancing tumor (arrowhead). (c) Post-treatment MRI showing radiation-induced changes in tumor-containing segment (arrows). Reproduced with permission from [43].

Figure 3

Pre- and post-treatment radiation lobectomy imaging. (A) Pre-treatment arterial phase contrast-enhanced CT showing multifocal right lobe HCC. Pre-treatment right and left HLVs are 644 and 498 mL, respectively. (B) Post-treatment contrast-enhanced CT demonstrates right lobe atrophy, tumor necrosis, and left lobe hypertrophy. Post-treatment HLVs are 185 mL and 776 mL, respectively. Reproduced with permission from [49].