Treatment of Hepatocellular Carcinoma by Radioembolization Using ⁹⁰Y Microspheres

Abstract

The use of external beam radiation therapy for primary treatment of hepatocellular carcinoma (HCC) has been limited by the low radiation tolerance of the non-tumoral liver. However, technical advances allowing partial liver volume external irradiation have resulted in consistently high response rates. Internal radiation therapy, also called ⁹⁰Y radioembolization (⁹⁰Y-RE), consists in delivering implantable microspheres labeled with ⁹⁰Y into the arteries that feed liver tumors in order to provide a high dose of radiation to tumor nodules irrespective of their number, size and location, while preserving the non-tumoral liver tissue from receiving a harmful level of radiation. Among patients with HCC, ⁹⁰Y-RE is used for those that have a preserved liver function and unresectable tumors that cannot be treated with percutaneous ablation. Although ⁹⁰Y-RE is by and large well tolerated, it may produce relevant toxic effects as a result of radiation of non-target organs including cholecystitis, gastrointestinal ulceration, pneumonitis, and most importantly, liver toxicity. A significant effect on tumor growth in the treated lesions is consistently observed with disease control rates in excess of 80%. Also, ⁹⁰Y-RE may allow downstaging large or multiple lesions to radical treatments with curative intent. When compared with the survival of HCC patients in advanced stage either not treated or treated with ineffective systemic agents, survival after ⁹⁰Y-RE is encouraging and warrants future clinical trials. Clinical research in combining the cytotoxic effect of ⁹⁰Y with the cytostatic mechanism of targeted therapies is currently in progress and will provide valuable safety and toxicity data that may translate into improved clinical outcome and overall survival.

Hepatocellular Carcinoma: Focus on Different Aspects of Management

“…It can be used as bridge to RFA and resection. Comparison between the survival of HCC patients in advanced stage either not treated or treated with ineffective systemic agents, survival after (90)Y-RE is encouraging and warrants future clinical trials [122–125]. …”

Preparation of 177Lu-Labeled Oxine in Lipiodol as a Possible Agent for Therapy of Hepatocellular Carcinoma: A Preliminary Animal Study

“…In one approach the therapeutic isotope is incorporated into nonbiodegradable or very slowly degrading particulates of several microns in diameter, which get localized in the capillaries, for example, 90 Y-labeled glass microspheres. 5 Alternatively, the radioactivity is incorporated into a strongly lipophilic preparation, which permeates through the hepatocellular tissue and is retained there to deliver the therapeutic dose. A well-known example of this is 131 I-labeled lipiodol.…”

Radioembolization: Concepts and Procedures

“…Mild to moderate lymphopenia is usually seen after Y-90 RE but not associated with increased susceptibility to infection (Carr 2004). However, although RE is well tolerated, it may produce relevant toxic effects as a result of radiation of non-target organs including cholecystitis, gastrointestinal ulceration, pneumonitis, and most importantly for patients with chronic liver disease, liver toxicity (Nicolay et al 2009;Sangro et al 2009;Riaz et al 2009). Liver damage after Y-90 RE typically emerges 4-8 weeks after microsphere injection as jaundice, mild ascites and a moderate increase in GGTP and alkaline phosphatase, with mild or absent changes in transaminases .…”

“…The radioactive sources are not implanted directly into the tumor tissue but rather injected into the arteries feeding the tumors (Sangro et al 2009). …”