Y-90 Radiomicrosphere Therapy: Principles and Clinical Use in Colorectal Cancer Liver Metastases

Y-90 radiomicrosphere therapy (Y-90) is a liver-directed therapy, utilizing the hepatic tumor neovasculature as a venue of delivery of an internal mode of radiation. Y-90 regional microsphere therapy (RMT) is performed via arterial administration of Y-90. Yittrium-90 (Y-90) is a high-energy beta particle-radiating radioisotope, which is incorporated in biocompatible microspheres measuring 30–40 microns. The intellectual basis of Y-90 radiomicrosphere treatment is the preferential distribution of microspheres, when injected hepatic arterially, yielding much higher concentrations in the tumor compartment than the normal liver parenchyma. The first report of Y-90 microsphere treatment in patients with colorectal cancer liver metastases (CRCLM) was performed in the early 1960s by Irving Ariel, a New York surgeon, and developed as a mature FDA-approved modality by Bruce Gray, another surgeon from Australia. The technique today is optimally used with multidisciplinary collaboration and coordination between a nuclear medicine physician and an interventional radiologist. The treatment planning involves depiction of the hepatic vascular anatomy, target field of treatment coverage, and internal radiation dosimetry to determine the administered activity to achieve maximum therapeutic profile, maximizing tumor lethality and minimizing liver toxicity. The potential adverse events including radiomicrosphere-induced liver disease resulting from excessive liver absorbed dose, radiation pneumonitis due to hepatico-pulmonary shunting of radiomicrospheres, and gastroduodenitis associated with reflux of the radiomicrospheres into the gastric or gastroduodenal arteries can easily be prevented by careful treatment planning. Overall, the modality has proven to be a safe and effective treatment in expert hands. A number of well-designed clinical trials as well as large retrospective analyses demonstrated the efficacy of Y-90 RMT in patients with colorectal cancer liver metastases. The Y-90 RMT can be administered as stand-alone treatment in liver-only or liver-predominant advanced disease, or it can be combined with chemotherapy in a front-line setting in early metastatic disease. It also can be used to achieve tumor downsizing and induction of future liver remnant hyperplasia in a neoadjuvant setting.