The liver is the primary site of metastases in colorectal cancer (CRC) because most the venous mesenteric drainage enters the hepatic portal venous circulation. More than 50% of patients with CRC will develop hepatic metastases over the course of their life. This ultimately leads to death more than two-thirds of these patients.

Surgery is curative in only 20% of patients, and 70% will develop recurrence, even when combined with systemic therapy. Yet it remains the main therapeutic option.

When surgery is not possible, e.g., non-resectable disease or patients unfit for it—other ablative methods have been developed in the last decades including radiofrequency ablation. The latter can prolong the overall survival, with or without surgery and chemotherapy, in patients with colorectal liver metastases.

Although systemic chemotherapy has largely improved outcome with the development of modern chemotherapy agents and biologics, the response rates and overall survival gains remain rather disappointing. For this reason, efforts to seek alternative treatments remain one of the primary aims of the research.

Radiation-based therapy

Furthermore, to reduce the burden of toxicity of chemotherapy and to maximize its therapeutic effects, more targeted and selective locoregional approaches have been developed. Among these are hepatic arterial infusion (HAI) and radiation-based therapy.

HAI therapy is a locoregional treatment based on the delivery of the chemotherapeutic agent through the hepatic arterial circulation. This provides high local drug concentrations with the goal of minimizing systemic toxicity.

Among the various agents studied, floxuridine is a good candidate for HAI because it has a short half-life (<10 min) and more than 90% hepatic extraction, resulting in a 16-fold higher concentration in liver metastases compared with venous administration.

Some prospective trials have investigated using HAI alone, but other studies showed best survival benefits in multimodality treatment: properly selected patients with CRC liver metastases can achieve a 5-year survival benefit as high as 78% with hepatic resection followed by adjuvant systemic therapy plus HAI.

However, treatment with HAI could have side effects that need to be balanced with the survival benefit, particularly, the risk of biliary sclerosis in less than 5% of patients. As regards radiation-based therapies, external beam radiation has not found a defined place in the management of liver tumors because of the high risk of fatal hepatitis based on veno-occlusive mechanism.

Selective internal radiotherapy with Yttrium-90 resin microspheres consists of delivering β-emitter microspheres into the arterial supply of the liver under fluoroscopic guidance.

The delivery of the resin microspheres into branches of the hepatic artery—which supplies most blood to liver tumours—results in selective targeting by high-dose radiotherapy. This happens because the healthy liver is supplied predominantly by the portal venous system and therefore relatively spared from radiation exposure.

Yttrium-90 is a high-energy, pure β-emitter with a half-life of 64 hours and maximum tissue penetration of 11 mm, which makes it very suitable for treatment of liver tumors. Yttrium-90 is relatively straightforward to use, with limited issues relating to radioprotection for the patient, family or attending staff.

The microspheres are approximately 35 µm in diameter, which means they are permanently entrapped at the arteriolar end of the capillary bed. The technique provides that any arteriovenous shunting through the liver or the tumor is assessed before selective internal radiotherapy (SIRT) is performed.