HCC Radioembolization with Yttrium-90 Polymer Beads (SIR-Spheres)

Abstract

Introduction: Transarterial radioembolization (TARE) is a form of brachytherapy in which microspheres loaded with the radioactive isotope yttrium-90 (⁹⁰Y) are injected selectively to the tumor-feeding arteries through a catheter using fluoroscopic guidance. The use of ⁹⁰Y microspheres leads to tumor necrosis by delivering a high radiation dose (>70 Gy, tumoricidal threshold) directly to HCC nodules, sparing the non-tumoral liver, and with little or no embolic effect on the vessels. Resin ⁹⁰Y microspheres are 20–60 μm in size, carry approximately 50 Bq/sphere, and contain 40–80 million microspheres per 3 GBq (1 vial).

Indications: TARE is a suitable first-line therapy for intermediate-stage patients with locally advanced disease and those who are poor candidates for transarterial chemoembolization (TACE). Surgery and thermal ablation are precluded due to lesion size or amount. TARE is a valid treatment option also for patients with HCC and portal vein tumor thrombosis (PVTT), which is commonly recognized as a relative contraindication to other transarterial therapies.

Selection Criteria: To be considered for TARE, patients with HCC should have liver-only or liver-dominant disease, a life expectancy >12 weeks, and ECOG performance status <2 or Karnofsky performance index ≥60%. Preserved liver function is essential. Kidney function and blood coagulation are other important parameters to assess.

Administration: The majority of TAREs are performed by calculating the injected activity based on empiric formulas suggested by the manufac turers instead of following a scrupulous dosimetric algorithm. Three methods of activity estimation are suggested in the manufacturer’s user manual for resin microspheres: body surface area (BSA), empiric, and partition.

Pre-TARE Imaging: HCC can be evaluated through different techniques: US, contrast-enhanced CT, and contrast-enhanced MRI (gold standard for HCC nodules).

Treatment Procedure: All patients scheduled for TARE have to undergo initial hepatic and gastrointestinal angiography to evaluate the amount of resin microspheres that could inadvertently pass from the artery site of injection to the systemic blood circulation. During angiography, contrast media is administered intra-arterially followed by administration of 150 MBq of ^99mtechnetium-labeled macroaggregated albumin (⁹⁹Tc; eluted in 5 mL of saline; ⁹⁹Tc-MAA) at the same site. The ⁹⁹Tc-MAA microparticles act as good surrogate for ⁹⁰Y resin microspheres due to the similarities in average diameter and density. One hour after administration of ⁹⁹Tc, a SPECT is performed in order to assess the percentage of radioactive spheres shunted to the systemic circulation, particularly to the lungs and extrahepatic abdominal organs. Patients may undergo TARE only if <20% of ⁹⁹TC albumin macroaggregates are shunted to the lungs and if the ⁹⁰Y dose does not exceed 30 Gy in single administration or 50 Gy in cumulative doses for all planned infusions. TARE is then performed retracing the tumor-feeding arteries and administering the ⁹⁰Y resin microspheres.

Follow-up: Follow-up comprises a complete liver function test, a complete blood count, tumor marker analysis, and contrast-enhanced CT 40 or 60 days after TARE.

Post-procedural Assessments: Radionecrosis is demonstrated by a hypointense area with absence of contrast enhancement on CT. Response is classified according to modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Adverse Events: The most common adverse event experienced by patients following TARE is postembolization syndrome (PES), which encompasses symptoms of nausea, vomiting, fatigue, fever, and mild abdominal pain, especially in the right hypochondrium. Rare but serious complications of TARE have been reported and include gastrointestinal ulceration/bleeding, cholecystitis, pancreatitis, and radiation pneumonitis.

Conclusions: To summarize, TARE is a well-tolerated procedure that shows comparable or better outcomes and toxicities to those reported for other intra-arterial therapies.