The Evolving Role of Radioembolization in the Treatment of Neuroendocrine Liver Metastases

Abstract

At diagnosis, 21–50% of neuroendocrine tumors already have distant metastases, of which the liver is most commonly affected. Unfortunately, the presence of neuroendocrine liver metastases (NELM) is the most incriminating factor for survival. At NELM diagnosis, 60–70% of patients suffer from bilobar multifocal disease, making them ineligible for surgical resection. With limited systemic options, a clinical need for liver-directed treatments exists. Trans-arterial (bland) embolization, chemoembolization and radioembolization have been increasingly used in the treatment of NELM. In recent years, radioembolization (also known as selective internal radiation therapy) has gained attention due to promising tumor reductive results, limited toxicities and increasing scientific evidence. This review provides basic insights into radioembolization as a technique, a summary of available literature on radioembolization in NELM, and discusses caveats, challenges and new insights when considering radioembolization in NELM.

Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors

“…NET liver lesions are generally hypervascular, causing preferential arterial flow towards tumors. This characteristic causes microspheres to lodge in tumor arterioles, ensuring high tumor accumulation of the infused microspheres, while relatively sparing normal liver parenchyma from irradiation [ 32 ]. Currently, three commercially available radioactive microspheres are used for radioembolization: 90 Y-labeled glass spheres (Theraspheres, Boston Scientific), 90 Y-labeled resin spheres (SirSpheres, SIRTex), and 166 Holmium ( 166 Ho)-labeled PLLA-MS spheres (QuiremSpheres, Quirem Medical).…”

“…Currently, three commercially available radioactive microspheres are used for radioembolization: 90 Y-labeled glass spheres (Theraspheres, Boston Scientific), 90 Y-labeled resin spheres (SirSpheres, SIRTex), and 166 Holmium ( 166 Ho)-labeled PLLA-MS spheres (QuiremSpheres, Quirem Medical). The entire work-up for radioembolization is beyond the scope of this review but has previously been explained [ 32 ].…”

Radioembolisation of liver metastases

“…Recent prospective registry data and pooled data from published retrospective studies show SIRT can be safely used as an alternative or salvage therapy for NELM, including patients who have undergone surgical resection, multiple prior systemic and arterial therapies, and for relief of symptoms of carcinoid syndrome, with median survival 28-33 months. 2,41,59 Median OS was 33 months in both the CIRT and RESiN registries. In the RESiN registry, well-differentiated tumours had a median OS of 41 months, compared to 13 and 25 months for moderate-and poorly differentiated tumours, respectively.…”

“…A few small studies are available with SIRT in second-line setting or combined with systemic or targeted treatment in aggressive or liver-dominant disease. 59 Delayed hepatotoxicity from NELM treated with TACE and SIRT have been reported from 6 months to several years following treatment. TACE-related toxicities on average were less severe and manifested primarily as laboratory derangements in one study, whilst SIRT toxicities included clinical hepatic decompensation.…”

“…Survival was higher for patients with carcinoid, pancreatic NETs and lower for grade III NET. A few small studies are available with SIRT in second‐line setting or combined with systemic or targeted treatment in aggressive or liver‐dominant disease 59 …”