Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases

Cancer (Impact Factor: 4.89). 09/2008; 113(5):921 - 929. DOI: 10.1002/cncr.23685
Source: PubMed


BACKGROUND.There are limited effective treatment options available and a poor 5-year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 (90Y) radioactive microspheres for patients with unresectable NETLMs.METHODS.Radioactive 90Y resin microspheres (selective internal radiation [SIR-Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7-day systemic infusion of 5-fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies.RESULTS.Thirty-four patients (22 men) with a mean age 61 years (range, 32-79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (±standard error) follow-up was 35.2 ± 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after 90Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 ± 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after 90Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months.CONCLUSIONS.In this open study of 34 patients, the results demonstrated that radioembolization with 90Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs. Cancer 2008. © 2008 American Cancer Society.

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    • "King et al. reported a series of 34 patients treated for NET metastasis with 22 patients (65%) experiencing complete response (CR), partial response (PR), or stable disease (SD) by RECIST criteria (3). One patient died within 1 month and the remaining 11 patients showed progressive disease by imaging. "
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    ABSTRACT: As a relatively safe outpatient procedure, radioembolization can potentially be used to treat any type of tumor within the liver, primary or metastatic. The safety and effectiveness of radioembolization in the treatment of hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC) has led many groups to explore its application in other malignancies. Moreover, other organs, such as the lungs and kidneys, have been explored as targets for therapy. Although the most data for radioembolization is related to HCC and mCRC, there is increasing experience and data regarding metastatic disease to the liver for other primary tumors. We review the current state of liver-directed therapy with radioembolization outside of HCC and mCRC, including metastatic neuroendocrine, breast, and melanoma, as well as limited experiences with other primary malignancies. Applications of radioembolization related to these other cancers and new trends and future directions will be discussed. With increasing use and availability of radioembolization, it promises to serve an expanding role in the repertoire of tools available for treating and managing oncologic disease.
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    • "(Jakobs 2008) Clinical manifestations of liver dysfunction were noted in 2 of 34 patients (6%) who developed jaundice following treatment with SIR-Spheres for metastatic neuroendocrine tumors in a series by King et al with a median follow up of 35.2 months, and clinical radiation hepatitis was noted in 1 of 46 patients (2%) treated with SIR-Spheres in a series by Lim et al with a median follow up of 9.8 months. (King 2008, Lim 2005) Previous studies have reported a wide range of the incidence of elevated liver function tests following treatment with SIR-Spheres, and our series lies well within the reported range of complications. Of note, of patients with an elevation "
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    ABSTRACT: The aim of this study was to estimate the incidence of complications after (90)Y microsphere radioembolization for unresectable hepatic tumors and evaluate risk factors for late complications. A cohort of 112 consecutive patients from two institutions underwent (90)Y microsphere radioembolization for unresectable hepatic tumors. Complications were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Symptoms secondary to postradioembolization syndrome occurring within 30 days were recorded as early complications, and all other complications were considered late complications. Seventy-eight patients (70%) experienced postradioembolization syndrome, including fatigue, abdominal pain, nausea, vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%) experienced clinically significant liver dysfunction; 13 patients (12%), 27 patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate aminotransferase, and alanine aminotransferase, respectively. Eleven patients (10%) experienced gastrointestinal ulceration, including two Grade 3 complications and one Grade 4 complication. Cholecystitis occurred in 7 patients (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1 patient (1%). No radiation pneumonitis was observed. The cumulative incidence of late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No Grade 5 toxicity occurred. (90)Y microsphere radioembolization is a well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade 3 or higher early or late toxicity.
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    • "The median survival from time of treatment was 70 months. Objective respond rate (complete and partial response) were observed in 50% of patients in a prospective studies, in which 32 patients were treated with 90Y microspheres [25]. "
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    ABSTRACT: Well-to-moderately differentiated neuroendocrine tumors of gastroesophageal and pancreatic origin (GEP-NETs) with liver metastasis are a heterogeneous group of malignancies for which a range of therapeutic options have been employed. Surgical resection of hepatic metastases or hepatic artery embolization may be beneficial in patients with hepatic-predominant metastatic disease. Patients with "carcinoid" syndrome and syndromes associated with functional pancreatic NET (PNET) can be effectively treated with somatostatin analogs. On the other hand, the efficacy of systemic chemotherapy for these patients is limited. A placebo-controlled, double-blind, prospective, and randomized study showed that octreotide LAR improves progression-free survival in patients with advanced midgut functional "carcinoids." In patients with advanced pancreatic NET, randomized, placebo-controlled studies have recently demonstrated that treatment with the tyrosine kinase inhibitor sunitinib or with mTOR inhibitor everolimus is associated with improved progression-free survival. Based on these studies, octreotide LAR, sunitinib, or everolimus are now considered as first-line therapeutic options in patients with advanced NET. Future studies will likely further define the role of these agents in patients with carcinoid liver metastasis and pancreatic NET liver metastasis.
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