Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio

BACKGROUND: Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres(® )Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment. METHODS: Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers. RESULTS: Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging. CONCLUSION: Doses up to 99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure. The lowest tumor dose producing a detectable response is 40.1 Gy. The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes

Chemical Durability of Y₂O₃-Al₂O₃-SiO₂ Glasses for the in Vivo Delivery of Beta Radiation

Microspheres made from Y2O3-Al2O3-SiO2 (YAS) glasses, which contain radioactive Y-90, are currently being used to treat liver cancer in humans, where their chemical durability is of prime importance. in deionized water or saline at 37 degrees C, the weight percent Yttrium (Y) dissolved from eight different YAS glasses ranged from only 0.02-0.13% of the total Y present and their dissolution rate was barely measurable, \u3c or = 1.0 x 10(-9) g/cm2-min. the most chemically durable YAS glass was 17Y2O3-19Al2O3-64SiO2, mol%. the small amount of Y released from microspheres, 25-35 microns diameter, of this glass after corrosion in saline or deionized water at 37 degrees C was essentially the same as for bulk glass samples. Based on their excellent chemical durability, it is concluded that YAS glass microspheres are suitable for in vivo use

Selective Internal Radiation Therapy with SIR-Spheres for the Treatment of Unresectable Colorectal Hepatic Metastases

The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level > 1.8 mg/dl and pulmonary shunt > 20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate