Sustained safety and efficacy of extended-shelf-life ⁹⁰Y glass microspheres: Long-term follow-up in a 134-patient cohort

Purpose: To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life ⁹⁰Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. Methods: Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life ⁹⁰Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectively captured and categorized according to the Common Terminology Criteria. Response in the index lesion was assessed using WHO and EASL guidelines. Results: The mean delivered radiation dose was 123 Gy to the target liver tissue. The mean increase in number of microspheres with this approach compared to standard ⁹⁰Y glass microsphere dosimetry was 103 %, corresponding to an increase from 3.84 to 7.78 million microspheres. Clinical toxicities included fatigue (89 patients, 66 %), abdominal pain (49 patients, 36.6 %), and nausea/vomiting (25 patients, 18.7 %). Grade 3/4 bilirubin toxicity was seen in three patients (2 %). Two (1 %) of the initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers were not seen in any of the subsequent 84 patients. According to WHO and EASL guidelines, response rates were 48 % and 57 %, respectively, and 21 % demonstrated a complete EASL response. Conclusion: This study showed sustained safety and efficacy of extended-shelf-life ⁹⁰Y glass microspheres in a larger, 134-patient cohort. The increase in number of microspheres administered theoretically resulted in better tumor distribution of the microspheres without an increase in adverse events.