A Microdosimetric Analysis of Absorbed Dose to Tumor as a Function of Number of Microspheres per Unit Volume in 90Y Radioembolization

Differences in maximum tolerable absorbed dose to normal liver between ⁹⁰Y radioembolization and external-beam radiation therapy have been explained by citing differences in absorbed-dose heterogeneity at the microscopic level. We investigated microscopic absorbed-dose heterogeneity in radioembolization as a function of the number of microspheres per unit volume in tumor. The goal was to determine what effect the number of microspheres may have, if any, on tumor control in ⁹⁰Y radioembolization. Methods: ⁹⁰Y PET/CT data were combined with microscopic probability-density functions describing microsphere clustering to provide realistic simulation using Monte Carlo modeling on both a macroscopic and a microscopic level. A complete microdosimetric analysis using 100-μm voxels was performed on the basis of ⁹⁰Y PET/CT data from 19 tumors treated using radioembolization. Simulations were performed with average tumor microsphere-number densities from 200 to 70,000 spheres/mL. Monte Carlo simulations of each tumor and number density were repeated 20 times to establish SE. A 2-way balanced ANOVA was used to determine whether differences in microsphere-number density affected common tumor-dose metrics. Results: Decreasing the microsphere-number density resulted in a decrease in D₇₀, the minimum dose to 70% of the tumor. The slope of the dose–volume histogram also decreased with decreasing microsphere-number density in all tumors. Compared with a density of 50,000 spheres/mL, decreases in D₇₀ were statistically significant below 20,000 spheres/mL. However, these differences are unlikely to have clinical significance until the density decreases to below 5,000 spheres/mL. Although D₇₀ was decreased at a low microsphere-number density, one can compensate for decreases by an increase in the average tumor-absorbed dose, that is, by increasing the radioembolization treatment dose. Conclusion: Differences in microsphere-number density may have an effect on microscopic tumor absorbed-dose inhomogeneity. These results begin to explain differences in treatment planning strategies between glass and resin radioembolization devices.

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