title: A Microdosimetric Analysis of Absorbed Dose to Tumor as a Function of Number of Microspheres per Unit Volume in 90Y Radioembolization.
abstract: Differences in maximum tolerable absorbed dose to normal liver between (90)Y 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 (90)Y radioembolization.
  
  
  
  (90)Y 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 (90)Y 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Radiology, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland; and alexander.pasciak@gmail.com.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Pasciak
authors.affiliation: Department of Radiology, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee Department of Radiology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Austin C
authors.initials: AC
authors.lastname: Bourgeois
authors.affiliation: Department of Radiology, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.
authors.forename: Yong C
authors.initials: YC
authors.lastname: Bradley
mesh_terms: D000465:Algorithms; D004307:Dose-Response Relationship, Radiation; D004621:Embolization, Therapeutic / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D008863:Microspheres; D009010:Monte Carlo Method; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes
keywords: 90Y; interventional oncology; radioembolization; yttrium-90