title: Microvesicles as a Biomarker for Tumor Progression versus Treatment Effect in Radiation/Temozolomide-Treated Glioblastoma Patients.
abstract: The standard of care for glioblastoma (GB) is surgery followed by concurrent radiation therapy (RT) and temozolomide (TMZ) and then adjuvant TMZ. This regime is associated with increased survival but also increased occurrence of equivocal imaging findings, e.g., tumor progression (TP) versus treatment effect (TE), which is also referred to as pseudoprogression (PsP). Equivocal findings make decisions regarding further treatment difficult and often delayed. Because none of the current imaging assays have proven sensitive and specific for differentiation of TP versus TE/PsP, we investigated whether blood-derived microvesicles (MVs) would be a relevant assay.
  
  
  METHODS
  2.8 ml of citrated blood was collected from patients with GB at the time of their RT simulation, at the end of chemoradiation therapy (CRT), and multiple times following treatment. MVs were collected following multiple centrifugations (300g, 2500g, and 15,000g). The pellet from the final spin was analyzed using flow cytometry. A diameter of approximately 300 nm or greater and Pacific Blue-labeled Annexin V positivity were used to identify the MVs reported herein.
  
  
  RESULTS
  We analyzed 19 blood samples from 11 patients with GB. MV counts in the patients with stable disease or TE/PsP were significantly lower than patients who developed TP (P = .014).
  
  
  CONCLUSIONS
  These preliminary data suggest that blood analysis for MVs from GB patients receiving CRT may be useful to distinguish TE/PsP from TP. MVs may add clarity to standard imaging for decision making in patients with equivocal imaging findings.
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Koch
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lustig
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Walter T
authors.initials: WT
authors.lastname: Jenkins
authors.affiliation: Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolf
authors.affiliation: Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez-Lage
authors.affiliation: Department of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Arati
authors.initials: A
authors.lastname: Desai
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Dewight
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: sydevans@mail.med.upenn.edu.
authors.forename: Sydney M
authors.initials: SM
authors.lastname: Evans