Abstract
The standard of care for glioblastoma (GB) is radiation therapy (RT) and temozolomide (TMZ) following optimal surgery. This regimen has been accompanied by an increase in the occurrence of equivocal imaging findings, e.g. tumor progression vs. treatment effect (TE), which includes pseudoprogression (PsP). Thus decisions regarding further treatment are difficult and often delayed. None of the current imaging methods for identifying TE/PsP have proven sensitive and specific. Therefore, we developed a method to isolate microvesicles (MV) from blood sample in patients with GB. MV are defined herein as lipid membrane-bound sacs with a diameter >300 nm. METHODS: 3 ml citrated blood was collected from GB patients at their RT simulation and at multiple times during and following treatment. MV were isolated during multiple centrifugations (300g, 2500g, 15,000g). The pellet from the final spin was analyzed using flow cytometry. Antibodies to phosphotidylserine were used to identify the MV. RESULTS: We analyzed 16 blood samples from 10 GB patients that met analysis criteria: the MV sample was obtained at or following the completion of CRT and, a definitive diagnosis (TP, TE or PSP) was reached within 60 days of the date of the sample. MV counts in the patients with stable disease or TE/PsP were significantly lower than patients who developed recurrence or died of their disease (p = 0.0385). Based on MRI and/or pathological assessment, 2 patients have died of their disease, 1 patient is alive with recurrence, 3 patients have stable disease and 4 patients are being followed for PsP vs. tumor progression (TP). SUMMARY/CONCLUSION: These preliminary data suggest that the analysis of blood (liquid biopsy) for MV may be useful to distinguish TE/PsP from TP in GB patients. MVs may be valuable in addition to standard imaging for decision making in patients with equivocal imaging findings.
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