In-vitro Biological Dosimeter Modeling Glioblastoma Radioresponse To Gamma Knife

Keywords: gamma knife, dosimetry, glioblastoma multiforme, animal model, brain tumor

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     To develop an assay for the assessment of glioma cell response to single fraction high dose Gamma Knife™ radiosurgery, which allows for the isolation of radioresistant cell subpopulations, thus facilitating mechanistic studies of radioresistance. Further, to more accurately model in vitro, the biological environment in which gliomas are treated in vivo.
     A tissue equivalent paraffin phantom with a cassette aperture capable of holding an OpticellTM cell culture cassette was developed for treatment with the Gamma Knife™ model C. A second adapter was developed for the Perfexion phantom. GBM cells were cultured and plated in OpticellTM cassettes. The cells were treated with single fraction radiosurgery to the center of the cassette at 24Gy maximum with an 18mm collimator (16mm in Perfexion). After treatment, the cells were morphologically assessed for response to radiosurgery. Two specific parameters were used to determine radiosensitivity; 1) the diameter of the clearing zone, defined as the central region of cell death, and 2), the number of surviving colonies within this central high dose clearing zone.
     The radioresistance of 2 cell lines (ME and DIV) from glioblastomas multiforme (GBMs) were compared. ME was established from a primary tumor (prior to treatment) and DIV was established from a tumor that recurred following chemotherapy and fractionated radiotherapy. ME had a more robust response to radiosurgery as characterized by a consistently larger clearing zone (28.33 +/- 1.1mm) in comparison to the cell line DIV, which produced a clearing zone of 24.0 +/- 1 mm, indicating an approximate response difference of 5 Gy. The mean number of surviving colonies within the clearing zone for ME was 1.33 +/-1, compared with 66.67 +/- 2 for DIV.
     This is a retrospective study.
       We developed a new biologic dosimeter to model the response of cells from GBM to single fraction radiosurgery. Statistically significant differences between primary and recurrent tumor cell lines were documented.
     This system allows for the identification and isolation of radioresistant cells. It also allows for glioma cells to be treated in an environment where adjacent cells are exposed to a marginal dose, thus more accurately modeling the populations of cells surrounding tumors in vivo.


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