PI-103 is the use of targeting the visible contrast enhancing lesion

urgical boost to the contrast enhancing postoperative surgical bed. Although this trial failed to demonstrate a survival advantage by boosting the contrast enhancing surgical bed, an American Society for Radiation Oncology review statement regarding the use of SRS in the treatment of malignant gliomas stated, optimal SRS boost therapy PI-103 remains to be elucidated. One possible flaw with SRS boost techniques is the use of targeting the visible contrast enhancing lesion. Magnetic resonance spectroscopy studies have documented areas of increased metabolic activity outside the region of contrast enhancement. This leaves the possibility that better SRS boost techniques and better patient selection may improve survival as compared with conventionally treated patients who are treated without a SRS boost.
Efforts have been directed toward accurately defining high risk regions of high grade gliomas that appear more aggressive and may benefit from additional targeted limited volume SRS without the increased risk of large volume treatment toxicity. Magnetic resonance spectroscopy, positron emission tomography imaging using radiolabeled glucose as well as methionine, and MR tumor perfusion imaging are noninvasive functional imaging techniques that are being used in addition to conventional MR imaging to help identify high risk regions in large gliomas. Of these techniques, MRS has the broadest availability and reported experience. It has been shown that in MR spectra, active gliomas exhibit a high resonance in the choline spectral peak and a low NAA or creatine resonance correlating with high choline/NAA or choline/creatine ratios for active tumors vs.
low ratios for areas of inactivity. In an analysis of 36 patients with recurrent high grade gliomas treated with SRS, patients with MR spectroscopic high risk regions that were within the SRS target had an improved survival and increase in time to further treatment compared with those patients with MRspectroscopic high risk regions outside the SRS target. In a study of 31 patients with high grade gliomas resected after conventional MRI and MRS, MRS was found to more accurately define the tumor boundary than conventional MR using histopathologic correlation. On pretreatment analysis of 34 patients with highgrade gliomas, high risk regions by MRS were found to be significantly smaller than in conventional T2 imaging, suggesting an ability to decrease the amount of normal brain tissue within the MRS determined target, thus potentially limiting side effects.
The purpose of this prospective Phase II study was to determine the feasibility and efficacy of a stereotactic radiosurgical boost directed at high risk tumor regions as determined byMRScombined with standard conformal radiotherapy for patients with GBM. Methods and Materials Patient selection Between December 2002 and September 2007, 35 patients with newly diagnosed GBM were enrolled in this prospective Phase II trial, which was registered with www.clinicaltrials.gov and was approved by the University Hospitals of Cleveland institutional review board. All patients signed detailed informed consent forms approved by the institutional review board. The protocol was annually reviewed by the University Hospitals of Cleveland data safety monitoring committee. All

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