patients underwent either biopsy or surgical resection to confirm the diagnosis of GBM and were reviewed at a multidisciplinary neuro oncology tumor board with confirmation by STF-62247 STF62247 a neuropathologist at University Hospitals. Inclusion and exclusion criteria are listed in Table 1. MRS and pretreatment MRS image processing All patients underwent postoperative MRS with a 10 10 15 mm voxel size. The entire area of T2 abnormality on each postoperative scan was analyzed. Choline, NAA, and creatinespectrographic peaks were identified, with choline and NAA normalized to baseline creatine levels. If creatine levels were 0, no data were identified for that voxel. Those voxels with a normalized choline/NAA ratio in excess of 2 were manually identified and marked.
Those marked voxels were highlighted on the T2 sequence, and another DICOM image set with the highlighted voxels was created using the image fusion and voxel paint routines on MIM Vista Software versions 3.0 to 3.5. The MARKED MRS DICOM image set was then transferred to the Gamma Knife treatment planning console. Gamma Knife SRS All patients underwent Gamma Knife SRS within 5 weeks of surgery, with use of either a Model B or 4C Leksell Gamma Knife unit with 60Co sources. During treatment planning the MARKED MRS scan was fused with the Gamma Knife planning frame based scan using the fusion function within the Gamma Plan Gamma Knife planning software. The highlighted voxels on the MARKED MRS scan within 2 cm of the contrast enhancing lesion on the Gamma Knife planning scan were targeted with a single 8 mm isocenter to the 50% isodose curve.
The combined isocenters from all treated highlighted voxels created the final treatment plan. The volume of the dose matrix within the 50% isodose curve was measured. An equivalent sphere diameter of that volume was created using 4/3p3. On the basis of the RTOG 90 05 criteria, the prescription dose was 15 Gy for diameters 3e4 cm, 18 Gy for diameters 2e2.9 cm, and 24 Gy for diameters 2 cm. If the diameter was calculated to be 4 cm, the patient was not a candidate for the trial and was offered off protocol treatment. All patients received a loading dose of an anticonvulsant 1 day before SRS and intravenous dexamethasone on the day of SRS. Stereotactic radiosurgery was performed before conformal radiotherapy to minimize impact of postradiation changes on the MRS analysis.
Conformal radiotherapy All patients underwent three dimensional conformal radiotherapy within 2 weeks of completing SRS. Intensity modulated radiotherapy was not allowed, to achieve uniformity in the treatment plans and to minimize low dose spill beyond the planning target volumes. One treatment of 2.0 Gy was given daily 5 days per week for a total of 60.0 Gy. All portals were treated during each treatment session. Each patient was treated in the supine position, with a thermoplastic mask used for reproducibility. All patients underwent postoperative MRI within 2 days of surgery. For the first 46 Gy in 23 fractions, the treatment volume included the volume of contrast enhancing lesion and surrounding edema on postoperative MRI scan plus a 2 cm margin. If no surrounding edema was present, the initial target volume included the T1 contrast enhancing lesion plus a 2.5 cm margin. After 46 Gy, the boos