BACKGROUND: (blind field). METHODS: We evaluated MRI markers in 84 GBM patients enrolled in phase 2 trials (NCT00305656, NCT00662506) to investigate the mechanisms of tumor response to anti-VEGF treatment. Forty newly diagnosed GBM (nGBM) patients were treated with the oral pan-VEGFR inhibitor, cediranib, in combination with radiation and temozolomide. Fourteen nGBM patients were treated with radiation and temozolomide alone. Thirty recurrent GBM (rGBM) patients were treated with cediranib alone. All patients underwent serial brain MRI scans at uniform time points. RESULTS: In both the nGBM and rGBM cohorts treated with cediranib, increased tumor perfusion was observed in 20/40 and 7/30 patients, respectively. In contrast, in the nGBM cohort not treated with cediranib increased tumor perfusion was observed in 1/14 patients. Increased tumor perfusion was associated with improved overall survival in nGBM (p = 0.040) and rGBM (p = 0.009) patients. Moreover, increased perfusion was associated with improved tumor oxygenation status in patients the nGBM patients treated with cediranib and chemoradiation. These findings are consistent with a recent report in rGBM patients treated with bevacizumab. CONCLUSIONS: Anti-VEGF therapy confers clinical benefit to GBM patients by normalization of tumor vessels. We hypothesize that the subset of GBM subjects who experience increased perfusion and improved tumor oxygenation status after anti-VEGF therapy will derive optimal benefit from concurrent chemoradiation and innate anti-tumor immune mechanisms. MRI techniques may enable early identification of GBM patients most likely to benefit from this expensive, and potentially toxic, class of anti-cancer drugs. SECONDARY CATEGORY: Imaging.