CLINICAL-PATIENT STUDIES Time course of imaging changes of GBM during extended bevacizumab treatment Suchitra Ananthnarayan Æ Jennie Bahng Æ James Roring Æ Phioanh Nghiemphu Æ Albert Lai Æ Timothy Cloughesy Æ Whitney B. Pope Received: 10 September 2007 / Accepted: 26 March 2008 Ó Springer Science+Business Media, LLC. 2008 Abstract Glioblastoma multiforme (GBM) are morpho- logically heterogeneous tumors, with varying amounts of necrosis, and edema. Previous studies have shown that treatments incorporating the VEGF antibody bevacizumab can reduce edema and tumor burden in GBM. Additionally it has been suggested that bevacizumab regimen treatment reduces the percent of tumoral necrosis. Therefore we sought to (1) determine the time course of change in necrosis, tumor, and edema volume in patients who respond to bevacizumab regimen treatment and (2) deter- mine if GBM that progress following a response to bevacizumab regimen treatment are morphologically dif- ferent from their appearance at prior tumor progression. Therefore, we retrospectively assessed tumor, necrosis, and edema volumes on MRI scans from 15 patients with recurrent GBM who responded to bevacizumab regimen treatment, and had extended ( [ 7 month) follow-up. We found that the median time to best tumor response was 158 days (range, 16–261, SD = 63). The median best response was 72.1% reduction in tumor volume and 72.8% reduction in peritumoral edema. Most tumors (77.8%) showed resolution of necrotic areas. The relative reduction of edema and necrosis was sustained, even in patients (n = 7) who developed tumor progression. Thus the mean ratio of edema-to-tumor volume at progression on bev- acizumab regimen treatment was 38.4% lower than that for the same tumors seen on progression scans following prior chemotherapy. The percentage of necrotic tumor also was diminished following progression on bevacizumab regimen treatment. These findings illustrate the time course of changes in edema and tumor volume with prolonged bev- acizumab regimen treatment, and support the conclusion that the morphology of recurrent GBM following bev- acizumab regimen therapy is distinct from that on other chemotherapy. Keywords Bevacizumab Á GBM Á Glioma Á VEGF Á Tumor Á Edema Á Necrosis Á Volume analysis Abbreviations GBM Glioblastoma multiforme VEGF Vascular endothelial growth factor MRI Magnetic resonance imaging TTR Time to partial tumor response TTP Time to tumor progression RT Radiation therapy RECIST Response evaluation criteria in solid tumors Introduction Glioblastoma multiforme (GBM) are the most aggressive and infiltrative of primary brain tumors. Heterogeneous in appearance and gene expression, GBM share a poor prog- nosis [1]. VEGF and its receptors are more highly expressed in GBM than in other brain tumors [2]. VEGF is a potent mediator of cerebrovascular permeability and is thought to play a significant role in tumor progression through regula- tion of endothelial cell permeability, activation, survival, proliferation, invasion, and migration [3]. Cerebrovascular S. Ananthnarayan Á J. Bahng Á J. Roring Á W. B. Pope (&) Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Ave., BL-428, CHS, Los Angeles, CA 90095-1721, USA e-mail: wpope@mednet.ucla.edu P. Nghiemphu Á A. Lai Á T. Cloughesy Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA 123 J Neurooncol DOI 10.1007/s11060-008-9573-x