title: Demonstration of DCE-MRI as an early pharmacodynamic biomarker of response to VEGF Trap in glioblastoma.
abstract: Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered. Regions of interest on each image slice were combined to produce a volume of interest representative of the entire tumor. Percent and absolute changes in maximum FDG-avidity, mean apparent diffusion coefficient (ADC), Ktrans, and Ve were calculated per lesion. Among the 12 participants that underwent dynamic contrast enhanced MRI (DCE-MRI), there were large, statistically significant reductions in Ktransand Ve (median difference = -41.8 %, p < 0.02 and -42.6 %, p < 0.04, respectively). In contrast, there were no significant reductions in ADC or FDG-PET SUVmax values. DCE-MRI is a useful measure of early pharmacodynamic effects of VEGF Trap on tumor vasculature. The absence of significant changes in FDG-PET and DW-MRI suggest that the early pharmacodynamic effects are specific to tumor perfusion and/or permeability and do not directly inhibit metabolism or induce cell death. DCE-MRI in conjunction with standard imaging may be promising for the identification of anti-angiogenic effects in this patient population with this therapeutic target. Further studies are needed to evaluate the relationship between DCE-MRI response and clinical outcome.
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02215, USA. allison_oneill@dfci.harvard.edu.
authors: Allison F
authors: AF
authors: O'Neill
authors: Department of Imaging and Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.|Department of Radiology, Brigham and Women's Hospital, Boston, MA, 02115, USA.|Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, 02215, USA.
authors: Lei
authors: L
authors: Qin
authors: Center for Neuro-oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
authors: Patrick Y
authors: PY
authors: Wen
authors: The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors: John F
authors: JF
authors: de Groot
authors: Department of Imaging and Center for Biomedical Imaging in Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.|Department of Radiology, Brigham and Women's Hospital, Boston, MA, 02115, USA.|Tumor Imaging Metrics Core, Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, 02215, USA.
authors: Annick D
authors: AD
authors: Van den Abbeele
authors: Department of Radiology, Center for Quantitative Cancer Imaging, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
authors: Jeffrey T
authors: JT
authors: Yap
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; DCE-MRI; Glioblastoma; VEGF