title: Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib.
abstract: To evaluate the role of apparent diffusion coefficient (ADC) imaging in assessing tumor cell infiltration after treatment with the antivascular endothelial growth factor (anti-VEGF) agent, cediranib, we prospectively analyzed diffusion MRI scans from 30 patients participating in a Phase II trial of cediranib for recurrent glioblastoma. A patient-specific threshold was selected below which ADC values were determined to be abnormally low and suggestive of tumor. We determined the percent of low ADC in the FLAIR hyperintensity surrounding the enhancing tumor and then visualized the location of these low ADC voxels. The percent volume of the FLAIR hyperintensity comprised by low ADC increased significantly from baseline (2.3%) to day 28 (2.9%), day 56 (5.0%), and day 112 (6.3%) of treatment with cediranib suggesting increasing infiltrative tumor in some patients. Visualization of the location of the low ADC voxels suggested regions of tumor growth that were not visible on contrast-enhanced MRI. ADC maps can be used to suggest regions of infiltrative tumor cells with anti-VEGF therapy and should be validated in future studies.
authors.affiliation: Departments of Neurology, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. egerstner@partners.org
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Gerstner
authors.forename: Poe-Jou
authors.initials: PJ
authors.lastname: Chen
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.forename: Gregory
authors.initials: G
authors.lastname: Sorensen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D018572:Disease-Free Survival; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use*; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
references.citation: J Clin Oncol. 2008 Jul 10;26(20):3387-94
references.pmid: 18541899
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16759-64
references.pmid: 16267128
references.citation: Cancer Res. 2001 Jul 1;61(13):4971-3
references.pmid: 11431326
references.citation: Radiol Clin North Am. 1988 Jul;26(4):873-87
references.pmid: 3289078
references.citation: Clin Cancer Res. 2008 Jun 15;14(12):3832-9
references.pmid: 18559603
references.citation: Neuro Oncol. 2008 Dec;10(6):940-5
references.pmid: 18708344
references.citation: J Natl Cancer Inst. 2000 Dec 20;92(24):2029-36
references.pmid: 11121466
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5524-9
references.pmid: 15805192
references.citation: Nat Rev Neurosci. 2007 Aug;8(8):610-22
references.pmid: 17643088
references.citation: Clin Cancer Res. 1997 Sep;3(9):1457-66
references.pmid: 9815831
references.citation: Neurology. 2008 Mar 4;70(10):779-87
references.pmid: 18316689
references.citation: Neuroimaging Clin N Am. 2006 Nov;16(4):619-32, viii-ix
references.pmid: 17148023
references.citation: Nat Clin Pract Oncol. 2008 Nov;5(11):634-44
references.pmid: 18711427
references.citation: Cancer Res. 2006 May 1;66(9):4687-92
references.pmid: 16651420
references.citation: Neoplasia. 2000 Jul-Aug;2(4):306-14
references.pmid: 11005565
references.citation: Cancer Cell. 2007 Jan;11(1):83-95
references.pmid: 17222792
references.citation: J Clin Oncol. 1990 Jul;8(7):1277-80
references.pmid: 2358840
references.citation: Radiology. 2005 Mar;234(3):756-64
references.pmid: 15734932
references.citation: Cancer Res. 2001 Sep 15;61(18):6624-8
references.pmid: 11559524
references.citation: Clin Cancer Res. 2004 Dec 1;10(23):7852-9
references.pmid: 15585617
references.citation: J Clin Oncol. 2003 Mar 15;21(6):1094-100
references.pmid: 12637476
references.citation: Clin Cancer Res. 2007 May 15;13(10):2897-904
references.pmid: 17504989
references.citation: J Clin Oncol. 2001 Jan 15;19(2):551-7
references.pmid: 11208850