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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.

SUBMITTER: Gerstner ER

PROVIDER: S-EPMC2940624 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib.

Gerstner Elizabeth R ER Chen Poe-Jou PJ Wen Patrick Y PY Jain Rakesh K RK Batchelor Tracy T TT Sorensen Gregory G

Neuro-oncology 20100122 5

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 AD ...[more]

PMID: 20406897

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Project description:Cediranib is a small-molecule pan-vascular endothelial growth factor receptor inhibitor. The tumor response to short-term cediranib treatment was studied using dynamic contrast-enhanced and diffusion-weighted MRI at 7 T, as well as (18) F-fluoromisonidazole positron emission tomography and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline; they then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow-up imaging performed 2 h after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, the endothelial cell marker CD31, smooth muscle actin, intercapillary distance and tumor necrosis. Dynamic contrast-enhanced MRI-derived parameters decreased significantly in cediranib-treated tumors relative to pretreatment values [the muscle-normalized initial area under the gadolinium concentration curve decreased by 48% (p=0.002), the enhancing fraction by 43% (p=0.003) and K(trans) by 57% (p=0.003)], but remained unchanged in controls. No change between the pre- and post-treatment tumor apparent diffusion coefficients in either the cediranib- or vehicle-treated group was observed over the course of this study. The (18) F-fluoromisonidazole mean standardized uptake value decreased by 33% (p=0.008) in the cediranib group, but showed no significant change in the control group. Histological analysis showed that the number of CD31-positive vessels (59 per mm(2) ), the fraction of smooth muscle actin-positive vessels (80-87%) and the intercapillary distance (0.17 mm) were similar in cediranib- and vehicle-treated groups. The fraction of perfused blood vessels in cediranib-treated tumors (81 ± 7%) was lower than that in vehicle controls (91 ± 3%, p=0.02). The necrotic fraction was slightly higher in cediranib-treated rats (34 ± 12%) than in controls (26 ± 10%, p=0.23). These findings suggest that short-term treatment with cediranib causes a decrease in tumor perfusion/permeability across the tumor cross-section, but changes in vascular morphology, vessel density or tumor cellularity are not manifested at this early time point.

Dataset Information

Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib.

Publications

Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib.

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