Glioblastoma: A Method for Predicting Response to Antiangiogenic Chemotherapy by Using MR Perfusion Imaging—Pilot Study

Abstract

Purpose:To derive a magnetic resonance (MR)-based imaging metric that refl ects local perfusion changes resulting from the administration of angiogenic-inhibiting chemotherapy in patients with recurrent glioblastoma multiforme (GBM). Materials and Methods:In this retrospective Institutional Review Board-approved HIPAA-compliant study, 16 patients (12 men, four women; mean age, 51.8 years 6 15.1 [standard deviation]) with recurrent GBM received bevacizumab every 3 weeks (15 mg per kilogram of body weight) as part of a clinical trial. Baseline MR images were acquired, and follow-up images were acquired every 6 weeks thereafter until tumor progression or death. Imaging included perfusion and T1-weighted contrast material-enhanced MR imaging. Perfusion images were analyzed both with and without correction for contrast material leakage. The volumes of interest were selected as enhancing voxels on T1-weighted contrast-enhanced MR images. Relative cerebral blood volume (rCBV) maps were created from analysis of MR perfusion images. The volumes of interest were used to calculate the following parameters: size, mean rCBV, mean leakage coeffi cient K 2 , and hyperperfusion volume (HPV), which is the fraction of the tumor with an rCBV higher than a predetermined threshold. Percent change in each parameter from baseline to fi rst follow-up was compared with time to progression (TTP) by using a Cox proportional hazards model with calculation of hazard ratios. Results:The most signifi cant hazard ratio was seen with a D HPV cutoff of rCBV greater than 1.00 (hazard ratio, 1.077; 95% confi dence interval: 1.026, 1.130; P = .002). The only significant ratios greater than one were those that resulted from perfusion calculated as mean rCBV and D HPV. The ratios were also higher after correction for leakage. Conclusion:This pilot study derived an imaging metric (HPV) that refl ects local perfusion changes in GBMs. This metric was found to show a signifi cantly improved correlation to TTP as compared with more commonly used metrics.q RSNA, 2010 1

Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?

“…Four studies of recurrent HGGs have reported early pharmacodynamic reductions in K trans following bevacizumab with or without cytotoxic therapy between 4 days and 6 weeks after initiation of therapy, akin to mRCC and HCC data. However, unlike the results from mRCC and HCC studies, reductions in K trans did not show significant relationships with PFS or OS in HGG (44,45,47,48). These data differ from a similar sized study of 28 glioblastoma multiforme patients with recurrence treated with cediranib, where early reduction in K trans was significantly related to OS (49).…”

“…This parameter has also distinguished progressors from nonprogressors in patients receiving bevacizumab and cytotoxic therapy (56). Similarly, studies report that the amount of tumor with high BV (48) or low/skewed apparent diffusion coefficient (ADC) values (57)(58)(59) show a relationship to tumor PFS and OS that is obscured when average values of BV and ADC are used. However, these approaches rely on a priori assumptions to define the subregion of interest, and further work is required to define objective, data-driven tumor regions (60,61) that relate to response, relapse, and clinical outcome.…”

O-(2-18F-Fluoroethyl)-L-Tyrosine PET Predicts Failure of Antiangiogenic Treatment in Patients with Recurrent High-Grade Glioma

“…The estimated relative cerebral blood volume measured by perfusion MRI is a semiquantitative parameter that correlates with the number of capillaries (22) and glioma grading (23). MRI perfusion showed correlations with PFS during antiangiogenic treatment (24) and can differentiate between recurrent tumor and pseudoprogression (25). Chen et al (18) evaluated antiangiogenic treatment response using 39-deoxy-39-18 F-fluorothymidine.…”

Cerebrovascular Occlusive Disease: Quantitative Cerebral Blood Flow Using Dynamic Susceptibility Contrast MR Imaging Correlates with Quantitative H2[15O] PET

“…This quantitation process was performed automatically and without manual intervention by using in-house software written in Matlab (Matlab 2009a; Mathworks, Natick, Mass), based on the bookend method outlined above and previously applied in clinical studies of cancer (18,19), multiple sclerosis (20), and acute stroke (21). In large clinical studies this automated perfusion quantitation technique has been found to be robust, repeatable, and reliable (15).…”