Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients

Abstract

The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.

Restriction spectrum imaging predicts response to bevacizumab in patients with high-grade glioma

“…Similarly, researchers have shown that the volume of the low ADC within the FLAIR/T2 region gradually increases following treatment with anti-angiogenic agents in a sizable subset of patients. 22,27 These findings add to existing evidence that while bevacizumab may control disease in the CE region, it leads to nonenhancing, infiltrative tumor growth that likely contributes to unfavorable patient outcomes. This hypothesis is strengthened by preclinical studies in mouse glioma models that suggest that blocking VEGF leads to a more infiltrative pattern of tumor growth.…”

“…17 More recently, traditional and graded functional diffusion maps (fDMs) have been employed that characterize different thresholds of ADC change on a voxelwise basis in order to estimate cellularity changes occurring in subportions of the tumor. 18 -21 Collectively, these methods demonstrate initial promise in the prediction and evaluation of response to bevacizumab; however, results have occasionally been conflicting, with some studies reporting that a lower ADC is associated with shorter PFS and OS 10,15,16,22 and others reporting that a higher ADC is associated with shorter PFS and OS. 20,23 Although the reason for opposing findings is not entirely clear, a more direct marker of tumor cellularity within the voxel itself (eg, restricted diffusion within cells) that is not influenced by edema and other pathologies in the extracellular matrix would greatly simplify the interpretation of DWI changes and could improve the evaluation of treatment response.…”

Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in Patients with Recurrent Glioblastoma

“…In addition, there have been five patients from literature with sampled biopsies and two brain donations demonstrating necrosis within these focal regions 21,26,28,37,38 . Zhang et al however found that survival was dependent on the size of the focal lesion 23 .…”

“…Next, we assess a patient population to determine the effect these lesions have on OS. We then perform a sub-analysis on tumor O 6 -methylguanine-DNA-methyltransferase (MGMT) methylation, a predictor of overall survival 23,32 .…”

Diagnostic Accuracy of T1-Weighted Dynamic Contrast-Enhanced–MRI and DWI-ADC for Differentiation of Glioblastoma and Primary CNS Lymphoma

“…In order to reduce variability related to scanner heterogeneity, contrast, and patient physiology (e.g., cardiac output), all parameters were normalized to normal brain by placing ROIs (standardized area of 40–60 mm 2 ) in normal appearing white matter of the contralateral hemisphere at the mid-level of the tumor. 21–23 The ROI was placed on the contrast-enhanced T1-weighted images, and then transferred to the VP and Ktrans maps and adjusted if necessary to avoid potential outlier areas that may harbor subtle microvascular leakage. The ADC, Vp, and Ktrans measurements were binned and histogram analysis was performed to determine the mean and 90th percentile normalized values for Vp (rVp mean ; rVp 90%tile ) and Ktrans (rKtrans mean ; rKtrans 90%tile ), and the mean and 5th percentile normalized values for ADC (rADC mean ; rADC 5%tile ).…”