Survival prediction based on qualitative MRI diffusion signature in patients with recurrent high grade glioma treated with bevacizumab

Abstract

Background: Bevacizumab was approved by the FDA for the treatment of recurrent or progressive glioblastoma (GBM). Imaging responses are typically assessed by gadolinium-enhanced MRI. We sought to determine the significance of qualitative diffusion signature (manifest as variable degree of dark signal) on ADC maps in recurrent gliomas after treatment with bevacizumab.

Methods: We performed an institutional review board (IRB) approved retrospective study on patients who underwent MRI of the brain after 8 weeks of receiving bevacizumab for recurrent glioma. Patients were divided into three groups based on qualitative diffusion signature: (I) lesion not bright on diffusion weighted imaging (DWI) suggestive of no restricted diffusion (FDR₀); (II) lesion bright on DWI with corresponding homogenous dark signal on apparent diffusion coefficient (ADC) maps suggestive of focal restricted diffusion likely due to bevacizumab induced necrosis (FDR_n); and (III) lesion bright on DWI with corresponding homogenous faint dark signal on ADC maps suggestive of focal restricted diffusion likely due to viable tumor or heterogeneous spectrum of dark and faint dark signals on ADC maps suggestive of focal restricted diffusion likely due to viable tumor surrounding the bevacizumab induced necrosis (FDR_t).

Results: Based on the qualitative signal on diffusion weighted sequences after bevacizumab therapy, total number of patients in group (I) were 14 (36%), in group (II) were 17 (44%); and in group (III) were 8 (20%). The median overall survival (OS) from the time of recurrence in patients belonging to group (II) was 364 days vs. 183 days for those with group (I) vs. 298 days for group (III). On simultaneous comparison of survival differences in all three groups by Kaplan-Meier analysis, group (II) was significant in predicting survival with P values for the log-rank tests <0.033.

Conclusions: In patients with recurrent glioma treated with bevacizumab, the presence of homogenous dark signal (FDR_n) on ADC maps at 8 weeks follow-up MRI correlated with a longer survival. Thus, use of this qualitative diffusion signature in adjunct to contrast enhanced MRI may have the widest potential impact on routine clinical care for patients with recurrent high-grade gliomas. However, prospective studies analysing its predictive value are warranted.

Keywords: Recurrent glioblastoma multiforme (GBM); apparent diffusion coefficient (ADC); bevacizumab; diffusion weighted imaging (DWI); median survival.

Figure 1

Development of acute infarct phenotype diffusion restriction in a 57-year-old male with recurrent GBM following 2 months of bevacizumab. Pre-treatment Post Gad T1WI demonstrating peripheral enhancement surrounding the surgical cavity in the left posterior temporal lobe suggestive of recurrent GBM (A). After 2 months of treatment (B-E). Post Gad T1WI demonstrating shrinkage of cavity and slightly decreased surrounding enhancement compared to pre-treatment with more focal enhancement posterolaterally (B), non-enhancing high FLAIR signal adjacent to residual cavities (C) and small area of high signal on DWI (D) adjacent to temporal horn of left ventricle with corresponding dark signal on ADC (E) akin to acute infarct phenotype (red circles) suggestive of focal diffusion restriction due to necrosis (FDR_n). Post Gad T1WI after 6 months of bevacizumab (F) demonstrating no progression/increased enhancement in the area of FDRn noted at 2 months (yellow arrow). GBM, glioblastoma.

Figure 2

Development of subacute infarct phenotype diffusion restriction in a 54-year-old male with recurrent GBM following 2 months of bevacizumab. Pre-treatment (A,B), non-enhancing high FLAIR signal adjacent to the surgical cavity in the right parietal lobe (A) and peripheral enhancement adjacent to posterior margin of surgical cavity on post Gad T1WI (B), suggestive of recurrent GBM. After 2 months of treatment (C-F), decreased non-enhancing high FLAIR signal adjacent to the surgical cavity (C) and resolution of previously seen surrounding enhancement however there is new fain enhancement along the posterior margin of surgical cavity on Post Gad T1WI (D), and small area of high signal on DWI (E) adjacent to posterior margin of cavity with corresponding faint dark signal on ADC (F) akin to subacute infarct phenotype (red circles) suggestive of focal diffusion restriction due to viable tumor (FDR_t). Post Gad T1WI after 6 months of bevacizumab (G-H) demonstrating progression: increased enhancement (G) and increased non-enhancing high FLAIR signal (H) in the area of FDRt noted at 2 months (yellow arrow). GBM, glioblastoma; DWI, diffusion weighted imaging; ADC, apparent diffusion coefficient.

Figure 3

Diffusion signature demonstrating FDR_n and FDR_t.

Figure 4

Kaplan-Meier survival curve demonstrating median overall survival in days from time of recurrence.