Regorafenib in Glioblastoma Recurrence: How to Deal With MR Imaging Treatments Changes

Abstract

The treatment of recurrent high-grade gliomas remains a major challenge of daily neuro-oncology practice, and imaging findings of new therapies may be challenging. Regorafenib is a multi-kinase inhibitor that has recently been introduced into clinical practice to treat recurrent glioblastoma, bringing with it a novel panel of MRI imaging findings. On the basis of the few data in the literature and on our personal experience, we have identified the main MRI changes during regorafenib therapy, and then, we defined two different patterns, trying to create a simple summary line of the main changes of pathological tissue during therapy. We named these patterns, respectively, pattern A (less frequent, similar to classical progression disease) and pattern B (more frequent, with decreased diffusivity and decrease contrast-enhancement). We have also reported MR changes concerning signal intensity on T1-weighted and T2-weighted images, SWI, and perfusion imaging, derived from the literature (small series or case reports) and from our clinical experience. The clinical implication of these imaging modifications remains to be defined, taking into account that we are still at the dawn in the evaluation of such imaging modifications.

Keywords: MRI; glioblastoma; imaging; regorafenib; treatment changes.

Figure 1

Pattern A. MRI changes in recurrent high grade glioma under regorafenib, pattern A. MRI scans performed at baseline (top image) and 3 months after first administration of REG therapy (bottom image). T2-weighted images (a,a'), T1-weighted images with gadolinium (b,b'), DWI images (c,c'), apparent diffusion coefficient (d,d'), and SWI images (e,e') are shown from left to right. The 3-month follow-up showed increase in size, more than 25%, of enhancing tumor in the left temporo-mesial area, and progressive extension into the ipsilateral parahippocampal gyrus. T2 signal intensity was similar to the previous MR exam, but contained focal hyperintensities on DWI (corresponding to low ADC values), and multiple black dots on SWI.

Figure 2

Pattern B. MRI changes in recurrent high grade glioma under regorafenib, pattern B. MRI scans performed at baseline (top image) and after six months (bottom image) from the first administration of REG therapy. T2w images (a,a'), contrast enhanced T1w images (b,b'), diffusion-weighted b1000 (c,c'), apparent diffusion coefficients (ADC) map (d,d'), SWI images (e,e'), and color-coded perfusion map (f,f') are shown from left to right. On 6-month follow-up MRI, the previously enhanced tumor component showed a dramatically absence of CE, diffusion restriction on DWI and ADC map, and decrease signal on corresponding T2 image, surrounding by a thin hypointense rim on SWI, and peripheral contrast enhancement on T1-wi after gadolinium. There was also a decrease of peritumoral edema.

Figure 3

Summary table of MRI changes during REG. The patterns defined as A and B are divided into two columns, and the MRI sign changes most frequently reported in the literature have been graphically identified with a thicker cell margin.