MRI in Glioma Immunotherapy: Evidence, Pitfalls, and Perspectives

Abstract

Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology) criteria, including conventional MRI (cMRI), addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015. In spite of this, the unequivocal definition of glioma progression by cMRI remains difficult particularly in the setting of immunotherapy approaches provided by checkpoint inhibitors and dendritic cells. Advanced MRI (aMRI) may in principle address this unmet clinical need. Here, we discuss the potential contribution of different aMRI techniques and their indications and pitfalls in relation to biological and imaging features of glioma and immune system interactions.

Figure 1

FLAIR (a–e) and contrast-enhanced T1-weighted images (f–j): postsurgical (a, f), increasing edema (b, c), enhancement (g, h) and subsequent reduction (d, e, i) of both, and remission of the enhancing lesion (j) in the course of immunotherapy with dendritic cell vaccine.

Figure 2

Contrast-enhanced T1-weighted images (a–f) and the calculated TRAM postchemoradiation (g–l) (images were acquired 0.7, 2.5, 4, 6, 7, and 8 months postchemoradiation). Temporary enlargement of enhancing lesion (c-d) is shown; as it can be seen, the red volume growth rate was prevalent above the blue volume (i-j), favoring pseudoprogression over progression. Pseudoprogression was later confirmed by the decrease in all volumes 7 and 8 months postchemoradiation (e-f, k-l). Modified from [110] with permission.

Figure 3

MRS during immunotherapy, after surgery, and radiotherapy plus temozolomide. Left, spectra; right, voxel positioned within enhancing lesions. (a) High Cho and low NAA with minimum lipids in recurrent glioma. (b) Preserved Cho and NAA levels with evident though not prevalent lipid peak in pseudoprogression (the same case is shown in Figure 1—time point Oct 2014). (c) Prominent peak of lipids and lower peaks of Cho, Cr, and NAA but with high Cho/Cr and Cho/NAA ratios in mixed scenario with glioma recurrence and radionecrosis.

Figure 4

Enhancing lesion (a) during immunotherapy with dendritic cell vaccine. Mismatch between T1-enhancing volume and CBV (b), the last being just slightly elevated; permeability (K_trans) is increased (c). ADC is low (d), suggesting hypercellularity.