Restriction Spectrum Imaging Differentiates True Tumor Progression From Immune-Mediated Pseudoprogression: Case Report of a Patient With Glioblastoma

Abstract

Immunotherapy is increasingly used in the treatment of glioblastoma (GBM), with immune checkpoint therapy gaining in popularity given favorable outcomes achieved for other tumors. However, immune-mediated (IM)-pseudoprogression is common, remains poorly characterized, and renders conventional imaging of little utility when evaluating for treatment response. We present the case of a 64-year-old man with GBM who developed pathologically proven IM-pseudoprogression after initiation of a checkpoint inhibitor, and who subsequently developed true tumor progression at a distant location. Based on both qualitative and quantitative analysis, we demonstrate that an advanced diffusion-weighted imaging (DWI) technique called restriction spectrum imaging (RSI) can differentiate IM-pseudoprogression from true progression even when conventional imaging, including standard DWI/apparent diffusion coefficient (ADC), is not informative. These data complement existing literature supporting the ability of RSI to estimate tumor cellularity, which may help to resolve complex diagnostic challenges such as the identification of IM-pseudoprogression.

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“…He developed pathologically proven pseudoprogression as well as a secondary primary lesion in a separate location. The authors found that RSI was able to differentiate true progression from pseudoprogression while ADC could not ( 204 ). However, whilst RSI is supported by marginally more clinical evidence than these other emerging techniques, it has yet to be adopted in large-scale glioblastoma research studies, thereby allowing the strengths of the technique to be demonstrated.…”

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“…It is possible that FW correction methods, such as the one applied in this study, can be of value in differentiating true disease progression from pseudo-progression [ 44 ]. Tumor cellularity, as derived with RSI, has been presented as a possible diagnostic tool in identifying pseudo-progression in glioblastoma [ 45 , 46 ]. The patients in this study are treatment-naïve; consequently, no pseudo-progression can be measured.…”

Advanced Imaging Techniques for Differentiating Pseudoprogression and Tumor Recurrence After Immunotherapy for Glioblastoma

“…These advantages indicate that RSI-MRI have a good application prospect in the immunotherapy of neurological tumors. In a case report of immunotherapy for GBM, authors demonstrated that RSI could differentiate between pseudoprogression and tumor relapse while conventional DWI imaging could not provide more information ( 36 ). Despite that these advanced DWI techniques can provide better tissue structural characteristics than traditional DWI, the potential pathophysiological mechanism of tumor is still unknown.…”