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.

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

“…But as with standard therapy, advanced MR such as perfusion imaging has been investigated as a way to identify pseudoprogressors but to date the utility and accuracy required for adoption into the clinical standard of care has not been demonstrated. 65 …”

Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

“…An integrated histologic and molecular diagnosis is strongly prognostic in glioma, with survival ranges between 1 and 15 years (Louis et al, 2016). While surgery continues to be an essential component of initial diagnosis and treatment when feasible, monitoring for tumor recurrence is currently by MRI, which is not sensitive for microscopic disease (Aquino et al, 2017…”

“…Pseudoprogression of brain tumors is defined by radiographic alterations that are due to treatment rather than tumor growth, including increased lesion size, contrast enhancement, and/or edema, in the absence of increased tumor activity. With the advent of immunotherapy, disease monitoring by imaging alone has become increasingly complicated as the tempo and MRI appearance of tumor progression and response can be less predictable with the use of immunotherapy than traditional cytotoxic therapy (Aquino et al, 2017). Although pseudoprogression often resolves on its own, in some cases it progresses to treatment-related necrosis (Brandsma and van den Bent, 2009;Wen et al, 2017).…”

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids

“…During treatment, monitoring of therapeutic response in DMGs is limited to MRI, which lacks sensitivity to detect small changes or tumor genomic evolution. MRI is also prone to detect pseudoprogression, transient inflammation at the site of the tumor that mimics true progression on imaging and may misinform interpretation of tumor response 7 . Thus, DMGs represent a tumor type with a high need for an alternative, minimally invasive means of detecting tumor mutations and monitoring clinical response.…”