A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.ABBREVIATIONS: BTIP = Brain Tumor Imaging Protocol; CE = Contrast-Enhancing; CNS = Central Nervous System; CR = Complete Response; ECOG = Eastern Cooperative Oncology Group; HGG = High-Grade Glioma; IDH = Isocitrate Dehydrogenase; IRF = Independent Radiologic Facility; LGG = Low-Grade Glioma; KPS = Karnofsky Performance Status; MR = Minor Response; mRANO = Modified RANO; NANO = Neurological Assessment in Neuro-Oncology; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PFS = Progression-Free Survival; PR = Partial Response; PsP = Pseudoprogression; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; RT = Radiation Therapy; SD = Stable Disease; Tx = Treatment.

Advanced Imaging in the Diagnosis and Response Assessment of High-Grade Glioma: AJR Expert Panel Narrative Review.

This AJR Expert Panel Narrative explores the current status of advanced MRI and PET techniques for the post-therapeutic response assessment of high-grade adult-type gliomas, focusing on ongoing clinical controversies in current practice. Discussed techniques that complement conventional MRI and aid the differentiation of recurrent tumor from post-treatment effects include DWI and diffusion tensor imaging; perfusion MRI techniques including dynamic susceptibility contrast (DSC), dynamic contrast-enhanced MRI, and arterial spin labeling; MR spectroscopy including assessment of 2-hydroxyglutarate (2HG) concentration; glucose- and amino acid (AA)-based PET; and amide proton transfer imaging. Updated criteria for Response Assessment in Neuro-Oncology are presented. Given the abundant supporting clinical evidence, the panel supports a recommendation that routine response assessment after HGG treatment should include perfusion MRI, particularly given the development of a consensus recommended DSC-MRI protocol. Although published studies support 2HG MRS and AA PET, these techniques' widespread adoption will likely require increased availability (for 2HG MRS) or increased insurance funding in the United States (for AA PET). The article concludes with a series of consensus opinions from the author panel, centered on the clinical integration of the advanced imaging techniques into posttreatment surveillance protocols.

Imaging and diagnostic advances for intracranial meningiomas.

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.

Glioma response assessment: Classic pitfalls, novel confounders, and emerging imaging tools.

Neuroimaging plays a pivotal role in the care of patients with infiltrating gliomas, in whom imaging changes are often the first indications of tumor response or progression. Unfortunately, evaluation of glioma response is often not straightforward, even for experienced radiologists. Post-surgical or radiation-related changes may mimic the appearance of disease progression, while medications such as corticosteroids and antiangiogenic agents may mimic tumor response without truly arresting tumor growth or improving patient survival. Immunotherapy response can result in inflammatory changes which manifest as progressively increasing tumor enhancement and edema over months. Many of these pitfalls can be minimized or avoided altogether by the use of modern brain tumor response criteria, while others will require new imaging tools before they can be fully addressed. Advanced MRI methods and novel positron emission tomography (PET) agents are proving important for this purpose, and their role will undoubtedly continue to grow in the future.

Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data.

The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.

Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape.

The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies.