Distinct imaging patterns of pseudoprogression in glioma patients following proton versus photon radiation therapy.

PURPOSE: Criteria by the Radiologic Assessment in Neuro-Oncology (RANO) group outline the diagnosis of pseudoprogression (Ps) after photon therapy for gliomas based on timing and location. We noted that patients receiving proton therapy manifested radiographic changes that appear different than Ps after photon therapy, which could be interpreted as tumor progression. In this study, we retrospectively reviewed MR imaging after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) as distinct from Ps seen after photons. METHODS: Post-treatment MR imaging, clinical and pathological data of low grade glioma patients were reviewed. Overall, 57 patients receiving protons were reviewed for the presence of ProPs, and 43 patients receiving photons were reviewed for any equivalent imaging changes. Data collected included the location and timing of the new enhancement, tumor grade, molecular subtype, chemotherapy received, and clinical symptoms. RESULTS: Fourteen patients (24.6%) had new enhancement following radiation therapy that was unique to treatment with protons. The mean time to development of the ProPs was 15.4 months (7-27 months). We established the following criteria to characterize ProPs: located at the distal end of the proton beam; resolves without tumor-directed therapy; and subjectively multifocal, patchy, and small (< 1 cm). In the group receiving photons, none had changes that met our criteria for ProPs. CONCLUSION: Patients who receive protons have unique imaging changes after radiation therapy. ProPs could be mistaken for tumor progression, but typically resolves on follow up. Further studies are needed to understand the radiobiology and pathophysiology underlying these imaging changes.

Clinical Imaging for Diagnostic Challenges in the Management of Gliomas: A Review.

Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality, it is frequently insufficient to inform clinical decision-making. There is a need for noninvasive strategies for reliably distinguishing low-grade from high-grade gliomas, identifying important molecular features of glioma, choosing an appropriate target for biopsy, delineating target area for surgery or radiosurgery, and distinguishing tumor progression (TP) from pseudoprogression (PsP). One recent advance is the identification of the T2/fluid-attenuated inversion recovery mismatch sign on standard MRI to identify isocitrate dehydrogenase mutant astrocytomas. However, to meet other challenges, neuro-oncologists are increasingly turning to advanced imaging modalities. Diffusion-weighted imaging modalities including diffusion tensor imaging and diffusion kurtosis imaging can be helpful in delineating tumor margins and better visualization of tissue architecture. Perfusion imaging including dynamic contrast-enhanced MRI using gadolinium or ferumoxytol contrast agents can be helpful for grading as well as distinguishing TP from PsP. Positron emission tomography is useful for measuring tumor metabolism, which correlates with grade and can distinguish TP/PsP in the right setting. Magnetic resonance spectroscopy can identify tissue by its chemical composition, can distinguish TP/PsP, and can identify molecular features like 2-hydroxyglutarate. Finally, amide proton transfer imaging measures intracellular protein content, which can be used to identify tumor grade/progression and distinguish TP/PsP.