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.
Keywords: Glioma; Proton pseudoprogression; Proton radiation; Pseudoprogression.