Abstract

Abstract PURPOSE Radiologic Assessment in Neuro-Oncology (RANO) criteria define pseudoprogression (Ps) after photon radiation for gliomas, as occurring less than twelve weeks from radiation, within the high dose radiation field. However, some patients receiving proton manifest lesions that appear subjectively different from photon Ps based on timing and location (more than six months from radiation and deeper to the prior tumor), which would be called tumor progression by RANO. We retrospectively reviewed MRI changes after proton or photon radiation for gliomas. We propose criteria to characterize proton pseudoprogression (ProPs) distinct from photon pseudoprogression or tumor progression. METHODS Post-treatment MRIs of patients with gliomas were reviewed, along with clinical and pathological data. 77 proton patients were reviewed for the presence of ProPs, and 64 photon patients were reviewed for imaging changes. Data collected included the location, timing, and morphology of the lesions, tumor type, chemotherapy, and clinical symptoms. RESULTS 16 (21%) of the patients who received protons had imaging changes unique to protons, at a mean of 14.6 months after radiation. We established the following criteria to characterize ProPs: not immediately in or adjacent to the resection cavity; ~ 2cm opposite from target beam entry; can resolve without treatment; subjectively multifocal, patchy, small (< 1cm). None of the photon patients had lesions that met our criteria for ProPs (p< 0.001). CONCLUSION Patients who receive protons can have a unique subtype of pseudoprogression (Ps), which we refer to as proton pseudoprogression (or ProPs). These lesions could be mistaken for tumor progression, but typically resolve spontaneously. ProPs can possibly be explained by the increased relative biological effectiveness of protons and beam angle selection which may deposit at ~2cm deep to the target. Recognizing these lesions can prevent unnecessary treatment for mistaken tumor progression, especially in the context of clinical trials that include proton.

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