Background Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging cancer treatment–related effects. Both phenomena remain insufficiently defined; differentiation from recurrent disease frequently necessitates tissue biopsy. We here characterize distinctive features of PP and TN to facilitate noninvasive diagnosis and clinical management. Materials and Methods Patients with glioma and confirmed PP (defined as appearance <5 months after radiotherapy [RT] completion) or TN (>5 months after RT) were retrospectively compared using clinical, radiographic, and histopathological data. Each imaging event/lesion (region of interest [ROI]) diagnosed as PP or TN was longitudinally evaluated by serial imaging. Results We identified 64 cases of mostly (80%) biopsy‐confirmed PP ( n = 27) and TN ( n = 37), comprising 137 ROIs in total. Median time of onset for PP and TN was 1 and 11 months after RT, respectively. Clinically, PP occurred more frequently during active antineoplastic treatment, necessitated more steroid‐based interventions, and was associated with glioblastoma (81 vs. 40%), fewer IDH1 mutations, and shorter median overall survival. Radiographically, TN lesions often initially manifested periventricularly ( n = 22/37; 60%), were more numerous (median, 2 vs. 1 ROIs), and contained fewer malignant elements upon biopsy. By contrast, PP predominantly developed around the tumor resection cavity as a non‐nodular, ring‐like enhancing structure. Both PP and TN lesions almost exclusively developed in the main prior radiation field. Presence of either condition appeared to be associated with above‐average overall survival. Conclusion PP and TN occur in clinically distinct patient populations and exhibit differences in spatial radiographic pattern. Increased familiarity with both conditions and their unique features will improve patient management and may avoid unnecessary surgical procedures. Implications for Practice Pseudoprogression (PP) and treatment‐induced brain tissue necrosis (TN) are challenging treatment‐related effects mimicking tumor progression in patients with brain cancer. Affected patients frequently require surgery to guide management. PP and TN remain arbitrarily defined and insufficiently characterized. Lack of clear diagnostic criteria compromises treatment and may adversely affect outcome interpretation in clinical trials. The present findings in a cohort of patients with glioma with PP/TN suggest that both phenomena exhibit unique clinical and imaging characteristics, manifest in different patient populations, and should be classified as distinct clinical conditions. Increased familiarity with PP and TN key features may guide clinicians toward timely noninvasive diagnosis, circumvent potentially unnecessary surgical...

Stroke-like migraine attacks after radiation therapy (SMART) syndrome represents a rare but serious condition manifesting years after cranial radiation therapy (RT). 1 Characterized by migraine-type headaches, stroke-like deficits, seizures, and MRI abnormalities, including cortical gyriform enhancement in irradiated brain regions, SMART is diagnostically and therapeutically challenging. [2][3][4][5][6] Distinction from tumor progression is difficult and treatment options are limited. 2 Although frequently reversible, 5 SMART episodes can recur 6 and effectuate persistent neurologic or imaging sequelae. 3 MethodsThis retrospective multicenter study presents 7 patients diagnosed with SMART at Massachusetts General Hospital, Brigham and Women's Hospital, and Dana-Farber Cancer Institute between 2013 and 2020. Patient data were obtained from institutional databases and include portions of 2 previously published cases. 6 Institutional review board approval was granted. Clinicoradiographic features, treatment strategies, and potential pathomechanisms of SMART are discussed. Data AvailabilityAnonymized data will be shared upon request from any qualified investigator.