Background: In 2018, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that IDH-wildtype diffuse astrocytic glioma Grade II/III with either EGFR amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or TERT promoter mutation should receive an integrated histological and molecular grade classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The natural history, radiologic characteristics and standard management for these patients has not been well described. They are typically excluded from clinical trials for WHO Grade IV gliomas. Methods: Adults diagnosed at Massachusetts General Hospital with IDH wildtype diffuse astrocytoma and EGFR amplification or TERT promoter mutation from 2011-2019 were identified. Demographics, functional status, radiologic features, MGMT promoter methylation status, time to progression, and overall survival were collected retrospectively. Qualitative MRI data was analyzed using the VASARI feature set. Response assessment was performed using the RANO criteria. Results: 50 patients were identified (table). 37/50 patients received standard Stupp protocol, 2/50 received hypofractionated radiotherapy with temozolomide, 6/50 received radiotherapy alone, and 1 patient received a MEK inhibitor. None were enrolled in clinical trials at diagnosis. mPFS was 10 months in the 47/50 with confirmed progression and mOS in the patients with confirmed deaths (40/50) was 17.5 months (4-47). 9/50 patients are alive with survival ranging 6-52 months. Conclusions: Outcomes for patients with molecularly defined GBM were variable. Analysis of the cohort to characterize factors that led to the observed variability is in progress. More studies on molecularly defined glioblastomas are required to better understand their behavior and to provide guidance for their inclusion or exclusion in clinical trials.