BACKGROUND AND PURPOSE: Patient survival in high-grade glioma remains poor, despite the recent developments in cancer treatment. As new chemo-, targeted molecular, and immune therapies emerge and show promising results in clinical trials, image-based methods for early prediction of treatment response are needed. Deep learning models that incorporate radiomics features promise to extract information from brain MR imaging that correlates with response and prognosis. We report initial production of a combined deep learning and radiomics model to predict overall survival in a clinically heterogeneous cohort of patients with high-grade gliomas. MATERIALS AND METHODS: Fifty patients with high-grade gliomas from our hospital and 128 patients with high-grade glioma from The Cancer Genome Atlas were included. For each patient, we calculated 348 hand-crafted radiomics features and 8192 deep features generated by a pretrained convolutional neural network. We then applied feature selection and Elastic Net-Cox modeling to differentiate patients into long-and short-term survivors. RESULTS: In the 50 patients with high-grade gliomas from our institution, the combined feature analysis framework classified the patients into long-and short-term survivor groups with a log-rank test P value , .001. In the 128 patients from The Cancer Genome Atlas, the framework classified patients into long-and short-term survivors with a log-rank test P value of .014. For the mixed cohort of 50 patients from our institution and 58 patients from The Cancer Genome Atlas, it yielded a log-rank test P value of .035. CONCLUSIONS: A deep learning model combining deep and radiomics features can dichotomize patients with high-grade gliomas into long-and short-term survivors. ABBREVIATIONS: C-indices 4 concordance indices; CNN 4 convolutional neural network; GBM 4 glioblastoma multiforme; HGG 4 high-grade glioma; OS 4 overall survival; SE 4 spin-echo; TCGA 4 the Cancer Genome Atlas G lioblastoma multiforme (GBM), the largest diagnostic subcategory of high-grade glioma (HGG) and the most common malignant adult brain tumor, afflicts 12,000-13,000 new patients annually in the United States. GBM, comprising a genetically and phenotypically heterogeneous category of tumors, has a