Molecular features of intratumoral hemorrhage in glioblastoma isocitrate dehydrogenase-wildtype.

BACKGROUND: Glioblastoma isocitrate dehydrogenase (IDH)-wildtype (GBM) has been reclassified based on molecular and phenotypic features. Intratumoral hemorrhage is a phenotypic subtype with poorly understood molecular and clinical characteristics. We aimed to characterize the molecular profile and outcomes of hemorrhagic glioblastoma (hGBM) compared with non-hGBM. METHODS: A retrospective analysis of GBMs with pre-operative and post-operative MRI and comprehensive next-generation sequencing of 205 genes was performed. Patients were classified as hGBM or non-hGBM using the Visually Accessible Rembrandt Images criteria. Univariable and multivariable survival analyses were performed. Genes were compared using the Fisher-exact test and corrected for multiple comparisons with the Benjamini-Hochberg method. RESULTS: 176 patients were included, of whom 105 had hGBM. Compared to non-hGBMs, hGBMs were more likely Hispanic (20.0% vs. 7.0%, p = 0.018), presented with motor deficits (38.0% vs. 21.1%, p = 0.020), and had larger tumors (147.6 cm3 vs. 122.2 cm3, p = 0.034). In addition, hGBMs harbored less frequently PDGFRA (13.3% vs. 26.8%, p = 0.031), KIT (8.5% vs. 19.7%, p = 0.040), KDR (6.6% vs. 18.3%, p = 0.027), or PIK3R1 (2.8% vs. 11.3%, p = 0.030) alterations, and a higher frequency of SETD2 alterations (8.5% vs. 1.4%, p = 0.050). These differences were not significant after multiple comparison corrections. No differences in progression-free survival (8.2 vs. 8.3 months, p = 0.337) or overall survival (18.4 vs. 19.7 months, p = 0.800) were identified by hemorrhagic status. CONCLUSIONS: hGBMs might be associated with lower frequencies of PDGFRA, KIT, KDR, and PIK3R1 alterations and higher frequencies of SETD2 alterations compared to non-hGBMs. No outcome differences were observed by intratumoral hemorrhage status in this cohort.