Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth and a poor prognosis for patients. Despite advancements in treatment, the median survival time for GBM patients remains low. One of the crucial challenges in understanding and treating GBMs involves its remarkable cellular heterogeneity and adaptability. Central to the survival and proliferation of GBM cells is their ability to undergo metabolic reprogramming. Metabolic reprogramming is a process that allows cancer cells to alter their metabolism to meet the increased demands of rapid growth and to survive in the often oxygen- and nutrient-deficient tumor microenvironment. These changes in metabolism include the Warburg effect, alterations in several key metabolic pathways including glutamine metabolism, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, increased uptake and utilization of glutamine, and more. Despite the complexity and adaptability of GBM metabolism, a deeper understanding of its metabolic reprogramming offers hope for developing more effective therapeutic interventions against GBMs.

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OBJECTIVE: Atypical intracranial meningiomas are characterized by brain invasion and faster growth than lower-grade counterparts. Surgery improves survival for patients with atypical meningiomas, and this study assesses the association between the timing of surgery and survival. METHODS: Patients > 18 years of age with intracranial atypical meningiomas resected (2004–2019) and cataloged in the National Cancer Database were included. Descriptive statistics of sociodemographic and clinical characteristics were generated. Kaplan-Meier survival curves for each variable were generated. Cox proportional hazards models were developed to assess the association of time between diagnosis and surgery with overall survival, while controlling for age, sex, race, ethnicity, facility type, tumor size, comorbidity, resection type, adjuvant radiotherapy, and systemic therapy. RESULTS: A total of 5452 patients were included; 17.81% of the patients were between 18 and 50 years, 66.89% were between 51 and 75 years, and 15.30% were > 75 years. Among the cohort, 55.98% of patients were female. The average time between diagnosis and surgery was 0.8 months; 63.33% of the patients underwent gross-total resection, 28.28% received adjuvant radiotherapy, and 0.92% received systemic therapy. Overall, 21.39% of the patients died during the study period, and the average follow-up time after surgery was 50.9 months. Bivariate analysis showed that the risk of patient mortality over the entire study period increased significantly for every additional month between diagnosis and surgery (hazard ratio [HR] 1.03, 95% CI 1.01–1.06; p = 0.01). On multivariable analysis, a longer time between diagnosis and surgery (HR 1.03, 95% CI 1.00–1.05; p = 0.02) remained a significant predictor of mortality after adjusting for age, sex, race, ethnicity, treatment facility type, tumor size, frailty, resection type, adjuvant radiotherapy, and systemic therapy. On subgroup analysis, delayed time to surgery was associated with increased mortality for those who received subtotal resection (HR 1.04, 95% CI 1.01–1.07; p = 0.01), but not for those who received gross-total resection (HR 1.02, 95% CI 0.97–1.06; p = 0.43). Patients who were female, Asian, treated at an academic program, and received radiotherapy were associated with significantly decreased mortality, whereas patients who were male, African American, had a tumor size > 60 mm, had more comorbidities, and underwent subtotal resection experienced increased mortality. CONCLUSIONS: Additional time between diagnosis and surgery is associated with an increased risk of mortality after adjusting for confounders. The authors recommend surgery as soon as safely possible after diagnosis for patients with intracranial meningiomas with signs of atypia.