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    Glioblastoma Multiforme and Genetic Mutations: The Issue Is Not Over Yet. An Overview of the Current Literature

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    BACKGROUND AND OBJECTIVE: Glioblastoma multiforme (GBM) is still a deadly disease with a poor prognosis and high mortality, despite the discovery of new biomarkers and new innovative targeted therapies. The role of genetic mutations in GBM is still not at all clear; however, molecular markers are an integral part of tumor assessment in modern neuro-oncology. MATERIAL AND METHODS: We performed a Medline search for the key words "glioblastoma," "glioblastoma multiforme," and "genetic" or "genetics" from 1990 to the present, finding an exponential increase in the number of published articles, especially in the past 7 years. RESULTS: The understanding of molecular subtypes of gliomas recently led to a revision of the World Health Organization classification criteria for these tumors, introducing the concept of primary and secondary GBMs based on genetic alterations and gene or protein expression profiles. Some of these genetic alterations are currently believed to have clinical significance and are more related to secondary GBMs: TP53 mutations, detectable in the early stages of secondary GBM (found in 65%), isocitrate dehydrogenase 1/2 mutations (50% of secondary GBMs), and also O6-methylguanine-DNA methyltransferase promoter methylation (75% of secondary GBMs). CONCLUSION: From the introduction of the first standard of care (SOC) established in 2005 in patients with a new diagnosis of GBM, a great number of trials have been conducted to improve the actual SOC, but the real turning point has never been achieved or is yet to come. Surgical gross total resection, with at least one more reoperation, radiation therapy plus concomitant and adjuvant temozolomide chemotherapy currently remains the current SOC for patients with GBM

    Clinical risk and overall survival in patients with diabetes mellitus, hyperglycemia and glioblastoma multiforme. A review of the current literature

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    The relationship between type 2 diabetes mellitus (DM2) and hyperglycemia with cancer patients remains controversial also in the setting of patients with glioblastoma multiforme (GBM), the most common and aggressive form of astrocytoma with a short overall survival (OS) and poor prognosis. A systematic search of two databases was performed for studies published up to 19 August 2020, reporting the OS of patients with DM2 or high blood sugar level and GBM and the clinical risk of diabetic patients for development of GBM. According to PRISMA guidelines, we included a total of 20 papers reporting clinical data of patients with GBM and diabetes and/or hyperglycemia. The aim of this review was to investigate the effect of DM2, hyperglycemia and metformin on OS of patients with GBM. In addition, we evaluated the effect of these factors on the risk of development of GBM. This review supports accumulating evidence that hyperglycemia, rather than DM2, and elevated BMI are independent risk factors for poor outcome and shorter OS in patients with GBM. GBM patients with normal weight compared to obese, and diabetic patients on metformin compared to other therapies, seems to have a longer OS. Further studies are needed to understand better these associations
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