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What is Glioblastoma Multiforme?

By November 12, 2018December 14th, 2020No Comments

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor of the central nervous system. GBM arises from a specific type of glial cell called astrocytes, which support the survival and function of the surrounding neurons. The World Health Organization (WHO) grades gliomas on a scale of I-IV based on the degree of histopathologic atypia observed. GBM receives the most malignant designation, WHO Grade IV, for the presence of many abnormal, actively dividing cells, new vessel growth, and necrosis (Louis, Acta Neuropathol, 2016).

GBM is relatively rare, with a worldwide incidence of less than 10 cases per 100,000 people (Hanif, Asian Pac J Cancer Prev, 2017). Nonetheless, the impact of GBM is profound – they are largely incurable with only 5-10% of patients surviving five years after diagnosis (Chien, Front Public Health, 2016). With such a poor prognosis and relatively few effective interventions, new therapies are desperately needed to improve outcomes and survival.

The symptoms of GBM are relatively non-specific and often depend on the size and location of the tumor. In general, symptoms can include headache, seizure, and focal neurologic deficits that correlate with tumor location, such as weakness, language deficits, and cognitive impairment (Chang, JAMA, 2005). Ultimately, GBM is usually detected by MRI and officially diagnosed by tissue biopsy, which can occur during surgical removal of the tumor or during a separate procedure (Glioma, Mayo Clinic).

The clinical course of GBM patients depends on several factors intrinsic to the tumor itself. GBM can develop from a pre-existing, lower grade brain tumor called an astrocytoma or can arise de novo. These GBM subsets differ in their underlying pathogenesis and in disease phenotype. Sporadic GBM are the most common subtype, comprising 90% of all GBM. They typically present later in life, develop much more rapidly, and have an overall worse prognosis (Ohgaki & Kleihues, Am J Pathol, 2007; Ohgaki & Kleihues, Clin Cancer Res, 2013).

GBM is typically managed by a combination of surgical resection, radiation, and chemotherapy. When possible, gross total resection with preservation of neurologic function is the preferred intervention, as it confers a more favorable outcome than subtotal resection (Noorbakhsh, J Neurosurg, 2014). After surgical intervention, most patients are treated with adjuvant radiation and chemotherapy, specifically with the alkylating agent temozolomide. Response to temozolomide largely depends on the methylation status of the MGMT gene (Zhao, World J Surg Oncol, 2016). Methylated MGMT prevents DNA repair in response to alkylating agents, allowing the tumor cell to accumulate more damage and be sensitized to chemotherapy. Presence of MGMT methylation improves overall survival by about 50% (Zhao, World J Surg Oncol, 2016).

It is important to keep in mind that GBM has a poor prognosis regardless of tumor subtype and genetic makeup. The survival benefit conferred by any one beneficial prognostic factor is a matter of months. While this can, of course, be meaningful to patients, there is a clear opportunity for improvement upon the current standard of care in order to prolong survival and improve quality of life.