glioblastoma

glioblastoma
Name	Glioblastoma
Synonyms	Glioblastoma multiforme, GBM, grade IV astrocytoma
Caption	Axial MRI scan showing a glioblastoma (bright area) in the right parietal lobe.
Field	Oncology, Neurosurgery, Neuro-oncology
Symptoms	Headaches, seizures, personality changes, neurological deficits
Complications	Increased intracranial pressure, herniation
Onset	Typically in older adults
Duration	Chronic, progressive
Types	Primary, secondary
Causes	Unknown; risk factors include genetic syndromes and ionizing radiation
Risks	Neurofibromatosis type 1, Li-Fraumeni syndrome, prior radiotherapy
Diagnosis	Magnetic resonance imaging, biopsy
Differential	Brain metastasis, primary CNS lymphoma, abscess
Prevention	None known
Treatment	Surgical resection, temozolomide, radiotherapy, tumor treating fields
Medication	Corticosteroids, bevacizumab
Prognosis	Poor; median survival ~15 months with treatment
Frequency	~3 per 100,000 per year
Deaths	Highly fatal

glioblastoma is the most common and aggressive malignant primary brain tumor in adults. It is classified as a World Health Organization grade IV astrocytoma and is characterized by rapid growth and diffuse infiltration into surrounding brain tissue. Standard management involves maximal safe surgical resection followed by concurrent radiotherapy and chemotherapy with temozolomide, yet recurrence is nearly universal and prognosis remains poor.

Overview

Glioblastoma arises from glial cells, specifically astrocytes, within the central nervous system. It can develop *de novo* (primary glioblastoma) or progress from a lower-grade astrocytoma (secondary glioblastoma), with primary tumors being more common in older individuals. The tumor is notorious for its heterogeneous cellular composition, which includes necrotic cores and prominent microvascular proliferation, features evident on histopathological examination. Despite its name "multiforme" being retired in the World Health Organization classification, it remains in widespread colloquial use.

Causes and risk factors

The exact cause of glioblastoma is unknown, and most cases are sporadic. Established environmental risk factors are limited, with exposure to high-dose ionizing radiation, such as from prior radiotherapy for other conditions, being the strongest link. Certain rare genetic syndromes significantly increase lifetime risk, including neurofibromatosis type 1, Li-Fraumeni syndrome, and Turcot syndrome. Studies have not conclusively linked glioblastoma to electromagnetic fields from mobile phones or to specific dietary factors.

Pathophysiology

Glioblastoma is driven by complex genetic and molecular alterations that promote uncontrolled cellular proliferation, invasion, and resistance to apoptosis. Key pathways frequently dysregulated include the receptor tyrosine kinase/RAS/PI3K pathway and the p53 tumor suppressor pathway. The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a critical biomarker influencing response to alkylating agent chemotherapy. The tumor creates a profoundly immunosuppressive microenvironment and exhibits remarkable intratumoral heterogeneity, which complicates targeted therapies.

Diagnosis

Diagnosis typically begins with neuroimaging, most commonly contrast-enhanced magnetic resonance imaging, which reveals a ring-enhancing mass with surrounding vasogenic edema. The definitive diagnosis requires histopathological confirmation via stereotactic biopsy or tissue obtained during craniotomy. The World Health Organization classification integrates molecular parameters, such as isocitrate dehydrogenase mutation status and MGMT promoter methylation, for diagnostic and prognostic stratification. Differential diagnoses include other mass lesions like brain metastasis, primary CNS lymphoma, and cerebral abscess.

Treatment

The standard first-line treatment, established by the Stupp protocol, involves maximal safe surgical resection followed by concurrent radiotherapy and temozolomide, then adjuvant temozolomide. The device delivering tumor treating fields is an approved maintenance therapy. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, is used for recurrent disease to manage edema. Supportive care includes medications like dexamethasone to reduce peritumoral edema and anticonvulsants for seizure control. Clinical trials at institutions like the National Cancer Institute and MD Anderson Cancer Center are integral to care.

Prognosis

Prognosis remains dismal, with a median overall survival of approximately 15 months with standard therapy and a five-year survival rate below 10%. Factors associated with slightly better outcomes include younger age, higher performance status (e.g., Karnofsky Performance Status), MGMT promoter methylation, and complete surgical resection. Nearly all tumors recur, often within 2-3 cm of the original site, leading to progressive neurological decline and death, frequently due to increased intracranial pressure or brain herniation.

Research directions

Current research is focused on overcoming therapeutic resistance and tumor heterogeneity. Major areas of investigation include immunotherapy approaches such as checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and oncolytic viruses. Other strategies involve targeting tumor metabolism, the blood-brain barrier, and specific molecular alterations like epidermal growth factor receptor variants. Large-scale collaborative efforts like The Cancer Genome Atlas have comprehensively mapped its genomic landscape, and consortia such as the Global Coalition for Adaptive Research are designing innovative adaptive clinical trials.

Category:Central nervous system tumors Category:Neuro-oncology Category:Death