GBM

GBM
Name	GBM
Field	Neurology, Oncology
Symptoms	Headache, seizures, focal neurological deficits
Complications	Cognitive decline, motor dysfunction
Onset	Adult
Causes	Somatic mutations, chromosomal alterations
Risks	Advanced age, prior ionizing radiation
Diagnosis	MRI, histopathology, molecular profiling
Treatment	Surgery, radiotherapy, temozolomide, tumor-treating fields
Medication	Temozolomide, bevacizumab (palliative)
Prognosis	Median survival ~12–18 months

GBM is an aggressive primary brain tumor characterized by rapid growth, heterogeneity, and poor prognosis. It predominantly affects adults and commonly arises in the cerebral hemispheres, producing mass effect, seizures, and progressive neurological deficits. Multimodal management combines neurosurgical resection, radiotherapy, and chemotherapy, while molecular profiling guides prognosis and emerging targeted approaches.

Overview

GBM presents as a high-grade astrocytic neoplasm with infiltrative behavior that complicates complete surgical removal. Notable historical and institutional milestones in care include advances at Memorial Sloan Kettering Cancer Center, developments influenced by trials at Mayo Clinic and MD Anderson Cancer Center, and contributions from researchers affiliated with National Institutes of Health and Dana–Farber Cancer Institute. Key frameworks for classification evolved through consensus by groups such as the World Health Organization and standards implemented in cohorts studied at Johns Hopkins Hospital and UCLA Medical Center.

Signs and symptoms

Presenting features often reflect tumor location and mass effect, including progressive headaches, new-onset seizures, cognitive changes, and focal deficits such as weakness or aphasia. Clinical encounters frequently involve specialists from American Academy of Neurology and referrals to centers like Cleveland Clinic and Massachusetts General Hospital. Acute deterioration may lead to emergency management protocols similar to those used in Boston Children’s Hospital stroke pathways and neurocritical care units at Bellevue Hospital.

Pathophysiology and genetics

Tumorigenesis involves somatic alterations in signaling pathways and chromatin regulators, with hallmark changes in genes such as TP53, PTEN, and amplification of receptor tyrosine kinases. Molecular subsets originally delineated through projects at The Cancer Genome Atlas and laboratories at Broad Institute include patterns associated with EGFR amplification, IDH wild-type or mutant status, and TERT promoter mutations. Chromosomal aberrations and epigenetic modifications described by investigators at Cold Spring Harbor Laboratory and Salk Institute contribute to intratumoral heterogeneity and therapy resistance.

Diagnosis

Initial evaluation relies on neuroimaging with MRI protocols refined by radiology departments at Stanford Health Care and NYU Langone Health, often supplemented by diffusion and perfusion sequences. Definitive diagnosis requires histopathological assessment by neuropathologists from centers such as Royal Marsden Hospital and molecular testing for markers including isocitrate dehydrogenase and MGMT promoter methylation—assays standardized in laboratories at Mayo Clinic Molecular Diagnostics and Quest Diagnostics. Multidisciplinary tumor boards at institutions like Memorial Sloan Kettering Cancer Center integrate findings to plan management.

Treatment

First-line management emphasizes maximal safe surgical resection performed by neurosurgeons trained at institutions such as Cleveland Clinic and UCLA Medical Center, followed by fractionated radiotherapy protocols developed at MD Anderson Cancer Center combined with concurrent and adjuvant temozolomide per regimens influenced by trials at EORTC and RTOG. Tumor-treating fields, commercialized after research at Novocure, provide an adjunct for selected patients. Bevacizumab has been used palliatively following studies at Memorial Sloan Kettering Cancer Center and Dana–Farber Cancer Institute to address edema. Supportive care often involves rehabilitation teams from Shirley Ryan AbilityLab and palliative services modeled at St. Christopher's Hospice.

Prognosis and epidemiology

Prognosis remains guarded, with median survival around 12–18 months in population series compiled by registries like the Surveillance, Epidemiology, and End Results Program and outcomes reported from national cohorts in United Kingdom and Sweden. Favorable prognostic indicators include younger age, extent of resection achieved at centers such as Cleveland Clinic, and molecular features like IDH mutation and MGMT promoter methylation identified in studies from The Cancer Genome Atlas. Incidence increases with age and has been characterized in epidemiological analyses performed by Centers for Disease Control and Prevention researchers.

Research and experimental therapies

Ongoing research spans targeted therapies, immunotherapies, oncolytic viruses, and precision medicine initiatives pioneered at institutions including Broad Institute, Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, and UCSF Medical Center. Clinical trials conducted through cooperative groups such as NRG Oncology and Alliance for Clinical Trials in Oncology evaluate combinations of checkpoint inhibitors, CAR T-cell strategies, vaccine platforms, and novel small molecules. Translational efforts from laboratories at Cold Spring Harbor Laboratory and Salk Institute aim to overcome intratumoral heterogeneity and the blood–brain barrier challenges that were studied in foundational work at Massachusetts General Hospital and Stanford University School of Medicine.

Category:Brain neoplasms