Glioblastoma (GBM): Symptoms, Diagnosis, and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Glioblastoma (GBM) is a WHO Grade 4 astrocytoma and the most aggressive primary brain tumor in adults, accounting for approximately 48% of all primary malignant brain tumors. Approximately 15,000 new US cases are diagnosed annually. Median age at diagnosis is 64 years. IDH-wildtype GBM (primary, approximately 90%) occurs in older adults de novo; IDH-mutant GBM (secondary, approximately 10%) arises from lower-grade glioma progression in younger patients and has a better prognosis.

IDH-wildtype GBM is characterized by TERT promoter mutation (approximately 80%), EGFR amplification (approximately 50%), CDKN2A/B homozygous deletion, and chromosome 7 gain with chromosome 10 loss. Ionizing radiation to the head (therapeutic) is the only confirmed environmental risk factor. Hereditary syndromes including Li-Fraumeni syndrome (TP53 germline), Lynch syndrome, and neurofibromatosis type 1 confer elevated risk. No confirmed link to mobile phone use. IDH-mutant GBM shows prior lower-grade glioma progression with IDH1/2 mutation, ATRX loss, and CDKN2A/B homozygous deletion.

GBM presents with rapidly progressive neurological symptoms over weeks to months. Headache (often worse in the morning and with position change), seizures (in approximately 30%), focal neurological deficits (motor weakness, aphasia, visual changes depending on tumor location), personality and cognitive changes, and nausea or vomiting from raised intracranial pressure are common. Confusion, drowsiness, and herniation signs indicate severe ICP elevation. Symptoms typically worsen rapidly due to the aggressive growth pattern of GBM.

MRI with gadolinium is the diagnostic imaging standard: GBM appears as a heterogeneous mass with irregular ring-enhancing margins, central necrosis, and surrounding T2/FLAIR signal edema. Spectroscopy shows elevated choline and reduced NAA. Surgical resection or biopsy provides tissue for WHO 2021 molecular classification: IDH status, TERT promoter, EGFR amplification, chromosome 7 gain/10 loss, MGMT promoter methylation status, H3 K27 and G34 mutations, and CDKN2A/B homozygous deletion. Full neuraxis staging is not routinely required.

Standard treatment (Stupp protocol) for eligible patients: maximal safe surgical resection followed by concurrent temozolomide (75 mg/m2 daily) plus 60Gy radiotherapy in 30 fractions, then 6 cycles of adjuvant temozolomide (150-200 mg/m2). TTFields (Optune) worn greater than or equal to 18 hours per day added to maintenance TMZ improves median OS to 20.9 months (EF-14 trial). Elderly or poor performance status patients: hypofractionated radiation (40Gy in 15 fractions) plus temozolomide (MGMT-methylated) or radiation alone. Bevacizumab for recurrent GBM (improves PFS, not OS). Clinical trials with immunotherapy (nivolumab, pembrolizumab, CAR-T, vaccines) are actively enrolling.

GBM has the poorest prognosis of all glioma subtypes. Median OS with Stupp protocol is approximately 14.6 months; with TTFields added, approximately 20.9 months. Two-year OS is approximately 30% with combined Stupp plus TTFields. Five-year survival is less than 10% for IDH-wildtype GBM. MGMT-methylated GBM has median OS of 21-23 months versus 12-15 months for unmethylated. IDH-mutant grade 4 astrocytoma has a significantly better median OS of 24-31 months. Age, performance status, extent of resection, and MGMT methylation are the strongest independent prognostic factors.

No established environmental risk factors permit preventive strategies for sporadic GBM. Unnecessary cranial irradiation should be avoided, particularly in children. Patients with hereditary predisposition syndromes (Li-Fraumeni, Lynch syndrome) should undergo annual brain MRI surveillance. Research into GBM immunoprevention (vaccines targeting neoantigens) is in early stages. Population-based screening for GBM is not currently recommended due to lack of effective early detection biomarkers. Genetic counseling is warranted for patients with GBM under age 45.