Glioblastoma (GBM)

What glioblastoma is

Glioblastoma is a type of glioma, a tumor arising from the brain's glial (supporting) cells. Under the World Health Organization's 2021 classification, glioblastoma is defined as a diffuse astrocytic glioma that is IDH-wildtype (no IDH mutation) with aggressive features. Tumors with an IDH mutation that look similar are now classified as grade 4 astrocytoma, which has a better outlook, and oligodendroglioma is a separate, slower-growing glioma.

Glioblastoma cells spread microscopically into surrounding brain, beyond what scans can see. That is why surgery alone cannot cure it and why it almost always recurs.

Symptoms

Symptoms usually develop over weeks to a few months:

• headache, often worse in the morning, with nausea or vomiting, caused by raised pressure inside the skull
• seizures, in about a quarter to a third of people at diagnosis
• personality and behavior change, apathy, confusion, poor concentration
• memory problems
• weakness or numbness on one side
• speech or language difficulty
• vision changes, including loss of part of the visual field
• drowsiness in advanced cases

Symptoms depend on the tumor's location; see brain tumor for how location shapes symptoms. Frontal lobe tumors may first appear as personality change that family members notice.

Causes and risk factors

Most glioblastomas have no known cause. Established risk factors are:

• age: most common between 55 and 75
• male sex (slightly more common)
• previous radiation to the head
• rare inherited syndromes such as Li-Fraumeni syndrome, Lynch syndrome and neurofibromatosis type 1

Mobile phones, head injuries and diet have not been shown to cause glioblastoma.

Diagnosis

1. Neurological examination.
2. MRI with contrast: typically shows an irregular, ring-enhancing mass with a dead (necrotic) center and surrounding swelling.
3. Surgery or biopsy: confirms the diagnosis.
4. Molecular testing: IDH status (to separate glioblastoma from IDH-mutant astrocytoma), MGMT promoter methylation (which predicts better response to temozolomide), and other markers such as EGFR amplification and TERT mutation.

Treatment

Surgery

The first step is maximal safe resection: removing as much of the tumor as possible without harming critical brain functions. Fluorescent dyes (such as 5-ALA), intraoperative MRI and awake surgery with brain mapping help. If the tumor is in a deep or critical area, a biopsy may be done instead.

Radiation and chemotherapy (Stupp protocol)

After surgery, standard treatment is about 6 weeks of daily radiation with temozolomide chemotherapy taken by mouth, followed by 6 or more cycles of temozolomide alone. Older or frail patients may receive a shorter radiation course.

Tumor-treating fields

A wearable device applies electric fields to the scalp, disrupting cancer cell division. Used with temozolomide after radiation, it has been shown to extend survival modestly.

At recurrence

Options include repeat surgery, re-irradiation, lomustine or other chemotherapy, bevacizumab (which reduces swelling and symptoms), and clinical trials of immunotherapy, targeted drugs, vaccines and other approaches.

Supportive care

• dexamethasone (a steroid) to reduce brain swelling
• anti-seizure medicines for those who have had seizures
• rehabilitation: physical, occupational and speech therapy
• palliative care from diagnosis, to manage symptoms and support quality of life
• psychological support for patients and families; help with driving rules, work and legal planning

Prognosis

Glioblastoma remains one of the hardest cancers to treat:

• median survival with standard treatment is about 15 to 20 months, longer with tumor-treating fields in some studies
• about 5 to 7 percent of people survive 5 years or longer
• younger age, better physical function, more complete removal and MGMT methylation are linked to longer survival

These are averages. Individual outcomes vary, and some people live many years. See brain cancer for an overview of other malignant brain tumors and their outlook.

Clinical trials

Because current treatments are limited, many experts encourage people with glioblastoma to ask about clinical trials at diagnosis and at recurrence. Major cancer centers and the National Cancer Institute list open trials.

Frequently asked questions

What are the first symptoms of glioblastoma?

Early symptoms often include headaches that worsen over weeks, seizures, personality or behavior changes, memory or concentration problems, and gradual weakness, numbness or speech difficulty. Symptoms depend on where the tumor is in the brain.

What is the life expectancy with glioblastoma?

With standard treatment, median survival is about 15 to 20 months, and around 5 to 7 percent of people live 5 years or longer. Younger age, good overall health, extensive surgery and MGMT methylation are linked to better outcomes.

Is glioblastoma curable?

Currently it is very rarely curable, because tumor cells spread into surrounding brain beyond what surgery and radiation can reach. Treatment aims to control the tumor, extend life and maintain quality of life. Clinical trials are testing new approaches.

What is stage 4 glioblastoma?

Brain tumors are graded rather than staged. Glioblastoma is always a grade 4 tumor, the most aggressive grade, because of its fast growth and features under the microscope. It rarely spreads outside the brain.

What causes glioblastoma?

In most people, the cause is unknown. It arises from gene changes in glial cells that build up over time. The only established environmental risk factor is previous radiation to the head. Rare inherited syndromes raise the risk slightly.