Glioblastoma

Glioblastoma is the most aggressive and most common type of cancerous brain tumor in adults, growing rapidly and invading healthy brain tissue. Despite treatment with surgery, radiation, and chemotherapy, this devastating disease typically recurs and remains one of the most challenging cancers to treat.

Table of contents

• What is Glioblastoma?
• Signs and Symptoms
• Causes and Risk Factors
• How Common is Glioblastoma?
• Diagnosis
• Treatment Options
• Outlook and Survival

What is Glioblastoma?

Glioblastoma is a type of cancer that starts as a growth of cells in the brain or spinal cord. It grows quickly and can invade and destroy healthy tissue^[1]. Glioblastoma (GBM), previously known as glioblastoma multiforme, is the most aggressive and most common type of cancer that originates in the brain^[4].

Glioblastoma forms from cells called astrocytes, which are star-shaped cells that support nerve cells in the brain and spinal cord^[1]. These supporting cells, also called glial cells, are responsible for various roles including providing nutrients to neurons, maintaining the blood-brain barrier, and helping with communication between nerve cells^[2]. When these cells become cancerous, they multiply rapidly and are frequently supported by an extensive network of blood vessels^[6].

Although glioblastomas occur almost exclusively in the brain, they can also appear in the brain stem, cerebellum, and spinal cord^[5]. About 61% of all primary gliomas occur in the four lobes of the brain: the frontal lobe (25%), temporal lobe (20%), parietal lobe (13%), and occipital lobe (3%)^[5]. While glioblastoma is highly invasive within the brain, it typically does not spread to other organs in the body^[7].

Signs and Symptoms

Symptoms of glioblastoma vary depending on the location of the tumor in the brain. Many symptoms result from increased pressure in the brain as the tumor grows larger and takes up space, compressing healthy brain tissue within the fixed volume of the skull^[15]. Initial signs and symptoms are often nonspecific, meaning they can be similar to those of other conditions^[4].

Common symptoms include:

• Persistent headaches, particularly those that hurt the most in the morning^[1]
• Nausea and vomiting^[1]
• Confusion or decline in brain function, such as problems with thinking and understanding information^[1]
• Memory loss^[1]
• Personality changes or irritability^[1]
• Vision changes, such as blurred vision, double vision, or loss of peripheral vision^[1]
• Speech difficulties^[1]
• Trouble with balance or coordination^[1]
• Muscle weakness in the face, arms, or legs^[1]
• Reduced sensation of touch or numbness^[1]
• Seizures, especially in someone who hasn’t had seizures before^[1]

Glioblastoma symptoms tend to come on quickly. Symptoms often worsen rapidly and may progress to unconsciousness^[4]. Symptoms similar to those of a stroke may also occur^[4]. More specific symptoms depend on the location of the tumor and the functions affected. For example, glioblastoma near the motor cortex (the part of the brain involved in body movement) may cause loss of movement or sensation on one side of the body, while tumors near the language regions may cause problems with speech^[15].

Causes and Risk Factors

The cause of most cases of glioblastoma is not known^[4]. Researchers suggest that changes in DNA lead to the development of glioblastoma brain tumors. Genes contain DNA and give instructions to cells about how to grow and multiply. Mutations, or changes, to the DNA in genes can cause cells to multiply out of control^[2].

Most commonly, these mutations happen randomly during a person’s lifetime rather than being inherited from biological parents. However, it is possible to inherit genetic variations, though inherited glioblastomas are rare^[2].

Several factors may increase the risk of developing glioblastoma:

• Age: Glioblastoma most often affects people ages 45 to 70, with the average age at diagnosis being 64 years^[4][5]
• Gender: The disease occurs more commonly in males than females^[4]
• Race: Incidence is slightly higher in Caucasians relative to other ethnicities^[5]
• Previous radiation therapy to the head^[4]
• Exposure to chemicals, such as pesticides, petroleum, synthetic rubber, and vinyl chloride^[2]
• Genetic conditions: Uncommon risk factors include genetic disorders such as neurofibromatosis, Li-Fraumeni syndrome, Lynch syndrome, and Turcot syndrome^[2][4][6]

How Common is Glioblastoma?

Glioblastoma is the most common type of malignant (cancerous) brain tumor in adults^[2]. It represents 15% of all brain tumors^[4] and accounts for about 47.7% of all malignant brain and central nervous system tumors^[6].

About 3 in 100,000 people develop the disease per year^[4]. The average age-adjusted incidence rate is 3.2 per 100,000 population^[5]. According to estimates, about 13,000 to 15,000 Americans are diagnosed with glioblastoma every year^[2][8].

Glioblastomas present at a median age of 64 years but can occur at any age, including childhood^[5]. Incidence is slightly higher in men than women^[5]. Recently, however, the disease is beginning to be seen more commonly in younger adults under the age of 40^[8].

Diagnosis

The diagnosis of glioblastoma typically involves a combination of examinations and tests. A healthcare provider will evaluate symptoms and perform a neurological exam, which checks vision, hearing, balance, coordination, strength, and reflexes. Problems in one or more of these areas might give clues about the part of the brain the glioblastoma affects^[10].

If a brain tumor is suspected, imaging tests are used to find the location and size of the glioblastoma:

• MRI (Magnetic Resonance Imaging): This is the most important imaging test used most often for glioblastoma^[6][10]. Usually, images are acquired both before and after administration of a contrast dye through an injection in a vein. If the tumor picks up the contrast (becomes bright on images), this is an indication of a higher-grade tumor^[6].
• CT scan (Computed Tomography): This test can also help pinpoint the location of brain tumors^[6][10].
• PET scan (Positron Emission Tomography): This imaging test may also be used^[10].

However, an MRI alone cannot confirm a diagnosis. Other conditions, such as strokes, infections, or different types of tumors, can look similar^[18]. To confirm the diagnosis, a biopsy is necessary. This is a procedure to remove a sample of tissue for testing. It can be done with a needle before surgery or during surgery to remove the glioblastoma^[10].

The tissue sample is sent to a lab where tests can tell whether the cells are cancerous and if they’re glioblastoma cells. Special tests of the cancer cells, including examination under a microscope and molecular testing, give the healthcare team more information about the glioblastoma^[10]. The specialist doctor (pathologist) will do tests to look for specific genetic changes in the tumor cells, such as mutations in the IDH gene and MGMT methylation status^[9].

The World Health Organization classifies glioblastomas as grade 4 tumors, the most aggressive type. Glioblastomas are now called “glioblastoma, IDH wildtype,” meaning they do not have mutations in the IDH gene^[9][15].

Treatment Options

Glioblastoma treatment is multimodal, meaning it involves several different approaches. The current standard of care typically consists of four main pillars^[11]:

Surgery

Treatment usually begins with surgery when possible^[1]. The primary goals of surgery are to collect a tissue sample for diagnosis, remove as much of the tumor as possible while protecting critical brain function (called “maximal safe resection”), and alleviate symptoms caused by the tumor^[15].

The neurosurgeon works to remove as much of the brain tumor as possible without negatively affecting the brain’s neurologic functions^[11]. However, surgery isn’t always an option. For example, if the glioblastoma grows deeper into the brain, it might be too risky to remove all of the cancer^[10]. High-grade brain tumors cannot be removed entirely by surgery because microscopic cells often remain, and the tumor will eventually grow back^[11].

Radiation Therapy

To slow down the growth of tumor cells, surgery is typically followed by six weeks of treatment which includes radiation therapy^[11]. Standard radiation therapy is typically given in 30 fractions (30 days) of treatment over a period of six weeks^[11].

Radiation therapy uses X-rays and other sources to kill tumor cells. It is delivered by a machine called a linear accelerator from outside the body and aims only at the area of the brain that contains the tumor^[11]. Recent advances include the use of proton beam therapy, a cutting-edge, nonsurgical form of radiation therapy that destroys cancer cells with targeted precision while minimizing side effects to surrounding healthy tissue^[13].

Chemotherapy

Temozolomide (TMZ), also known as Temodar, is an oral chemotherapy pill and the only FDA-approved therapy with a survival benefit for adult patients with glioblastoma^[11][4]. It is taken at home for 42 days, starting along with radiation therapy. This is typically followed by six monthly cycles, though up to 12 cycles may be given^[11].

Tumor Treating Fields (TTFields)

Optune is an FDA-approved wearable and portable device for adults with glioblastoma that delivers Tumor Treating Fields (TTFields)^[11]. TTFields are low intensity, alternating electrical fields that interfere with cancer cell division, which slows or stops cancer cells from dividing and may destroy them^[11]. Patients wear electrodes on the scalp for approximately 18 hours a day^[14].

Supportive Care

High-dose steroids (also called corticosteroids) may be used to help reduce swelling around the tumor and decrease symptoms^[4]. Medications may also be needed to control seizures^[2].

Clinical Trials and Emerging Therapies

Because standard treatments have limited effectiveness, many patients participate in clinical trials testing new approaches. Innovative treatments being studied include immunotherapy, gene therapy, and targeted drugs to attack specific molecular features of the tumor^[5][14].

Outlook and Survival

Glioblastoma has a very poor prognosis. The typical duration of survival following diagnosis is 10 to 13 months with treatment^[4][13]. Without treatment, survival is typically three months^[4].

Approximately 40% of patients survive in the first year after diagnosis, with 17% surviving into the second year^[6]. Fewer than 5 to 10% of people survive longer than five years^[4][5]. Recent studies using the most current standard of care, including tumor-treating fields, report median survival of about 21 months^[19].

Despite maximum treatment with aggressive surgical removal and combined radiation and chemotherapy, the cancer almost always recurs^[4][5]. Once the tumor recurs, it is always fatal^[7].

Several factors can affect prognosis. Patients with certain genetic features in their tumors, such as MGMT methylation, may respond better to chemotherapy and have improved survival^[9]. Younger age and better overall health at diagnosis are also associated with longer survival^[5].

Glioblastoma is a devastating cancer that drastically impacts independence, level of functioning, and quality of life^[19]. However, research continues to advance, and new therapies offer hope for improved outcomes in the future. Some patients and families also seek to make lifestyle adjustments, such as dietary changes, exercise, and stress management, which may help improve quality of life^[19].