Glioma

What is a glioma brain tumour?

A glioma is a type of brain tumour that has developed from cells that should have become healthy glial cells in the brain. Glioma brain tumours vary across the spectrum of low-grade (slow-growing) to high-grade (faster-growing).

The stage 4 glioma survival rate is lower than the survival rate for a stage 1
glioma, as higher grades have a poorer prognosis than lower grades.

Glial cells form a web of connective tissues to support the neurons (nerve cells) within the brain and spinal cord. Types of glial cells include astrocytes, oligodendrocytes, microglia and ependymal cells.

According to the 2021 World Health Organization (WHO) classification, there are three main types of adult glioma, including:

astrocytoma, IDH mutant

oligodendroglioma, IDH mutant

glioblastoma, IDH wildtype

What causes a glioma brain tumour?

No single, definitive cause has yet been identified for brain tumours. Some risk factors have been identified, but due to the complex and unique health history for each patient, scientists are still unable to answer this fundamental question.

When glial cells form a glioma tumour, damage can be seen in the DNA and, for example, they no longer undergo apoptosis, which means programmed or purposeful cell death.

We need to fund more research in order to understand how gliomas and other brain tumours are caused.

How are gliomas treated?

The treatment of gliomas, including glioblastoma, involves a multidisciplinary approach that may include surgery, radiation therapy and chemotherapy. The specific treatment plan depends on factors such as the type and grade of the glioma, its location within the brain and the overall health of the patient.

Here is an overview of the primary treatment modalities:

Surgery

The goal of surgery is to remove as much of the tumour as possible while preserving essential brain functions.

In some cases, a neurosurgeon may perform a resection to cut out the tumour. However, complete removal might be challenging or ill-advised, especially if the tumour is located in critical or inaccessible areas of the brain.

Radiation Therapy

Radiation therapy is often used to target remaining tumour cells after surgery or to treat tumours that cannot be surgically removed.

External Beam Radiation is when high-energy beams are directed at the tumour from outside the body. Brachytherapy involves radioactive material being placed directly into or near the tumour.

Chemotherapy

Chemotherapy may be used in addition to surgery and radiation as adjuvant therapy to target remaining cancer cells.

Temozolomide is an oral chemotherapy drug commonly used in the treatment of glioblastoma.

Targeted Therapy

Targeted therapies aim to interfere with specific molecules involved in the growth and progression of cancer cells.

Bevacizumab is an anti-angiogenic drug which may be used to inhibit the formation of new blood vessels that supply the tumour.

Immunotherapy

Immunotherapy is an evolving area of research, aiming to harness the body's immune system to recognize and attack cancer cells.

Checkpoint Inhibitors are drugs that target immune checkpoints, enhancing the body's ability to mount an immune response against the tumour.

Clinical Trials

Participation in these may provide access to experimental treatments and contribute to the advancement of glioma research.

Ongoing research explores new drugs and treatment strategies to improve outcomes for patients with gliomas.

Supportive Care

Glioma treatment may have side effects and supportive care is essential to manage symptoms such as pain, seizures, and neurological deficits.

Physical and occupational therapy may be employed to help patients regain or maintain functional abilities.

Follow-up Care

Regular follow-up visits are crucial to monitor the patient's condition, assess treatment response, and address any emerging issues.

Imaging studies, such as MRI or CT scans, are often used to monitor for tumour recurrence or progression.

Information on treatments for brain tumours

Is glioma a low-grade (benign) or high-grade (malignant) brain tumour?

The grade of a glioma brain tumour gives an indication as to how the tumour is expected to behave (develop).

All brain and central nervous system (CNS) tumours are divided into four tumour types – grades 1 to 4. These grades are based on cells examined using a microscope as well as genetic and epigenetic changes that are discovered during molecular testing in a laboratory.

Grade 1 glioma (low-grade glioma)
Grade 1 gliomas usually occur in children and teenagers. They are the most slow-growing (low-grade) form of glioma brain tumour and carry the longest prognosis.

The most common form of low-grade glioma is a pilocytic astrocytoma, which rarely progresses to a higher grade and can sometimes be completely removed by surgery.
Grade 2 glioma (low-grade glioma)
Grade 2 gliomas are more common in adults but can also occur in children and teenagers. They are initially a slow-growing (low-grade) form of brain tumour but have a tendency to progress to a higher grade over time – usually a number of years. As prognosis varies between individuals, patients’ clinicians are best placed to advise how long this process may take.

Oligodendroglioma are often classified as grade 2 gliomas.

Grade 2 astrocytoma are sometimes referred to as diffuse astrocytoma because they infiltrate through the brain. This is due to the nature of astrocytoma cells, which reach between and around the neurons.
More about astrocytoma
Grade 3 glioma (anaplastic glioma)
Anaplastic means that the glioma brain tumour cells are dividing rapidly.

Anaplastic gliomas, also called grade 3 gliomas, are classed as an aggressive form of brain cancer. They often spread to other parts of the brain and are more challenging to treat than low-grade gliomas.
Grade 4 glioma (including glioblastoma)
Examples of grade 4 gliomas include astrocytoma grade 4 and glioblastoma.

These are fast-growing, aggressive tumours.

Until recently, astrocytoma grade 4 tumours were considered the same type of tumour as a glioblastoma.

However, in an update from the WHO in 2021, glioblastoma was separated from astrocytoma. This was based on the presence or absence of a mutation in an enzyme called isocitrate dehydrogenase (IDH).

What is the survival rate for glioma?

The survival rate for glioma can vary widely depending on the specific type and grade of the tumour, as well as the individual's age, overall health and other factors.

Glioma is a type of brain tumour that originates in the glial cells, which are the supportive cells in the brain. Gliomas are classified by grade, ranging from grade 1 (least aggressive) to grade 4 (most aggressive).

According to the American Brain Tumor Association, the five-year survival rate for glioma varies widely, depending on the grade and other factors, but ranges from 5% to 95%. Specifically:

Grade 1 gliomas (such as pilocytic astrocytoma) generally have a very good prognosis, with a five-year survival rate of around 95%.

Grade 2 gliomas (such as diffuse astrocytoma) have a five-year survival rate of around 40-50%.

Grade 3 gliomas (such as anaplastic astrocytoma) have a five-year survival rate of around 25-30%.

Grade 4 gliomas (such as glioblastoma) are the most aggressive and have a five-year survival rate of around 5-10%.

It's important to note that survival rates are statistical averages and do not necessarily reflect an individual's prognosis. Each person's situation is unique and their specific prognosis will depend on a variety of factors. It's also important to work closely with a medical team and follow their recommended treatment plan.

Why are there different names for different types of glioma brain tumours?

All glioma brain tumours tend to be named to reflect the type of cells that make up the majority of the tumour.

This is determined through a biopsy or a surgical operation where a sample of the tumour is viewed by clinicians through a microscope (known as histopathological assessment) and classified by the physical characteristics that can be observed (known as the phenotype).

Some glioma brain tumours have different names depending upon their grade: for example, they may be called a low-grade glioma or a grade 4 glioblastoma.

Some glioma brain tumours may also be named after the position in which they are primarily growing – for example, a frontal lobe glioma, an optic nerve glioma or a brainstem glioma.

As we learn more about brain tumours, names have sometimes changed to reflect, not only the position and type of cells that they contain, but also the way that the tumour cells are growing and the expected behaviour of the tumour. You may see glioblastoma previously referred to as 'GBM', for example.

As another example, a diffuse intrinsic pontine glioma (DIPG) is the term now commonly used to describe what used to be called a 'high-grade brainstem glioma in children'.

It reflects the fact that the tumour is “diffuse” in nature, meaning that it doesn’t have a clear boundary but instead spreads between and around surrounding brain cells, whilst the “pons” is the lowest, stem-like part of the brain at the top of the spinal cord.

Shared genetic characteristics are examined as part of glioma tumour classification, known as the genotype of a brain tumour.

Is glioma always fatal?

Gliomas are a type of brain tumour that can vary in their aggressiveness and not all gliomas are fatal. However, some gliomas are highly aggressive and can be difficult to treat, which can make them more likely to be fatal.

The prognosis for gliomas depends on several factors, including the specific type and grade of the tumour, its location, the age and overall health of the patient, and the response to treatment. Some types of gliomas, such as low-grade gliomas (for example pilocytic astrocytoma) or certain types of oligodendrogliomas, may have a relatively good prognosis and may be treated successfully with surgery and/or radiation therapy.

Frequently Asked Questions

What is a mixed glioma?

A mixed glioma is a glioma brain tumour that contains a mix of glial cells including astrocytes, oligodendrocytes and ependymal cells.

What is an optic nerve glioma?

An optic nerve glioma is a slow-growing tumour that originates from glial cells along the optic nerve, the pathway connecting the eye to the brain. Primarily diagnosed in children, especially those with neurofibromatosis type 1 (NF1), symptoms may include peripheral vision loss and optic disc swelling. Diagnosis involves eye exams and imaging studies, and treatment varies based on tumour size and symptoms. Small, asymptomatic tumours may be monitored, while larger ones may require surgery, radiation, or chemotherapy. Early detection and a multidisciplinary approach are crucial for managing optic nerve gliomas and preserving vision.

What is molecular testing and what do molecular markers of glioma brain tumours mean?

Current UK guidelines for the classification of gliomas defined by the National Institute for Clinical Excellence (NICE) state that tumours should also be tested for various molecular markers.

These markers include: IDH1 and IDH2 mutations, ATRX mutations, 1p/19q codeletion to identify oligodendrogliomas, Histone H3.3 K27M mutations in midline gliomas and BRAF fusion and gene mutation to identify pilocytic astrocytoma.

In addition, clinicians should test all high-grade glioma specimens for MGMT promoter methylation to inform prognosis and guide treatment. They should also consider testing IDH-wildtype glioma specimens for TERT promoter mutations to inform prognosis.

IDH1 and IDH2 status
IDH stands for “Isocitrate Dehydrogenase”. This is an enzyme involved in the production of energy by brain tumour cells. Research has indicated that different forms of gliomas have differences between these enzymes, though their exact role is still being explored, as are drugs that can potentially influence IDH enzymes.

IDH 'wild' type status
Glioma tumours that have IDH-wildtype status are classified as glioblastoma tumours. These grade 4 brain tumours are fast growing and aggressive.

IDH mutant
Glioma tumours that are IDH mutant are likely to either be an astrocytoma (astrocytoma, IDH-mutant) or an oligodendroglioma (oligodendroglioma, IDH-mutant). These can be classified as grades 1-4 depending on the patient’s tumour.

ATRX mutations
The ATRX gene provides instructions for making a protein that plays an essential role in normal brain development. If the ATRX protein is mutated and doesn’t function properly, it can contribute to the development of certain types of glioma brain tumour.

IDH NOS
This stands for “Not Otherwise Specified”, meaning that in rare cases, it cannot be determined whether a tumour is 'wild' type or mutant for IDH.

1p/19q deletion
This refers to missing genes on chromosomes and tumours with this “deletion” may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine.

Histone H3.3 K27M mutations in diffuse midline gliomas
A histone is a type of protein that is found in chromosomes and mutations in this protein can help identify diffuse midline gliomas and guide treatment.

BRAF fusion and gene mutation in pilocytic astrocytoma
The BRAF gene can become fused with a number of different proteins, or undergo other mutations that are found in pilocytic astrocytoma brain tumours. In particular, the fusion of BRAF and KIAA1549 proteins is a diagnostic marker for this tumour type.

MGMT methylation
This is short for O6-methylguanine-DNA methyltransferase and whether it is 'methylated' or 'unmethylated' indicates how effectively the tumour cells can repair the damage inflicted on them by certain chemotherapy drugs, such as Temozolomide. Patients with higher levels of MGMT methylation respond better to Temozolomide treatment. Methylation means the transfer of a methyl group (CH3) from one molecule to another, which affects the way the tumour behaves.

TERT promoter mutations in glioma brain tumours
TERT stands for telomerase reverse transcriptase. It is an enzyme that affects telomere length in human cancers including glioma. Telomeres are structures at the end of chromosomes that can indicate expected lifespan.

Unfortunately, long relative telomere length combined with TERT-promoter mutations indicate that the glioma is likely to be resistant to radiotherapy and hence the prognosis is worse than for gliomas without this genetic marker.

Can a glioma be cured?

The ability to cure a glioma depends on several factors, including the type and grade of the tumour, its location, and the patient's age and overall health.

Low-grade gliomas (such as pilocytic astrocytoma) and some types of oligodendrogliomas may be more curable than other types of gliomas. In some cases, these tumours may be removed surgically and may not require further treatment.

However, high-grade gliomas (such as glioblastoma) are more difficult to cure. These tumours tend to grow quickly and spread aggressively, and they may be resistant to treatment. While surgery, radiation therapy, and chemotherapy can help slow the growth of these tumours and prolong survival, they are generally not curative.

How can we find a cure for gliomas?

Research we are funding across all of our Centres of Excellence will help lead towards finding a cure for glioma brain tumours.

Pioneering research at our Brain Tumour Research Centre of Excellence at Queen Mary University of London is focused on using glioblastoma stem cells to help develop unique, patient-specific treatments.

Our team at the University of Plymouth Brain Tumour Centre of Excellence are researching a range of mutations in brain tumour cells that initiate tumour progression and drive growth, transforming slow-growing low-grade gliomas into high-grade gliomas. Their discoveries are designed to enable new treatments to be developed and tested in order to halt and hopefully reverse this process. The team are also testing combination therapies for low-grade brain tumours, designed to enhance the effectiveness of existing treatments.

The team of research and clinical experts at our Centre of Excellence at Imperial College, London, are part of a global collaboration looking at how the ketogenic diet can influence glioma metabolism and help in the effective treatment and management of living with this brain tumour.

We also fund BRAIN UK at Southampton University, the country’s only national tissue bank registry providing crucial access to brain tumour samples for researchers from all clinical neuroscience centres in the UK, effectively covering about 90% of the UK population, and an essential component in the fight to find a cure for glioma brain tumours.