Glioblastoma multiforme GBM
40% of all cancers spread to the brain
To hear that a loved one has been diagnosed with a glioblastoma multiforme (GBM) is devastating, as this type of tumour is aggressive and incurable. The location of the tumour will determine whether surgery is possible and standard treatment includes chemotherapy and radiotherapy. While the prognosis can be very dire, some patients defy the odds. Our supporter Richard Preston was diagnosed in 2013.
What is glioblastoma multiforme?
Glioblastoma multiforme (GBM) is a fast-growing type of tumour of the brain or spinal cord. It is the most common type of primary malignant brain tumour in adults.
GBMs almost never spread outside of the brain, spine or central nervous system to other parts of the body. They are very challenging to treat because of their complex nature, which is why a great deal of research in the UK and around the world is focused
on this tumour type.
GBMs are highly varied tumours that contain a mixture of different types of "glial" brain cells, hence the name glioblastoma and “multiforme” meaning “highly variable”. Cell types within these tumours are variably specialised and they closely interact with normal brain cells such as astrocytes, oligodendrocytes, microglia and cells of the blood vessels.
The makeup of the tumour cells varies both in terms of genetic mutations (lesions affecting the DNA in specific genes) and the resulting activity of the affected genes. This is called “heterogeneity”, which translates as “diversity”, “variability” or “composed of dissimilar cells”.
Glioblastoma is a grade 4 brain tumour - a classification assigned by the World Health Organisation (WHO) - on the basis of the histology (how it looks under the microscope) of a tumour sample (biopsy). The way that a tumour looks on a brain scan can also indicate the type and grade of a tumour, but is not as reliable as looking at the cells themselves.
A small percentage of patients are diagnosed with multifocal and multicentric glioblastoma, meaning there is more than one focal point within the brain for the tumour.
Latest research indicates that GBMs are unlikely to develop from fully formed brain cells, but instead develop from immature cells or stem cells which suffered DNA damage at some point in their life during their development from a stem cell to a progenitor cell and/or a mature brain cell.
The complexity, diversity and rapid growth of a GBM tumour means it is very difficult for researchers to develop treatments that can be effective for a patient with this diagnosis.
Multifocal and multicentric glioblastoma
On an MRI scan, this type of glioblastoma can be seen to have multiple areas of high-grade cancerous formations joined together by other abnormal brain tissue. This type of GBM accounts for 2-20% of all glioblastoma tumours.
A multicentric glioblastoma is considered to be more than one GBM tumour that has arisen in the brain at the same time, or within a very short timeframe. It shows up on an MRI scan as more than one area of active brain tumour with areas of apparently normal brain tissue between them.
What is the prognosis for glioblastoma multiforme (GBM)?
The average survival time is devastatingly short – just 12-18 months. However, 25% of glioblastoma patients survive more than one year and 5% of patients survive more than five years. The reason why some people survive so much longer than others is not yet clear.
What is the treatment for glioblastoma?
Surgery is the first option for the treatment of a GBM, usually followed by radiotherapy and chemotherapy.
The surgical operation to remove a GBM is a delicate balancing act between removing as much of the tumour as possible and protecting the function of the healthy brain, so the location of your brain tumour is very important with regard to both the potential impact of surgery and the symptoms that you experience (because different areas of the brain control different mental and physical processes).
A neurosurgeon is limited as to how much of a glioblastoma they can remove because GBMs are “diffuse”, meaning that tumour cells invade healthy areas of the brain adjacent to the tumour.
Part of the skill of a neurosurgeon is for them to judge how much of a tumour is safe to remove without damaging the healthy brain, which is why clinicians may sometimes recommend that part or all of the operation be undertaken as an awake craniotomy.
Unfortunately the diffuse nature of GBM explains why some tumour cells will almost always be left behind and hence will continue to grow.
For this reason, radiotherapy and chemotherapy are the next stages of treatment for a GBM. Usually, people are offered the chemotherapy drug Temozolomide alongside radiotherapy, and then further doses of Temozolomide afterwards.
Pathologists can undertake genetic profiling of GBM tumours. This examination can provide a unique profile of the individual tumour.
The following information can be gleaned as a result of molecular profiling:
IDH status - IDH stands for “Isocitrate Dehydrogenase.” This is an enzyme involved in the production of energy by brain tumour cells, and in GBM it may have a mutation which confers a better prognosis. Research has indicated that different forms of GBMs have differences between these enzymes, though their role in tumour initiation (how a tumour first begins) and tumour growth is still being explored. As part of this research, a number of drugs that can potentially influence IDH enzymes are being investigated.
IDH 'wild' type status - This occurs in about 90% of GBM brain tumours and usually indicates that the tumour formed as glioblastoma since the very beginning (primary GBM) and carries a worse prognosis than those classified as being IDH mutant.
IDH mutant - This represents approximately 10% of GBMs, and indicates a secondary glioblastoma tumour, meaning that it was previously a lower grade glioma and carries a better prognosis than a 'wild' type status.
IDH NOS - This stands for “Not Otherwise Specified”, meaning that in rare cases, it cannot be determined whether a GBM is 'wild' type or mutant for IDH.
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.
1p/19q deletion - The word “deletion” refers to the fact that when you look at one of the chromosomes, the genes at positions 1p and 19q are missing. Tumours with a 1p/19q deletion may respond better to certain chemotherapy drugs such as Temozolomide or Carmustine, than other tumours without the deletion.
How can we find a cure for glioblastoma?
Research we are funding across all of our Centres of Excellence will help lead towards finding a cure for GBM.
Pioneering research at our Brain Tumour Research Centre of Excellence at Queen Mary University of London is focused on using GBM stem cells to help develop unique, patient-specific treatments. Find out more.
The team of researchers 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 GBM metabolism and help in the effective treatment and management of living with this brain tumour. They are also studying the influence of arginine deprivation on GBM cells and are working towards a clinical trial to investigate this further. Find out more.
Our team at the University of Plymouth Centre of Excellence has identified a range of mutations in brain tumour cells that initiate tumour progression and drive growth, potentially transforming slow-growing low-grade gliomas into more immediately life threatening high-grade gliomas, which include GBM. Find out more.
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 GBM.