Brain tumour research

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than the treatments that are available at the moment
• They are known to be safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.

Tests in patients are called clinical trials. The trials and research section has information about what trials are including information about the 4 phases of clinical trials. If you are interested in taking part in a clinical trial, go to our searchable database of clinical trials recruiting in the UK. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team.

All the new approaches covered here are the subject of ongoing research. Until studies are completed and new effective treatments are found, these treatments cannot be used as standard therapy for brain tumours.

Cancer Research UK scientists are looking into the differences between the genes in brain tumour cells and normal cells. They have already found some common gene faults and are hoping that investigating these will lead to new ways of diagnosing and treating brain tumours. The National Brain Tumour Study is looking at blood samples from people who have had a brain tumour in the last 5 years to find out more about the genetic causes of brain tumours. They are also looking into how doctors in the future may be able to use the gene changes to tailor treatment to individual patients.

One trial is looking at gene changes in pituitary tumours. The UK CYAB study is a small trial of children and young people up to 24 years old, looking at factors such as diet, lifestyle, and history of infections, to try to find what might cause brain tumours in this age group. 

You can find out more about these trials on our clinical trials database. Choose 'brain tumours' from the dropdown list of cancer types.

Research is looking into improving scans and diagnosis. One recent trial tested a new type of MRI scan called DTI (Diffusor Tension Imaging). It is also sometimes called tractography. Standard MRI can’t show up important bundles of white nerve fibres. Damage to these white nerve bundles during surgery can have serious effects. Surgeons have to find out where these nerves are and if they are surrounded by the tumour. They can then avoid cutting through the nerve bundles. The research team found that DTI scans are useful for getting a more detailed picture of the brain than other types of scan. They also found they could see the difference between nerve bundles, normal tissue and areas of tumour more clearly. The researchers say that it is early days for this new technique, but it may be useful for planning treatment in the future.

The only sure way to diagnose many brain tumours is to have a biopsy done. Looking at the cells under a microscope is the only guaranteed way to identify the type and grade of the tumour. The CNS 2004 10 trial and the CNS 2004 11 trial are looking at a newer less invasive technique to help diagnose brain tumours. It is a type of scan called magnetic resonance spectroscopy (MRS) and doesn’t involve having an operation. MRS is a procedure similar to an MRI scan. But as well as giving a picture of the tumour, MRS also gives doctors information about the activity of the brain tissue. 

With information from MRS doctors are able to identify the type and grade of a brain tumour. It also helps them to tell the difference between a brain tumour and other brain disorders such as epilepsy and infections. MRS is still very experimental. We need a lot more research before we will know exactly how reliable and accurate this procedure is. Until we have this, biopsy is still the best method of diagnosing a brain tumour. The UK trials aim to find out if MRS can help in the diagnosis and management of teenagers and children with brain tumours or brain stem tumours.

The advanced MRI scan trial is looking at whether specialised MRI scans can help to decide how and when to treat brain tumours. The new types of MRI scan give information about the size and shape of the tumour. They also show up the blood flow in the brain as well as which chemicals are in the brain, and how they move around.

The above trials are listed on our clinical trials database. To find them, go to the trials database search page and type in 'scans' in the free text search box.

The GALA 5 trial is looking at 2 treatments for glioblastoma. The first treatment is 5-ALA or Gliolan. It is a dye that makes brain tumour cells glow red under ultra violet light. During surgery, it can help surgeons to check they are removing as much brain tumour as possible. The second part of the treatment is a chemotherapy implant called a Gliadel wafer that the surgeon puts into the space left by removing the brain tumour. The aim of this treatment is to kill any tumour cells left after surgery.

The researchers want to see if it is safe to have 5-ALA and Gliadel wafers with standard brain tumour treatments. They also want to find out how many people are helped by this treatment and whether it has an effect on other treatments they have. 

You can find out about this trial on our clinical trials database. Type 'Gala' into the text search box.

Researchers are looking into the following radiotherapy treatments

• Stereotactic radiotherapy and radiosurgery
• Cyberknife
• Boron neutron capture therapy (BCNT)
• Proton therapy
• Hyperfractionated radiotherapy

Stereotactic radiotherapy and radiosurgery

Stereotactic radiotherapy is a technique that gives very accurate and high doses of radiation directly into the centre of the brain tumour without damaging the normal surrounding brain tissue. A variation on this is called radiosurgery, which is a single, highly targeted dose of stereotactic radiotherapy. You might hear radiosurgery being called gamma knife treatment, but the gamma knife is actually the name of one of the machines used to deliver this type of treatment. There is more information about stereotactic radiotherapy and radiosurgery in this section of CancerHelp UK.

Both stereotactic radiotherapy and radiosurgery are still being researched. They are mainly used for brain tumours that have come back or for other cancers that have spread to the brain. They are used for some non cancerous (benign) tumours of the brain, such as acoustic neuroma.

This type of treatment is only suitable for a small number of malignant brain tumours and for particular circumstances. It is less likely to be suitable for larger tumours or for widespread tumours. There are a number of clinical trials in progress in the USA and other parts of the world. When the results from these are available, specialists will know more. For now, they are not part of standard treatment for most people with a primary brain tumour. 

Cyberknife

Cyberknife is a new type of targeted radiotherapy. it is given by a machine that does not need a frame to keep you still during treatment. It also has built in imaging, so it can continually adjust for any slight movements you might make, by regularly scanning the area. This special equipment allows doctors to target the radiotherapy beams very exactly at the tumour and not damage the surrounding healthy body tissues. The Cyberknife computer controls robotic arms, which give the radiation. The arms move to give the radiation from different angles. The bed that you lie on can also move to position you correctly. Cyberknife is used for some spinal tumours and for some people who have multiple brain metastases. There is information about cyberknife in our question and answer section.

Boron neutron capture therapy (BNCT)

BCNT is an experimental way of giving radiotherapy. It has been tried in trials with glioblastoma multiforme (grade 4 glioma) and has been used widely in Japan. There are concerns about the levels of side effects of the treatment, so more research is being done in Europe and the USA. The researchers are looking into using this treatment after surgery to try to reduce the risk of the brain tumours coming back. With BNCT, you have boron injections with a low dose of fast neutron therapy. The boron collects in the brain tumour cells and gives off radiation when the fast neutrons hit. 

There is detailed information about BNCT in the brain tumour question and answer section of Cancer Help UK. There is a UK trial looking at giving a drug called Boron Phenylalanine (BPA) that may help BNCT to kill more cancer cells and give less side effects. It makes brain tumour cells more sensitive to radiation and is being used for people with a glioblastoma multiforme brain tumour. The trial aims to find out how BPA affects the body, what the side effects are, the best way of giving BPA and the best dose. 

Proton therapy

One of the newer ways of giving radiotherapy uses a different type of beam called a proton beam. Protons collect energy as they slow down and travel through the body. They then release this energy at their target point – the tumour. This means they give a very high dose of radiation to the cancer, but only a low dose to the area around it. So there is less likelihood of damage to nearby healthy tissue.

Proton beam radiotherapy machines in the UK are only able to treat cancer of the eye. The machines are not able to treat cancers deeper in the body. Some countries in Europe and the USA are testing and using proton beam radiation for deeper cancers, including brain stem cancers and a type of spinal cord cancer called chordoma. At the moment there aren’t any plans to develop proton beam radiotherapy more widely in the UK. If this treatment is suitable for you the NHS pays to send you for treatment abroad – usually to Switzerland or France, but sometimes to the USA.

Hyperfractionated radiotherapy

The HIT - SIOP PNET trial is testing whether 2 radiotherapy treatments a day are better than 1. The trial is for children and young people from the age of 4 to 21 with medulloblastoma. Researchers want to find out if hyperfractionated radiotherapy (HFRT) with 2 treatments a day kills more cancer cells than standard radiotherapy. The aim of the trial is to find out whether HFRT is better at stopping the cancer from coming back. And which treatment has the fewest side effects.

The radiotherapy trials mentioned here are listed on our searchable clinical trials database. Choose 'brain tumours' from the dropdown menu of cancer types.

There are always clinical trials testing new combinations or single chemotherapy drugs for brain tumours. Trials also look at drug doses and the order in which you have them (the sequence). Current research is looking at 

• Temozolamide
• Chemotherapy in young people with gliomas
• High dose chemotherapy
• Chemotherapy for primary lymphoma of the central nervous system (CNS)

Temozolamide

In June 2007, the National Institute for Health and Clinical Excellence (NICE) recommended temozolomide chemotherapy as a possible treatment for newly diagnosed glioblastoma multiforme. Trials have looked at giving temozolamide for 6 months after surgery. The EORTC 26052-22053/RTOG 0525 trial is looking at whether some patients with glioblastoma multiforme would benefit from having temozolomide for longer, up to a year.

Another trial called the BR13 trial is looking at whether temozolomide works better than radiotherapy to treat low grade gliomas. It recruited people who had a grade 2 oligodendroglioma or astrocytoma (the most common type of glioma) which cannot be successfully treated by surgery alone. All these trials have now finished recruiting and we are waiting for the results.

The BR14 trial is looking at radiotherapy with and without temozolomide for anaplastic glioma. Anaplastic means that the cancer cells look less like normal glial cells than other gliomas. Anaplastic cancers often grow more quickly than other cancers. In this trial, some people won’t have temozolomide. Some will have temozolomide during radiotherapy and some will have it after radiotherapy. Some will have it both during and after radiotherapy. Some people with a brain tumour have changes in two chromosomes called 1p and 19q in the cell. One or both must be normal in everyone taking part in this trial. Doctors call this ‘non 1p/19q deleted anaplastic glioma’.The aims of this trial are to find out if temozolomide during radiotherapy, after radiotherapy or both during and after radiotherapy is better than radiotherapy alone. And more about the side effects. 

Chemotherapy in young people

So far, most of the later stage research into chemotherapy and brain tumours has been for the more aggressive types of brain tumour, such as glioblastoma. The SIOP - LGG 2004 CNS 2004 03 trial is looking at giving etoposide in addition to standard chemotherapy for low grade gliomas  in children and teenagers. The trial is also testing giving the chemotherapy for longer than a year to see if this will help stop the tumour regrowing. The CNS 2001 04 trial is looking at whether etoposide can help to treat children and young people with ependymoma that has not been completely removed or has come back after treatment.

The CNS 2007 04 trial is looking at treatment for children and young people (up to 21 years old) with diffuse pontine glioma. This is a type of glioma that starts in the brainstem, the part of the brain that joins the spinal cord. Diffuse pontine glioma is usually treated with radiotherapy. This trial is to find out if adding temozolomide chemotherapy to the radiotherapy will help to shrink the tumour, and to find out what the side effects of combining the treatments are. The trial has closed and we are waiting for the results.

The SIOP 99 trial is trying to find out if cyclophosphamide, vincristine and etoposide chemotherapy helps children and young people with ependymoma when it is given with radiotherapy after surgery. The CNS 2001 06 trial is trying to find out whether adding vincristine chemotherapy to radiotherapy works better than radiotherapy alone for young people aged 4 to 21 with medulloblastoma. These trials have closed now and we are waiting for results.

These chemotherapy trials are listed on our clinical trials database. To find them, go to the trials database search page and choose ‘brain’ from the drop down menu of cancer types.

High dose chemotherapy

The PNET-CNS 2000 01 trial is looking at high dose chemotherapy followed by a stem cell transplant for children and teenagers with a primitive neuroectodermal tumour (PNET) that has come back. High dose chemotherapy is a very experimental treatment and only being used in a small number of hospitals throughout the world. It uses drugs that can cross the natural barrier between the blood circulation and the brain tissue (the blood-brain barrier). 

To have this treatment, some of your blood cells are collected and frozen. Then you are given such high doses of chemotherapy that your bone marrow cells are killed off. To replace them, your own frozen cells are thawed and given back to you. This treatment is also called stem cell transplant or stem cell rescue. There is detailed information in the CancerHelp UK cancer treatment section. This is a very high risk procedure because you will be without white blood cells for a few days or weeks and so will be at a very high risk from infections. This trial has closed and we are waiting for the results.

Chemotherapy for primary lymphoma of the central nervous system (CNS)

Primary CNS lymphoma is a very rare form of non Hodgkin's lymphoma which usually only affects the brain. The first treatment for it is usually the chemotherapy drug methotrexate. Doctors think higher doses of methotrexate would work better, but it has serious side effects, including kidney damage and a reduction in blood cell counts. A drug called glucarpidase helps your body to break down methotrexate quickly and get rid of it. Doctors hope that this will protect you from the worst of the side effects of methotrexate, and allow them to give higher doses to fight the lymphoma. A small trial of this treatment is being done to see how safe it is to give higher doses of methotrexate with glucarpidase, and what the side effects will be.

Biological therapies are treatments that use natural substances from the body, or drugs made from these substances to treat cancer. Research is looking into 

• Cancer growth blockers
• Blood supply and brain cancer
• Monoclonal antibodies
• Gene therapy
• Vaccines

Cancer growth blockers

Some biological therapy drugs called tyrosine kinase inhibitors (TKIs) block signals that tell cancer cells to divide and grow. Imatinib (Glivec) is a TKI drug that works well in treating a type of cancer called gastro intestinal stromal tumour (GIST). Researchers have tried this drug for glioma brain tumours. But the results so far have been mixed, and further trials are needed to see if imatinib is helpful for brain tumours.

Another TKI drug being tested is erlotinib (Tarceva). The Phase 1 NAG 2005 09 trial is looking at how well this might work for children whose brain tumours have continued to grow or have come back after treatment, and for children newly diagnosed with brain stem gliomas, which are very difficult to treat. This trial has now finished recruiting patients and we are waiting for the results.

The DORIC trial is comparing a combination of cediranib and gefitinib (Iressa) with cediranib alone in people who have glioblastoma that has come back after treatment. Cediranib is a type of biological therapy that stops the cancer growing new blood vessels (see the section on blood supply and brain cancer below). Gefitinib is a tyrosine kinase inhibitor. The aim of this trial is to find out if the combination of cediranib and gefitinib works better than cediranib alone for glioblastoma that has come back after treatment.

Blood supply and brain cancer

Angiogenesis means growth of new blood vessels. A cancer needs to grow its own blood vessels as it gets bigger. Without its own blood supply, it can't continue to grow. Anti angiogenic drugs stop tumours from developing their own blood vessels. This then deprives the cancer of the oxygen and food that it needs. Research using these drugs is ongoing for brain cancers. The drug being tried most in trials for brain cancer is thalidomide. Thalidomide hit the headlines in the 1960s when it was discovered that it caused birth defects by cutting down on blood flow to developing limbs in babies in the womb. Since then it has been given to many people with cancer, without causing serious side effects. It is still important not to take this drug if there is any possibility you could be pregnant. Early studies show some promise for treating people with high-grade gliomas. But we will need a lot more research to develop this further as a treatment.

The phase 1 EORTC 26054 trial is looking at the combination of temozolomide with an antiangiogenic drug called enzastaurin, for people with advanced glioma, or newly diagnosed glioma that cannot be treated with radiotherapy. Doctors want to find out how well these drugs work together. This trial has closed and we are waiting for the results.

Monoclonal antibodies

Many different monoclonal antibodies (MABs) are being investigated for cancer treatment. MABs are proteins, made in the laboratory from a single copy of a human antibody. When these laboratory made antibodies are injected into patients they seek out cancer cells which carry abnormal proteins. Some researchers are looking at a MAB called bevacizumab (Avastin) for some types of secondary brain tumour.

Gene therapy

A number of new gene therapy treatments are being researched. Some doctors and researchers are now using the term 'molecular therapy' which is a more general term. It can include research into

• Oncogenes
• Tumour suppressor genes
• Gene therapy and repair genes

By studying how changes in these genes cause normal cells in the brain to become cancerous, scientists aim to eventually develop gene therapy where damaged genes in the cancer cells can be replaced with normal ones.

Doctors have started to look into a gene therapy called cerepro. One trial used a variation of the herpes simplex virus to deliver gene therapy to people with high grade glioma that has come back or started to grow again since treatment. Another trial has looked at using cerepro after surgery. You can find information about cerepro in our brain tumour question and answer section.

Vaccines

There is a phase 1 trial testing a vaccine for glioblastoma. This trial is looking at a new vaccine called IMA950 for people who have just been diagnosed with a glioblastoma brain tumour. This is a new experimental treatment that helps the immune system to kill cancer cells. Researchers are giving it alongside standard treatment of surgery and radiotherapy. People in the trial also have a drug called GM-CSF which helps to stimulate the immune system. Doctors hope this will make the vaccine work better.

If you would like to look for current brain tumour trials, you can look on our clinical trials database and choose ‘brain’ from the dropdown menu of cancer types.

Clomipramine is a drug used for depression, called a tricyclic anti depressant. Some researchers think it might help to treat glioma brain tumours. There has been some lab research that showed the drug could encourage death of cancer cells, but not healthy brain cells. The researchers say this is encouraging.  But there will be a lot more research needed before we know whether this drug can help to treat gliomas.  There have been no trials reported using clomipramine in people with brain tumours and we are not aware of any trials currently recruiting patients.

Tamoxifen is a type of hormone therapy. This drug is most often used to treat or prevent breast cancer. But it has also been tried for other cancers, including brain tumours. How it works on brain tumours is complex. One theory is that because this drug helps to protect against spread of the cancer to the brain for women with breast cancer, it will have a similar protective effect on people with certain types of brain tumours. Much higher doses are needed for people with brain tumours than for women with breast cancer. Researchers think that they need to get a large amount of this drug into the brain in a short time. So they are investigating starting with small doses and increasing the dose fairly quickly. We still don’t know whether people should remain on these high doses or if they should have a lower ‘maintenance’ dose. We also don’t know how long people with a brain tumour would need to carry on taking tamoxifen.

Generally, tamoxifen has few side effects, although it may have more in the high doses used for brain tumours. There is some evidence to suggest that it should not be taken with the anti-epileptic drug called phenytoin. Results from early clinical trials have shown that tamoxifen does not help everyone with a brain tumour but it may help a few. We’ll need larger clinical trials before we will know whether it can help to treat brain tumours.

Photodynamic therapy (PDT) is a type of treatment that makes cells light sensitive and then shines a very bright light onto them. In March 2009, the National Institute for Health and Clinical Excellence (NICE) said that there is not yet enough evidence to recommend this as a standard treatment for brain tumours, and it should only be used as part of clinical trials. 

PDT treatment has been tried for brain tumours that have come back after standard treatment. But now there is a trial testing PDT for some newly diagnosed tumours, including high grade gliomas, secondary brain cancers and cancerous tumours of the pituitary gland. The trial is looking at whether it is better to have PDT as well as surgery and radiotherapy, when you are first treated. People on this trial had either surgery then radiotherapy, or surgery, PDT and radiotherapy. The trial has closed and we are waiting for the results.

There is a trial comparing different laser wave lengths in PDT for the most common types of brain tumour (glioblastoma multiforme or anaplastic astrocytoma). This trial is looking at giving PDT after surgery for brain tumours. The aim is to kill any cells left behind. The trial team are comparing 2 different PDT laser wave lengths. One shines deeper into brain tissue than the other. Doctors want to know which wave length of laser is better at stopping brain tumours coming back after surgery.

An experimental treatment that uses electric fields to disrupt and interfere with the division of cancer cells has been developed. It was used in the phase 3 EF-11 trial in the USA, Europe, and Israel. The device is battery powered and gives low-amplitude alternating electric fields through disposable electrodes stuck to the scalp. In the trial, 120 patients with glioblastoma that had come back used the electrical field device for about 20 hours each day. A similar number of patients had the standard chemotherapy for recurrent glioblastoma.

The trial seemed to show that the electrical field therapy may work as well as chemotherapy for glioblastoma that has come back after previous treatment. The researchers say that the electrical field therapy seems to be safe and the only side effects reported were skin irritation from the electrodes. We need more research into electric field treatment before we know how helpful it may be for brain tumours.

Cancer Research UK are funding a study which is following children who’ve had successful cancer treatment. They are looking at their health in the years following their cancer treatment to see how it has been affected. They are also monitoring their general quality of life, how they do in school, and whether or not they go on to have children of their own. It is important that we understand the long term effects of treatments so that we can improve them in years to come. If we can identify some of the risks, doctors may be able to take steps to prevent other health problems from developing.

Children who’ve been treated for other types of cancer in the past may have an increased risk of getting a brain or spinal cord tumour in the future. This type of study can help doctors to predict who is at risk. If they knew that, they may be able to take action to reduce the risk for these patients.

There is more about the potential effects of brain tumour treatment on children in this section of CancerHelp UK.