Brain Tumour Treatment – Therapies

Having a brain tumour is complex. Treating a brain tumour is complex. Increasingly, brain tumour treatment options are being ‘personalised’ to meet the needs of the patient.

Today, clinicians no longer treat just plain cancer; they use the knowledge of the biology of cancer to plan treatments more effectively, as they know so much more about it. The current options include surgery, radiation therapy, and chemotherapy (chemo). Having ‘chemo’ will probably conjure up an image of a terribly sick, bald person. There have been major improvements in chemotherapy so that most regimens are well tolerated. Many people have a combination of treatments and the choice of treatment depends mainly on the following:

  • The type and grade of brain tumour
  • Its location in the brain
  • Its size
  • Age
  • General health

Cancer therapy often damages healthy cells and tissues and therefore side effects are common. Before treatment starts, ask your oncologist about possible side effects and how treatment may change your normal activities.

These are things you may want to ask before you begin treatment:

  • What are my treatment choices? Are there any choices available elsewhere that aren’t available here?
  • Which do you recommend for me? Why? How does that treatment work?
  • What are the expected benefits of each kind of treatment?
  • What can I do to prepare for treatment?
  • Will I need to stay in the hospital? If so, for how long?
  • What are the risks and possible side effects of each treatment? How can side effects be managed?
  • How will treatment affect my normal activities? What is the chance that I will have to learn how to walk, speak, read, or write after treatment?
  • Would a research study (clinical trial) be appropriate for me? If it isn’t, why not?
  • I might decide to seek a second opinion. What would the questions be that you would ask?

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Chemotherapy

What is it?

A treatment which uses drugs to treat cancer cells. Sometimes more than one drug is used; this is called combination chemotherapy.

Chemotherapy works on cancer cells in three ways:

  1. It kills cancer cells
  2. It alters the cells damaging potential
  3. It ‘tees up’ the cancer cells for treatment with further drugs (also called pro-drug therapy).

Should I have chemotherapy?

Not a simple response. We said it was complex; each case has to be assessed individually. To help you decide, ask about the drug’s main side effects and trust in your healthcare team. Be guided by this.

The side effects of chemotherapy depend mainly on which drugs are given and how much. Common side effects include nausea and vomiting, loss of appetite, headache, fever and chills, and weakness. If the drugs lower the levels of healthy blood cells, you’re more likely to get infections, bruise or bleed easily, and feel very weak and tired. You will be checked for low levels of blood cells. Some side effects may be relieved with medicine.

Such is the progress in personalised treatments that neuropathologists can now identify which tumours are likely to respond to chemotherapy. Specific tests might provide information that can be used to influence your treatment and diagnosis. Not all hospitals run such tests but you can ask for them. These tests (also called molecular markers) can:

  • Aid the diagnosis of brain tumours which are sometimes hard to diagnose
  • Allow clinicians to work out a prognosis
  • Indicate whether a tumour will respond to a specific type of treatment

The downside of this is that you may discover that your tumour type might not respond to treatment, so if you ask the question, you need to be prepared that you might receive information you’d rather not know.

The MGMT methylation test detects a chemical change in the DNA that shows how the cells are able to fight certain chemotherapy drugs (i.e. repair the damage caused by the drug so that the cancer cells survive and continue to grow). Tumour samples can also be tested for a ‘1p/19q’ genetic change in the chromosomes that may provide information about the likely sensitivity to DNA acting drugs.

The MGMT and 1p/19q tests will only be relevant to some brain tumours. They can also only be done where a biopsy has been performed, and biopsy material can be obtained and analysed (it does not necessarily matter how long ago the biopsy was performed).

The MGMT methylation test is relevant to all anaplastic gliomas (WHO Grades III and IV).

1p /19q test is relevant to certain tumour types.

The tumour types for which these tests can be done are shown by a tick below.

Diagnosis      Grade MGMT 1p/19q
Anaplastic astrocytoma WHO grade III
Oligodendroglioma WHO grade II
Anaplastic Oligodendroglioma  WHO grade III
Oligoastrocytoma WHO grade II
Anaplastic Oligoastrocytoma WHO grade III
Glioblastoma WHO grade IV

How chemotherapy works

Chemotherapy directly attacks brain tumour cells and disrupts their growth. It is not used to treat all brain tumours and sometimes it is used to shrink a tumour or slow its growth; it won’t always get rid of a tumour. It is generally used to treat a malignant tumour. The blood brain barrier causes problems in the delivery of chemotherapy. The blood brain barrier is there to protect the brain from toxic substances so trying to deliver chemotherapy agents to the site is not easy.

How is chemotherapy given?

Usually in cycles. This gives the patient time for the healthy cells to recover in between treatments. The frequency and length of the treatments depends on the factors mentioned previously. Treatment – rest cycles are often repeated over several months.

What are the major, currently used chemotherapeutic agents?

Main agents used are Procarbazine, CCNU and Vincristine (known as PCV), temozolomide, carboplatin, and carmustine. Until recently, PCV was the mainstay of treatment and temozolomide has been a relatively recent addition. Avastin is the new kid on the block but the jury is still out as to whether this is an effective agent. Research (2003) has shown that it can cause increased tissue invasion. This treatment may be advised but only in combination with other therapies.

Agent What it is How administered Side effects
PCV: chemotherapy combination of more than one drug – procarbazine + CCNU (also called lomustine) + vincristine = PCV. Procarbazine and CCNU are oral medications and vincristine is given intravenously Orally and intravenously over a 28 day cycle Fatigue, nerve discomfort, jaw pain and ringing in your ears.
Temozolomide An alkylating agent that crosses the blood brain barrier and has been approved by NICE. It has shown promise for the long-term management of gliomas and may also be useful in medulloblastomas and metastatic tumours One to six capsules a few days a month for a year or more. Treatment-rest cycles can last for several months or years.

 

NB There is little or no difference between PCV and temozolomide apart from the way it is given.

Fatigue, nausea and constipation.
Carmustine A nitrosourea agent which disrupts the DNA of tumour cells to stop them from proliferating. Intravenously or by biodegradable implants (wafers), which are inserted into the cavity left once the brain tumour has been removed. The agent is then released directly into the tumour. The wafers dissolve over the next two to three weeks. If administered intravenously, you will be an outpatient and the cycle usually repeats every 6 weeks.

 

The disadvantage with Carmustine wafers is that the agent does not reach invading cells but remains local.

Wafers may cause seizures, cerebral oedema and problems with wound healing. Side effects include fatigue, nausea and constipation.
Avastin: also called bevacizumab Anti-angiogenic therapy: it inhibits the growth of blood vessels which feed tumour Intravenously. You cannot have Avastin if you are having surgery. This has not been approved by NICE and therefore may not be funded by your commissioning board. Headache, confusion, vision problems, feeling light-headed, fainting, and seizure

New drugs are being developed and researched. These tend to fall into several camps and would, with luck, be in a clinical trial:

  • Agents that stop cell division
  • Anti-angiogenic therapy: these drugs inhibit the growth of blood vessels which feed tumour;
  • Differentiating agents: these drugs act on the cancer cells to make them mature into normal cells. They work in three ways:
    • They slow down malignancy
    • They limit the number of cells dividing
    • They sensitise the cells to existing therapies
  • Immunotherapy: a seek and destroy mission. These drugs offer a unique method of treatment, and are often considered to be separate from chemotherapy. Compared with other forms of cancer treatment such as surgery, radiation therapy, or chemotherapy, immunotherapy is still fairly new. There are different types of immunotherapy. Active immunotherapies stimulate the body’s own immune system to fight the disease. Passive immunotherapies do not rely on the body to attack the disease; instead, they use immune system components (such as antibodies) created outside the body. Immunotherapeutic agents include interferons, natural proteins that are toxic to cancerous cells and specific antibodies. This treatment can improve the immune system’s ability to locate and destroy tumour cells.
  • Gene therapy: the transfer of genetic material to a tumour cell to destroy the cell or to change the nature of malignant cells so that they become more sensitive to therapy (pro-drug treatment).
  • Targeted molecular therapies: these agents block a specific growth pathway which a tumour cell may use (e.g. tk inhibitors).
  • Intratumoural therapies: this involves inserting new biological therapies directly into the tumour.

How are these agents taken?

  • Most commonly by mouth (orally) – some chemotherapy drugs are given in pill or capsule form.
  • Injection into a vein (intravenously) – you shouldn’t need to be admitted into hospital for this.
  • Injection into an artery (intra-arterially) – not common. This method has fallen out of favour as it has been associated with greater toxicity to the brain.

Click here to see a clever little video about chemotherapy for brain tumours. It covers chemotherapy, steroid therapy and anti convulsant medication and lasts about 12 minutes. It is Australian, so don’t call the helpline in Australia – call brainstrust!

http://www.cancercouncil.com.au/50913/get-informed/about/about-cancer/understanding-brain-cancer-support-videos/?pp=50913

Chemobrain

Common sense would tell you that any drugs delivered to the brain must be harmful. Cancer survivors struggling with the long-term effects from their treatments cannot help but wonder if there is a cure for the cure.

This is a new area of research. After chemotherapy hair grows back, fatigue abates but a spaced out feeling lingers – impaired memory and an inability to concentrate or multitask dogs some patients. It is suggested that that the cause lies deep within the brain, in regions where immature and newborn cells (progenitor cells) are proliferating. These self-renewing cells, part of the complex structures needed for memory and other normal functions, are particularly vulnerable to toxic chemotherapy drugs. On the other hand the very stress of a brain tumour diagnosis or depression may also contribute to memory loss, so it is hard to say whether chemobrain exists or is exaggerated, and if it is, whether it is prolonged and progressive.

(Adapted from The Cloud of Chemotherapy, Ellen Clegg, The Boston Globe, 5 April 2009).

A NICE word

The National Institute for Health and Clinical Excellence (NICE) is an independent body set up by the Government to assess medicines and treatments. It gives guidance to the NHS about how drugs should be used.

For a bit more information have a look at this little video, which lasts about 12 minutes. It covers temozolomide, side effects of chemo and how to manage them, steroids, and anticonvulsant medication.

http://www.cancercouncil.com.au/50913/get-informed/about/about-cancer/understanding-brain-cancer-support-videos/?pp=50913

The website you have prepared is impressive and very helpful to many of those struggling with their diagnosis and treatment.

Professor Roy Rampling, Glasgow June 2011

For more information about referrals, and to find out more then why not call our 24/7 helpline on 01983 292405 or email helen@brainstrust.org.uk

Download the brain tumour radiotherapy book to understand this brain tumour treatment

Radiotherapy

What is it?

Radiation therapy kills brain tumour cells with high-energy x-rays, gamma rays, or protons. It usually follows surgery. The radiation kills brain tumour cells that may remain in the area, following surgery. Sometimes, people who can’t have surgery have radiation therapy instead. It may also be given in combination with chemotherapy. Radiotherapy is used in 50% of all cancer patients.

Should I have radiotherapy?

Even if the tumour has been removed, radiotherapy can be recommended to keep hidden cells from growing. This should destroy left over cells and prevent a recurrence of growth.  There is a suggestion that, several years after radiotherapy treatment, another brain tumour could develop because of this treatment. There is also a risk of radiation necrosis. This is rare. But you should take all factors into consideration. Again, talk with your doctors, trust them and be guided by them. You should not have radiotherapy if you only have a few dividing cells in your cancer. The therapy would not be very successful.

How does radiotherapy work?

Radiation treatments take advantage of the fact that healthy tissue repairs damage in about 8 hours, so that regular low to moderate doses of radiation can be delivered daily.  Diseased tissue cannot repair like this, so eventually the tumour cells die as they cannot reproduce effectively. Tumour cells may still show up but they may have lost the power to divide.

The amount delivered to the brain is limited by how much radiation normal tissue can tolerate. Limits are well researched.

Radiation is measured in units called Gray (Gy) or centigray (cGy). The amount of overall dose and amount to be given each day will depend on the tumour type.

How is radiation therapy given?

Little and often! Usually treatment is scheduled Monday to Friday so you will need to pitch up at the hospital every day, with weekends off. Dates and times are usually given in advance and sometimes you can work with the planning team to fit in around your commitments. However, before you get to your first dose there is a significant amount of preparation to be done. This can take a month, but if you have had surgery you will need this time to recover and gather your strength for this treatment. Due to the ‘plastic’ nature of the brain your brain also needs time to recover.

By now you will have met your radiation oncologist. They will discuss your case each week in the MDT meetings. You will need to go to some planning sessions so that all the measurements can be taken. These are called simulations, when the mapping is done to figure out how best to arrange the radiation beams and how best to protect the healthy tissue. If you are having radiotherapy, the chances are that you will need to wear a transparent Perspex mask, made bespoke for you, which is clamped to the table to hold your head in place whilst you are receiving the treatment.

To be honest, having the mask made was worse than the actual treatment for me. The very worse bit? It lasted about one minute. I couldn’t see, I couldn’t move and I couldn’t speak. The straps were being ‘welded’ onto the mask by my ears and it was very hot, burning my ears. I had to wiggle my hands to let the nurse know that something was wrong. After this the whole thing was a breeze.

Helen, Southampton, 2012

The mask will enable you to breathe and see normally but it can feel claustrophobic. You will only need to wear it for a few minutes at a time. If you are having whole brain radiotherapy (for secondary brain tumours) you will not need a mask.

Before each session of radiation treatment, you may be asked to put in a mouth guard to protect your gums. Then you will be positioned carefully on a table and the mask fitted. You will then be left alone in the room whilst the kit moves around you, zapping away. It is not in the least painful but you will need to keep still. You may be able to talk to the radiographer who will keep a close eye on you from the next room.

What are the different types of radiation treatment?

Doctors use external and internal types of radiation therapy to treat brain tumours.

External beam radiation therapy

Fractionated external beam radiation therapy (EBRT) is the most common method of radiation therapy used for people with brain tumours.  A large machine outside the body aims beams of radiation at the head. Because cancer cells may invade normal tissue around a tumour, the radiation may be aimed at the tumour and nearby brain tissue, or at the entire brain. Some people will also need radiation aimed at the spinal cord.

You will lie on a treatment table in a fixed position. Powerful and precisely placed radiation beams are directed at the tumour using a sophisticated device called a medical linear accelerator (linac). This rotates around you, delivering beams from different angles. When these beams converge on your tumour, the effect is very powerful.

The following details some recent advances in types of radiotherapy. Not all of these are yet standard practice in the UK:

Intensity-modulated radiation therapy (IMRT)

Similar to 3DCRT and is appropriate for both benign and malignant tumours. IMRT uses radiation blocking to sculpt the shape of a ‘dose’ around sensitive structures e.g. the optic nerve. Clinicians can precisely shape the radiation beam so that it conforms to the 3D shape of the targeted tumour. Dose is varied to deliver higher, more effective doses to the tumour, which creates a ‘hot spot’ at the tumour site. It is like 3 to 4 torchlight beams being shone from different directions but at one spot. The light is most intense where the beams meet. But on its own, each beam is relatively weak and passes through normal tissue without much effect. It takes a bit longer to deliver because of the complexity, so about 15 to 45 minutes per treatment. The problem with IMRT is that, with the best will in the world, you move as you breathe. So the very tight margins used by IMRT makes these movements, however slight, a very real problem. This is addressed by using image guided radiotherapy.

Image guided radiotherapy (IGRT)

Prior to the introduction of IMRT, radiation oncologists had to contend with variations in patient positioning, internal movement, and respiratory movement. They do this by treating a wider margin of the tumour. So, for example, to treat a golf ball sized tumour, they would use a tennis ball. With IGRT you can use a golf ball to treat a golf ball.

IGRT gives high resolution, 3D images to pinpoint the tumour site, adjusting your position as necessary, and complete a treatment – all within the time slot.

Proton beam radiation therapy

The source of radiation is protons rather than x-rays. This is a type of particle therapy which uses a beam of protons to irradiate the tumour. The doctor aims the proton beam at the tumour. The dose of radiation to normal tissue from a proton beam is less than the dose from an x-ray beam. All protons of a given energy have a certain range; no proton penetrates beyond that distance, so this treatment is good in cases where there is a need for the radiation dose to fall off to zero after it hits the target. In conformal therapy there is exit radiation beyond the tumour, which is why you lose your hair on the side where the beam leaves your head, but proton beams slow down and stop within the target. Proton beam therapy is incredibly expensive. At the moment there are two proton beam machines in the UK but these can only be used for eye cancer. People who need this treatment have to go the USA. The treatment is delivered as conformal therapy and as radiosurgery.

Internal radiation therapy (implant radiation therapy or brachytherapy):

Internal radiation isn’t commonly used for treating brain tumours and is under study. The radiation comes from radioactive material usually contained in very small implants called seeds. The seeds are placed inside the brain and give off radiation for months. They don’t need to be removed once the radiation is gone.

Side effects and useful pointers:

During your treatment, you should only use fragance free and mild soap. So nothing on your hair like gel, or colouring.  E45 cream is an excellent moisturizer to use on your skin, which will become burnt.

You will probably not feel any side effects for at least two weeks. Then the following starts to happen:

Hair loss – this is gradual. It thins and then becomes patchy, usually where the beam leaves your head. Apart from affecting appearance, it makes you notice change in temperatures. It will grow back; it might have a different texture but you won’t be bald forever.

Thrush – if the beam is near your mouth you may find that it becomes sore. Tell your nurse, who can provide things to alleviate this.

Nausea – you may be sick or feel sick, particularly if the beam is catching your ear. Again, don’t suffer in silence. Anti-sickness medication will bring relief.

Skin irritation – your scalp may become red, dry and tender. Apply moisturizers after your treatment; not before. Your health care team can suggest ways to relieve these problems.

Ear congestion – if the beam is passing through your ear, this will become dry and then irritated towards the end and beyond your treatment. You may find that your ear is ‘leaking’. Again, see your doctor who will provide ear drops.

Fatigue – it is important to stay active. Some people continue to work. However, you must rest when you need to.

People warned me that 4 to 6 weeks AFTER the treatment has finished I would feel really tired. This lasted about a month; having a shower was a supreme effort and I had to lie down afterwards. A course of radiotherapy is the equivalent as having another round of major surgery. Listen to your body.

Helen, Southampton, 2012

Brain swelling – sometimes, but not often, radiation therapy causes brain tissue to swell. You may get a headache or feel pressure. Your health care team will watch for signs of this problem. They can provide medicine to reduce the discomfort. Radiation sometimes kills healthy brain tissue. Although rare, this side effect can cause headaches, nausea, seizures, or very rarely, death. Call your doctor immediately if you experience any symptoms which are new or different.

Weight loss – you will lose weight. This is probably the only time when you will be told it is Ok to eat foods which are high in fat. Eat a little and often. Some patients find that Guinness is excellent – good for hair and cell renewal.

Want a little more visual information? Have a watch of this 12 minute video. It covers ‘What is radiotherapy?’, types of radiotherapy, side effects and how to manage these:

http://www.cancercouncil.com.au/50913/get-informed/about/about-cancer/understanding-brain-cancer-support-videos/?pp=50913

Immunotherapy

Immunotherapy is often hitting the headlines, promising that it could give treatments the precision needed to be more effective in treating cancer, not just brain cancer but many other cancers too.

What does this mean for brain cancer?

Immunotherapy as a cancer treatment has waxed and waned since 1900. Current immunotherapies for brain cancer fall into six broad categories: cancer vaccines, checkpoint inhibitors, oncolytic virus therapy, adoptive cell therapy, adjuvant immunotherapies, and monoclonal antibodies. So there is much activity around this as a potential treatment. However, there are always caveats when there is a big media noise around ‘game changing’ treatments for cancer. Brain cancer is particularly challenging to treat due to the blood brain barrier (which is there to stop toxins getting into the brain) and there are so many different types of brain tumour. At the moment we know that there are even 6 subsets of a glioblastoma brain tumour. It can work BUT it is hugely expensive as each treatment is personalised to each individual. And of course, not each individual will be responsive to the treatment, which can also be highly toxic. It is thought that if, at some point in the future, immunotherapy could be a potential treatment for brain cancer then it would probably only work in 10% of patients. And it comes with significant risk. When it goes wrong, it can go horribly wrong.

So what is the current state of play?

There are some trials but mostly these are phase 1 (so very early trials) and mostly in the USA so it is very expensive. And it isn’t just the finance. Sometimes the window for accessing these treatments is very tight and has to be before any other treatment. So timing is key. And even if these kinds of hurdles are overcome then the vaccine may not always be available. Best thing to do is to ask your clinical team about immunotherapy and clinical trials.

Click here for a list of current open UK trials

And if you want more information about other trials from abroad then email hello@brainstrust.org.uk

So yes, this is promising for some brain cancer patients but we are a long way off seeing any real progress. This is not going to be a quick win, nor should it be. It is more important that it is right, than quick.

Technology

Tumour treating fields: OPTUNE

What is it?

http://www.optune.com/

Optune is a physical therapy. It is a portable, non-invasive medical device designed for continuous use by patients. Unlike healthy cells, cancer cells divide quickly, in an uncontrolled way (mitosis). As they divide, they form a mass or tumour. Optune is a non-invasive regional therapy that targets dividing cancer cells in the brain and generally does not harm healthy cells. It works by creating alternating, “wave-like” electric fields called Tumour Treating Fields (TTFields). TTFields travel across the upper part of the brain in different directions to help slow or stop recurrent glioblastoma cancer cells from dividing.

Optune is delivered through 4 transducer arrays that are placed directly on the scalp to target the tumour. The transducer array placement is determined based on each patient’s MRI results to maximize the therapy’s effect on the tumour.

Optune has received marketing approval in the U.S. under the brand name Optune™ for recurrent GBM. The NovoTTF-100A System is a CE Marked device cleared for sale in the European Union, Switzerland, Australia and Israel.

How is it used?

Studies have shown that treatment is more effective if used for more than 18 hours a day. It is worn from first diagnosis until death and is used with the standard treatment protocol of radiotherapy and chemotherapy (temozolomide).

To work effectively, the transducer arrays must be placed directly on the scalp, so the head has to be shaved throughout treatment. The transducer arrays need to be replaced one to two times per week (every 4 to 7 days), depending on factors like how much the patient sweats and how quickly hair grows. Patients can shower without taking off the transducer arrays but they have to wear a shower cap.

The patient must learn to change and recharge depleted device batteries and to connect to an external power supply overnight. In addition, the transducer arrays need to be replaced once to twice a week and the scalp re-shaved in order to maintain optimal contact. Patients carry the device in an over-the-shoulder bag or backpack and receive continuous treatment without changing their daily routine. This is heavy – about 7kgs. Second generation systems weigh much less (1.3kgs)

Optune commonly causes skin irritation beneath the transducer arrays and in rare cases can lead to headaches, falls, fatigue, muscle twitching or skin ulcers. 45% of patients had skin irritation (2% severe).

Clinical trial

http://www.optune.com/HCP/clinical-data.aspx

http://www.optune.com/Content/pdfs/Optune_IFU_8.5×11.pdf

A randomized phase III trial was conducted in newly diagnosed patients. The primary endpoint was progression free survival (PFS). The pre-specified, interim analysis of EF-14 trial data was conducted on the first 315 patients, representing approximately 50 percent of the targeted study population. The trial was stopped early due to the success.

The data shows that:

  • Patients treated with TTFields together with temozolomide demonstrated a significant increase in progression free survival compared to temozolomide alone (median PFS of 7.1 months compared to 4.0 months, hazard ratio=0.63, p=0.001).
  • Patients treated with TTFields together with temozolomide demonstrated a significant increase in overall survival compared to temozolomide alone (median OS of 19.6 months compared to 16.6 months, hazard ratio=0.75, p=0.034).
  • The percentage of patients alive at 2 years in the TTFields together with temozolomide arm was 43% compared to 29% in the temozolomide alone arm.

In summary you are looking at an average of an extra 12 weeks for both PFS and OS).

“These results are spectacular – a lot better and much more convincing than we ever would have dreamt of,” said Dr. Roger Stupp, M.D., Director of the University Hospital Cancer Center at the University of Zurich, Zurich, Switzerland and EF-14 Principal Investigator. “A new standard of care for patients suffering from glioblastoma is born.”

Exclusion Criteria

  1. Actively participating in another clinical treatment trial
  2. Within 4 weeks from surgery for recurrence
  3. Within 4 weeks from any prior chemotherapy
  4. Within 4 weeks from radiation therapy
  5. Pregnant
  6. Significant co-morbidities within 4 weeks prior to enrollment
  7. Implanted pacemaker, defibrillator or deep brain stimulator, or documented clinically significant arrhythmias
  8. Infra-tentorial tumor
  9. Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced

1) Significant liver function impairment—AST or ALT > 3 times the upper limit of normal

2) Total bilirubin > upper limit of normal

3) Significant renal impairment (serum creatinine > 1.7 mg/dL)

4) Coagulopathy (as evidenced by PT or APTT >1.5 times control in subjects not undergoing anticoagulation)

5) Thrombocytopenia (platelet count < 100 x 103/μL)

6) Neutropenia (absolute neutrophil count < 1 x 103/μL)

7) Anemia (Hb < 10 g/L)

8) Severe acute infection

Approved Indication

The U.S. FDA has approved Optune for use as a treatment for adult patients (22 years of age or older) with histologically-confirmed GBM, following histologically – or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy. The device is intended to be used as monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Benefits and risks

Benefits

  • Optune works as well as chemotherapy.
  • There are minimal side effects. Optune delivers treatment to the region where the tumor is located and does not cause many of the side effects of chemotherapy, including infections, nausea, vomiting, diarrhoea, and blood toxicities.
  • Better quality of life. Patients using Optune reported a better quality of life with improved cognitive and emotional functioning compared to patients treated with chemotherapy.

Risks

Skin irritation is often seen under the transducer arrays when using Optune. The irritation can be treated with steroid cream or by moving the transducer arrays. If it isn’t treated, the skin irritation could become more serious. This may lead to open sores, infections, pain and blisters.

Headaches, weakness, convulsions, and thinking changes were seen in the clinical study of Optune. In the device group. 18 out of 116 patients had headaches, 10 out of 116 patients had weakness, 10 out of 116 patients had convulsions, and 6 out of 116 patients had thinking changes. These events are also seen in patients with recurrent GBM who do not use Optune. However, there was a higher rate of these problems overall in Optune patients (43.1%) compared to patients on cancer drugs (36.3%). Only skin redness and open sores are related to Optune treatment itself.

Comments

It seems to only be effective on patients with smaller GBMs in the supratentorial region.

It appears to provide an extra 12 weeks PFS and OS.

It costs $20,000 per month.

The clinical community is skeptical of this treatment.

Tumor Treating Fields (TTF-Optune)

Unexpected results – only phase 3 trial that has met primary end points. Overall survival extended by about 12 – 16 weeks.

Not adopted widely because:

  • lack of experience
  • science is not explained
  • interim data set is not representative
  • patients don’t all accept the device
  • cost (£20k per month)
  • shift needed from molecular physics to biophysics
  • Impractical, unwieldy and unsightly

There is a huge marketing machine behind Novocure. They said if this had been a drug it would have been accepted. What has thrown them is that Roger Stupp was the principle investigator who sat on the independent panel. He is very highly regarded and was behind the current standard protocol.

It will be very many years before this is approved by NICE for use in England. In the meantime patients will need to source and finance this for themselves.

Questions you should ask yourself:

How would I feel having to wear this round the clock for the rest of my life?

How will I feel having to shave my head twice a week?

How will I feel having to carry a 7KG battery around all of the time?

This will mark me as different when I’m are out and about. How do I feel about this?

What is important to me? e.g. some people may have a reason for wanting the extra time. For others their identity may be more important.

How will I fund this treatment?

Radiosurgery

What is Radiosurgery?

Radiosurgery is a medical procedure used for brain tumour treatment, as well as treatment for other forms of cancer. It uses non-invasive, highly precise radiation beams, usually in one single session, to destroy painlessly or shrink tumours that could otherwise be inaccessible for open surgery.

It is also known as stereotactic radiosurgery (SRS) when used to target brain tumours.

Radiosurgery is effective on discrete, well encapsulated and quite small brain tumours (less then 3 to 4 cm in diameter). Super skinny beams of x-rays or gamma rays are directed at the tumour from different angles. For this procedure, you wear a rigid head frame. The therapy may be given during a single visit (stereotactic radiosurgery) or over several visits. You may also hear these being referred to as Gamma Knife and Cyberknife. These are the commercial names, like Hoover is for vacuum cleaners.

There are some differences between the two. The Cyberknife is a low energy linear accelerator and does not require you to be placed in a frame fixed to the skull. It is frameless SRS. The Gamma Knife is good for particularly small targets and is given after a radiation source helmet is placed on your head. There is also Novalis Tx Radiosurgery.

These all offer a similar (but not identical) minimally invasive approach to brain tumour treatment, and are available privately and through the NHS.

Don’t be misled by the words surgery and knife. There is no invasive surgery, so no knife. In this type of treatment though the beams converge on a single point – the tumour. There is no margin added.

In addition to cancer, radiosurgery is also shown to be beneficial for the treatment of non-cancerous conditions, including disorders such as arteriovenous malformations (AVMs) which are an abnormal connection between veins and arteries that can be dangerous when occurring in the brain. Radiosurgery is an established medical procedure and was first developed in 1951.

What is the difference between radiosurgery and radiotherapy?

Radiotherapy also uses non-invasive radiation beams to treat cancer cells and shrink tumours. But unlike radiosurgery, radiotherapy is normally given as a series of short, daily treatments called fractions and not a single session with a higher dose of radiation. How many fractions or daily treatments will depend on the tumour type and fitness of the patient.

How does radiosurgery and radiotherapy treat cancer?

Radiosurgery and radiotherapy use high-energy radiation beams to deliver the prescribed radiation dose directly to tumour cells, causing them to shrink or die. Treatment results, which are visible on follow-up scans, include shrinkage of the tumour or no further tumour growth. Because cell destruction is a lengthy process, it can often take up to six months before the effect of treatment can be determined by doctors.

What type of patient can radiosurgery benefit?

Due to its power and accuracy radiosurgery can give clinicians the ability to treat patients with cancers once considered untreatable and those for whom surgery is not an option, such as tumours deep in the brain.

Of the 120+ different types of brain tumour that people can contract, you are most likely to have radiosurgery if you have an acoustic neuroma that is less than 3cm across. Radiosurgery can also be used for other brain tumours, including small secondary brain tumours, small pituitary adenomas and for people who can’t have brain surgery due to other medical conditions. It is also used for Haemangioblastomas that couldn’t be removed, were only partially removed, or came back after surgery.

Specialists don’t recommend radiosurgery for larger brain tumours. It isn’t possible to get the same dose of radiotherapy throughout the treatment area with a large brain tumour.

Radiosurgery may also not be suitable if there are certain nerves running through the treatment area. The nerves could be given too much radiation. This could cause problems such as hearing loss, depending on the role of the affected nerves.

Accessing radiosurgery

For more information about referrals, and to find out more then why not call our 24/7 helpline on 01983 292405 or email helen@brainstrust.org.uk

Resources used

Patient/carer representative

Professor of Cellular and Molecular Neuro-Oncology

National Institute for Health and Clinical Excellence guidelines – Improving Outcomes Guidance Brain and CNS Tumours 2008

Living with a Brain Tumour (Peter Black) 2006

Fast Facts – Brain Tumors (Abrey and Mason) 2009

NCRI Clinical and Translational Radiotherapy Clinical Studies Group (CTRAD)

http://www.cancercouncil.com.au/

Navigating Life with a Brain Tumour, L. Taylor, F. Alyx B. Umphrey, D. Richard (2013)

Benign Brain Tumour, NHS Choices (2013), available at: http://www.nhs.uk/conditions/Brain-tumour/Pages/Introduction.aspx

Malignant Brain Tumour, NHS Choices (2013), available at: http://www.nhs.uk/Conditions/brain-tumour-malignant/Pages/Introduction.aspx

Date published: 17-05-2009
Last edited: 28-02-2018
Due for review: 28-02-2021