Treatment of Malignant Brain Tumours in Children

What is the most effective treatment in treating malignant brain tumours in children?

I have looked into various treatments for malignant brain tumours in children, however, in order to determine which treatment is the most effective; I have explored other factors regarding this. I will outline what a brain tumour is, the main types of malignant brain tumours in children, risk factors and causes as well as symptoms. I will look at how brain tumours are detected and diagnosed before illustrating the main treatments and their side effects. I will further look at relatively new treatments for brain tumours in children as well as latest research before coming to a conclusion.

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A brain tumour is a group of cells that grow unusually in the brain and can either be malignant or benign. Malignant brain tumours are cancerous whilst benign brain tumours are non – cancerous. Brain tumours are the second most common tumours in children and they develop from stem cells that support the nerve cells of the brain. These cells are known as glial cells and a group of glial cells is known as a glioma. They are named after the area they are growing in, for example; “a tumour of the pituitary gland is called a pituitary adenoma and a tumour developed from the covering of the brain (the meninges) is called a meningioma”[1]. Brain tumours can either be primary or secondary, also known as metastatic. Primary brain tumours are tumours that originate in the brain whereas secondary brain tumours are tumours that grow in another part of the body and spread to the brain through the bloodstream. “Cancer of the lung, breast, kidney, and stomach and melanoma skin cancer can all spread to the brain and they usually spread to the cerebral hemispheres or to the cerebellum of the brain (hindbrain) which is involved in balance and the timing and coordination of skilled movement”[2]. Brain tumours can start anywhere in the brain and can affect various processes, for example, a tumour in the parietal lobe (involved with touch, pressure, pain) can affect speech, reading or writing, a tumour in the occipital lobe (involved with sight) can cause sight problems and a tumour in the cerebellum can affect balance and movement. Malignant brain tumours, also known as “high grade” brain tumours (grade 3/4) are life threatening and fast growing and can spread to other parts of the brain or to the spinal cord. Benign tumours are classed as “low grade” brain tumours and do not spread to other parts of the body or the brain, however they can sometimes be life threatening. Some benign tumours can develop into a malignant tumour and this is known as “malignant transformation or progression to malignancy”[3].

There are many different types of brain tumours, however I will focus the most common types of malignant brain tumours in children; gliomas and embryonal tumours. Around half of all childhood brain tumours are a type of glioma; a group of tumours that start in glial cells in the brain. The main type of glioma is astrocytoma and they make up 43% of all brain tumours in children. Astrocytomas are tumours that start in cells called astrocytes; glial cells that help and support nerve cells[4]. Low grade astrocytomas are slow growing and are the most common type in children, making up 73%. These include pilocytic astrocytomas which are slow growing grade 1 tumours and optic gliomas which are astrocytomas that start in the optic nerves and are often linked with an inherited condition called neurofibromatosis. Diffuse astrocytomas are grade 2 tumours that can grow into nearby tissues, making them difficult to remove with surgery; they account for 10-15% of childhood brain tumours in the UK. High grade astrocytomas include grade 3 anaplastic astrocytomas and grade 4 glioblastomas which are the fastest growing astrocytoma. Another type of glioma includes grade 2 oligodendrogliomas which start in oligodendrocytes in the brain (glial cells that make fatty acid substance for electric signals by nerve cells) and account for 1% of brain tumours in children. Ependymomas are another type of glioma; they are tumours that start in the ependymal cells that line the ventricles of the brain. They range from grade 1 to grade 3 and are the third most common type of brain tumour in children, accounting for 5-10%. Astrocytomas and oligodendrogliomas can become aggressive over time and can grow into normal brain tissue whilst ependymomas do not[5].

“About 20-25% of childhood brain tumours are embryonal tumours. Previously known as primitive neuroectodermal tumours (PNETs), they are high grade tumours and occur mostly in younger children with more than half of embryonal tumours being diagnosed in children under 10 years old. Embryonal tumours develop from cells that are left over from the earliest stages of our development while we are still growing in our mother’s womb as an embryo”[6]. The most common type of embryonal tumours are medulloblastomas which account for 73%. They are the most common type of high grade tumours in children, making up around 20% of childhood brain tumours and they are more common in boys than girls. Medulloblastomas are most commonly found in the cerebellum of the brain, a part of the posterior fossa that controls coordination and balance. They sometimes spread to other parts of the brain or spinal cord, through the cerebrospinal fluid (CSF) that surrounds the brain. Medulloblastomas are most commonly diagnosed around the age of 5[7].

Although the direct causes are not currently known, there are certain factors which may increase a person’s risk of developing a brain tumour. Dr Poolo (a doctor at my local GP) explained that there are three main factor types which affect the occurrence of brain tumours in children. These factors include genetic factors which are passed down from parents to offspring, congenital factors which are present at birth and acquired factors; obtained from the environment. Following further research, I discovered that about 5% of brain tumours are linked to hereditary genetic conditions which include Li-Fraumeni syndrome, tuberous sclerosis, turcot syndrome and Von Hippel-Lindal syndrome; in each one, “individuals inherit a germline mutation in a tumour suppressor gene which will lead to uncontrolled growth and accumulation of mutant cells”[8], forming a tumour. Some brain tumours can be present at birth and also be as a result of hereditary genetic disorders such a neuro-fibromatosis which causes tumours to form on nerve tissues particularly in the brain. Majority of brain tumours, however, are as a result of environmental factors and hazards. Exposure to radiation is one of the main risk factors, however it only accounts for a very small number of brain tumours. People who have had radiotherapy, CT scans or x-rays on their head have a higher risk of acquiring brain tumours such as meningiomas and malignant gliomas. This is because there is high energy radiation present which can affect cells and mutate DNA. People who have had cancer as a child, leukaemia or the chemotherapy drug methotrexate also have a higher risk of brain tumours. Other factors which can increase the risk of acquiring brain tumours include age, HIV/AIDS, smoking, being overweight or obese and living near a nuclear power plant, however there is little evidence for this[9].

An interesting resource I found showed the link between cell phone use/radiation exposure and a possible increased risk of brain tumours. Cell phone use may increase the risk of cancer, “but the evidence so far is inconclusive due to the relatively short period of time cell phones have been around”[10]. Cell phones emit radio waves which are a type of non-ionizing radiation from their antennas. When the phone antenna is placed close to the head, the nearby tissues are heated by the radiation and tumours may arise, however, “it is impossible to conclude what the long-term health effects of exposure could be”[11].

Brain tumours are quite rare and the symptoms a child shows may not always be associated with them. Symptoms and signs of brain tumours will vary depending on the site or size of the tumour; if the tumour is low grade, the symptoms come on much more slowly. Many symptoms are caused by a rise in pressure in the brain[12]. The most common brain tumour symptoms in children include; persistent vomiting or feelings of nausea over a two week period, recurring headaches over a four week period, (particularly when waking up), abnormal eye movements, fits or seizures, behaviour change, abnormal balance, walking and/or coordination, blurred or double vision, abnormal head position such as head tilt and delayed or arrested puberty[13]. Babies may have poor growth and irritability. If a child has one or more symptoms, they are taken to see a GP. At my local GP, the doctor stated that they are required to ask about the severity and duration of a child’s symptoms, and if they suspect that the symptoms are related to a brain tumour, they refer the child to a specialist such as a neurologist. If the neurologist suspects that the child has a brain tumour, they are referred to a paediatrician for further examination.
During the neurological examination, the specialist will ask questions about the patient’s health, carry out a physical examination and test the patient’s nervous system by looking at their vision, hearing, alertness, muscle strength, coordination and reflexes. They may also look at the back of the patient’s eyes to see if there is any swelling of the optic disc as this could be a sign of a brain tumour. An MRI scan or CT scan is then further carried out to establish the size, type and presence of the brain tumour. Patients who have seizures as their first symptom are seen as an emergency and are given a scan as their first test then afterwards, referred to a neuro-oncology multi-disciplinary team before consultation with a neurologist or neurosurgeon. If a tumour is found after the scan, a body scan may be carried out to determine if the tumour is primary or secondary. During a CT (Computerised Tomography) scan, CT scanners use x-rays to build up a 3D image of inside the head by taking many pictures of 2D slices through the child’s head and stacking them together using a computer. During an MRI (Magnetic Resonance Imaging) scan, magnetic fields are used to build up a 3D image of the brain by taking pictures from several angles around the child’s head to build a detailed picture. Before a scan is carried out, the child may be given a fluid injection called a contrast medium to give a more detailed image of the brain[14].

After the scan, if the tumour is a primary tumour and is in an area of the brain which can be operated on, a biopsy may be taken. This is when a sample of cells are removed and examined closely under a microscope in the laboratory to help diagnose the type and grade of the tumour. A resection may also be carried out which involves the surgical removal of the whole tumour. Debulking is when only part of the tumour can be removed, making it easier to treat the remaining tumour. Following biopsy or surgery, cells from the tumour will be analysed in a laboratory by a neuropathologist who will examine the cells and look for any possible patterns that are characteristics of the different types and grades of brain tumours. Accurate diagnosis is important and enables the medical team to give information about how the tumour could behave in future and also to recommend treatment options. Biomarker testing can also be carried out by doctors to look for markers or changes in certain genes in the tumour cells that may predict the speed at which the tumour will grow and indicate how well patients respond to certain treatments[15].

There are 3 main treatments for treating malignant brain tumours in children and I plan to discuss all three treatments with reasonable detail as well as the treatments used to relive symptoms. Before a child is treated, the multidisciplinary team; a group of different doctors, work together to create an overall treatment plan for the child. Treatment depends on several factors which include the size, type and grade of the tumour, its location in the brain, whether it has spread, possible side effects and the patient’s preference. A child may have one treatment or a combination of treatments.

Neurosurgery

Surgery or neurosurgery is the removal of the tumour as well as some surrounding healthy tissue during an operation. It is usually the first treatment used for a brain tumour and is often the only treatment needed to remove a low grade brain tumour. Removing the tumour helps to improve neurological symptoms, provide tissue for diagnosis and improve prognosis; the doctor’s prediction of the expected outcome of a disease. During surgery, a bone flap is removed from the child’s skull in a process known as craniotomy. During this process, the child is given an anaesthetic to make them fall asleep so they will experience no pain. A small area of their head will be shaved and a local anaesthetic may be used on the scalp. An incision will be made in the scalp and a small part of the child’s bone flap will be removed to allow most of the tumour to be safely removed. The bone flap is then replaced and the wound is closed using stitches or metal clips. The child is not allowed to eat anything before surgery and may be given steroids to help with any swelling after surgery. Total resection involves the whole tumour being removed; however, this is not always safe or possible to carry out and it depends on the child’s type of tumour and location in the brain. Alternatively, as much of the tumour will be removed safely and this is referred to partial resection or debulking[16]. Nevertheless, not all brain tumours can be operated on such as tumours near to the sensitive brain stem which controls breathing or slow-growing tumours that cause minor symptoms; removing the tumour may cause more harm than not operating. In this case, the child is “actively monitored”; closely monitored with appointments and scans until symptoms develop or worsen[17].

Awake craniotomy may also be used and this involves the patient being awake and alert during the above operation. The patient may experience relatively little pain so this may be unethical for children. Cortical mapping is used and this involves stimulating the brain with a tiny electrical probe. If a motor region of the brain is stimulated, it may cause twitching of a limb or the face[18]. This enables the surgeon to avoid important regions of the brain and stop the operation is anything changes, hence why the patient needs to be awake and alert. Operations are usually quite long and can often take more than 6 to 8 hours.

Sometimes the cerebro-spinal fluid does not flow freely and causes a build-up in the brain due to the tumour blocking its blood flow around the brain; this causes a rise in pressure in the skull and leads to headaches. To reduce the pressure, neurosurgeons insert a tube called a shunt into the child’s skull to drain some of the excess fluid away. The shunt has valves to make sure that it takes the fluid away in the correct direction; “away from the brain and towards other parts of the body that can easily absorb it such as the stomach lining”[19]. After the operation, the child may spend some time in the intensive care unit so that nurses and doctors can keep a close eye on them. Once a diagnosis is known, a plan to treat any tumour left behind can be made. For benign tumours, there may be no further treatment but for others, radiotherapy or chemotherapy may be required[20].

Radiotherapy

Radiation therapy or radiotherapy is the use of high energy x-rays, gamma rays or protons to destroy tumour cells. This therapy is usually used after surgery to destroy any remaining tumour cells; however it is used as an alternative for people who can’t have surgery. It can also be used alongside chemotherapy. Factors which depict a child’s eligibility for radiotherapy include age, location, type and size of tumour and if the tumour is growing or causing symptoms. These factors also account for the child’s treatment plan. If a child if under the age of 3, it is unlikely that they will be given radiotherapy as it can be damaging to young children and has long-term impacts on cognition, growth and hormone levels[21]. Some tumour types such as “ependymoma may be treated with radiotherapy in younger children if the tumour is in the back of the skull; posterior fossa”[22].

There are internal and external radiation therapies, however in children the process is as follows: Firstly a radiotherapy planning scan (MRI or CT scan) will be taken to show the location and shape of the tumour in the brain. This allows for precise targeting of the radiotherapy beam, the dose required and how often it needs to be given. A treatment mask will then be made to help the child stay still during the entire process. The mask is either made out of Perspex or thermoplastic. For Perspex masks, cool gel is applied to the child’s face followed by strips of plaster and allowed to dry for 30 minutes. The dry plaster is then used to make the Perspex mould. For thermoplastic masks, the plastic is softened in water before being stretched unto the child’s face and allowed to dry. A radiographer will then draw the exact position of the tumour on the mask. After this, the child may be given a general anaesthetic to keep calm if they are very anxious or won’t keep still. The child will then lie on the radiotherapy bed and the mask will be positioned accurately above their head. Staff will need to leave the room but still be able to hear, see and speak to the child. The radiographer will line up the drawings on the child’s mask with the machine and remind the child to remain still whilst the machine zaps the tumour. The child will not be able to see or feel the radiotherapy beams, but they are able to hear the machine. Once the process is finished, medical staff will remove the child’s mask and keep it for further treatment sessions. A typical radiotherapy plan lasts for 4 to 6 weeks and usually takes place once a day every week, excluding weekends with each session or fraction lasting about 5 minutes. Treatment times vary with the child’s treatment plan[23].

The writer of the Astrocytoma diaries describes his radiotherapy experience: “They get you to lie on a table, put a mask on you that secures you to that table, and blast modified x-rays at your brain…it was pretty claustrophobic in that tiny little mask and there were teeny tiny ammonia-like smells at some stages in the treatment…it was like a TV moving around my head, complete with some flashing lights, buzzing and a bit of movement[24]”.

Chemotherapy

Chemotherapy is the use of drugs to destroy tumour cells and is generally used for fast growing tumours and also medulloblastomas that respond well to it. Chemotherapy is usually given by an oncologist or sometimes by a neuro-oncologist and it is used to destroy tumour cells remaining after surgery, slow a tumour’s growth or reduce symptoms. Cytotoxic drugs used in chemotherapy disturb the dividing process of both tumour cells and healthy cells; however, healthy cells are able to repair themselves whilst tumour cells are more likely to die. Chemotherapy drugs can be given orally where the child will be given a pill or liquid to swallow or they can be given via intravenous (IV) injection where the drug is placed into the child’s vein using a needle. Drugs can also be given through a catheter or a port to make the IV injections easier[25]. Factors which depict a child’s eligibility for chemotherapy include the child’s age, type of brain tumour and general health. Chemotherapy oral drugs are often given as an outpatient treatment which means the child does not need to be in hospital to receive them; however, IV injections require the child to be in hospital for several days every few weeks over a period of 3 to 12 months or more.

With IV injections, the child will be put under a general anaesthetic and the IV will be delivered in one of three ways; via central line, PICC line or a portacath. With central and PICC lines (Peripheral Inserted Central Catheter), one end of the tube is passed through the vein in the arm or chest to end up in a large vein near the heart; the other end is left outside the body to deliver the chemotherapy drugs straight into the blood[26]. Portacaths are also similar to central lines, however, the tube doesn’t exit the body through the arm or chest; instead, a small chamber or port is implanted under the skin in the chest, hence it is not visible. The chemotherapy drugs are then injected into the port using a special needle. The type of line used depends on the child’s age and tumour type. With oral drugs, the child must be given the tablet to swallow whole and not crushed. The person delivering the tablet should wear disposable gloves when handling the medication. Chemotherapy drugs have an unpleasant after taste so it is advised to give the child flavoured gum or sweets afterwards to disguise the taste. Drugs which are better at going through the blood brain barrier are used for brain tumours.  Some chemotherapy drugs used to treat brain tumours in children include “Carboplatin, Carmustine, Cisplatin, Cyclophosphamide, Etoposide, Lomustine, Methotrexate, Temozolomide, Thiotepa and Vincristine”[27]. These drugs may be used alone or in various combinations, depending on the type of brain tumour. For example, for children with glioblastomas, the latest standard of care is radiation therapy with low doses of Temozolomide for a period of 6 months to a year. A combination of Lomustine, Procarbazine and Vincristine has been used to help lengthen the lives of patients with grade 3 Oligodendroglia when given before or after radiotherapy. Patients are monitored with a brain MRI every 2 to 3 months whilst actively receiving treatment and the length of time between each MRI scan depends on the tumour’s grade[28]. Jarvis, an 11 year old boy who was diagnosed with a 4cm brain tumour at the back of his brain had 3 monthly MRI scans after his chemo therapy treatment as well as daily growth hormone injections to ensure he was clear of his tumour[29].

Steroids

Corticosteroids are fast-acting drugs used to treat the symptoms of brain tumours. Symptoms are not only caused by the tumour itself; they are also caused by the swelling surrounding the tumour. This swelling puts pressure on surrounding tissues causing symptoms of headaches, sickness and seizures or fits. Treatments such as radiotherapy and chemotherapy may also cause swelling so steroids may be used as part of this treatment to reduce the swelling. Steroids are also given in low dosages if a child is feeling sick or nauseous during chemotherapy. Steroids can be taken orally as tablets or liquid medicine or they can be given via injection to the vein or muscle. The most common way for children to take steroids is in tablet form so tablets need to be small and easy to swallow[30]. Generally, a child will only take steroids for a few days or weeks and will be informed by the doctor about the exact times when they will need to take the steroids. If a child is taking steroids for more than a week, they will be issued a steroid card that contains important information about the type and dosage of steroid that may be needed in an emergency. They are advised to carry the steroid card for up to a year after completion of treatment. If a child misses a dose, they should not be given a double dose next time to compensate for it. It is important for the child to continue taking steroids for as long as the doctor advises them to because when taking steroids, the child’s body will start to “produce less of its own natural steroids so stopping this can suddenly make the child feel sick”[31].

Each treatment for brain tumours in children differ in terms of side effects and recovery. Some side effects may be worse than others or have a longer duration than others. Furthermore, some treatments may cause a child to take longer to recover from than others. I will illustrate the side effects for each treatment mentioned above as well as ways to reduce them.

Neurosurgery

The types and intensity of side effects from surgery vary from person to person and are based on several factors. These factors include; the type and location of the tumour, treatments received before surgery and the child’s general health. Children who have had neurosurgery as a treatment may experience some or all of the following temporary side effects: Sickness and nausea from the anaesthetic, sore throat due to the tubes used to regulate breathing and oxygen levels, headaches caused by swelling in their brain, momentary phases of feeling dizzy or confused, difficulty swallowing and ongoing tiredness. Further side effects include personality changes, poor balance and coordination, speech problems, weakness and epileptic seizures or fits. These side effects usually disappear fairly soon after surgery and can be reduced in a number of ways. Anti-sickness tablets can be given to deal with nausea, painkillers can be used to relieve headaches and the child will have their swallowing checked by a speech therapist to see if there are any associated problems. Surgery also causes swelling in the brain so steroids are given to help reduce this. The most common is Dexamethasone.  Anti-epileptic drugs are also given to children who experience fits or seizures[32].

Radiotherapy

For some children, radiotherapy causes relatively few or no side effects, however for others; the side effects are more severe. “Reactions often start during the second or third week of treatment and may last for several weeks after the final treatment”[33]. Tiredness is a short-term side effect of radio-therapy and can last for several weeks after treatment. Extreme tiredness may also occur several weeks after the child has finished their treatment; this is known as “somnolence syndrome”[34]. Hair loss is another common short-term side effect of radiotherapy and usually starts 2 to 3 weeks after treatment; generally only in the areas where the radiotherapy beams have touched the head. Most will grow back but some can be permanent. Other side effects include skin sensitivity on the scalp, feeling nauseous, reduced appetite and myelosuppression; the slower production of blood cells, which can lead to anaemia, increased risk of infection and/or bleeding such as bruising or nose bleeds. Because a child’s central nervous system is still developing, radiotherapy can cause long term or delayed side effects and these depend on which areas of the brain have been included in treatment. These include effects on brain development and cognitive skills, emotional difficulties, growth and development and puberty. Other possible long term side effects include cataracts, heart conditions and developing a second tumour. Children will have regular check-up appointments to monitor the effects.

Chemotherapy

Side effects of chemotherapy differ from child to child and vary according to the drugs they have been given. As chemotherapy temporarily acts on healthy cells as well as tumour cells, it may cause some unpleasant, short-term side effects. One short term side effect is hair loss but this depends on the chemotherapy drug that the child has. Visual problems are short term side effects and they include blurred vision, dry eyes or sensitivity to light. These symptoms tend to disappear a few months after chemotherapy has ended. Chemotherapy can also cause some children to have skin sensitivity to chlorine and the sun as well as rashes or changes in skin colour. Another common short term side effect is anaemia which leads to increased tiredness, shortness of breath and looking pale; however, the tiredness will wear off once treatment has finished although it may take a few months for the child’s energy levels to go back to normal[35]. Other common short-term side effects include lowered immunity, nausea, hair loss, inflammation of the inside of the mouth (leading to mouth ulcers) and changes to taste or appetite which may lead to diarrhoea or constipation. Some chemo-therapy drugs may cause temporary or permanent infertility. Possible options to prevent this before treatment include sperm banking for boys and egg freezing for girls and this will depend on how urgently they need to start treatment[36]. Anti-sickness tablets can be given to help with nausea. Eye drops can be given to help dry eyes and sunglasses for sensitivity to light.

Treatments for malignant brain tumours in children are not limited to neurosurgery, radiotherapy and chemotherapy only; there are several other fairly new treatments which can be used to treat brain tumours in children, help with identification of brain tumours and also help with side effects.

Proton beam therapy

Proton beam therapy (PBT) is a relatively new type of radiotherapy that uses beams of protons rather than x-rays used in conventional radiotherapy. PBT works by altering the beam energy of protons so that they only release their energy at the exact place where the tumour is located and the main radiation dose is given to just the tumour itself. This means that fewer healthy cells nearby receive a dose of radiation; hence proton beam therapy causes much fewer side effects compared to conventional radiotherapy. PBT does however; require extra training and skill to work out the required depth and dosage of the radiation and is not suitable for all types of brain tumours[37].

Immunotherapy

Immunotherapy, also known as biologic therapy is another type of brain tumour treatment; however it is not commonly used to treat brain tumours in children. Immunotherapy uses substances made by the body or in a laboratory to improve or restore immune system function. It works by slowing or stopping the growth of tumour cells and helping the immune system to work better at destroying tumour cells. Monoclonal antibodies are used in immunotherapy. They attach to specific proteins on tumour cells, hence flag the cells in order for the immune system to find and destroy them. Non-specific immunotherapies include the use of interferons and interleukins which are made in the lab. Like monoclonal antibodies, they also help the immune system to destroy cancer cells; however they can cause flu-like symptoms. Cancer vaccines are also used; “they expose the immune system to a cancerous antigen hence, trigger the immune system to recognise and destroy that antigen”[38].

The need for improved therapies and the significance of the blood-brain barrier were highlighted in a Podcast from Cancer.Net. Dr Susan Marina Chang spoke about the direct injection of a virus that could “multiply specifically in tumour cells and not normal cells, thereby killing the tumour cells and sparing normal tissues and also minimising side effects[39]”. Dr Melissa M Hudson spoke about cancer remoting gene changes in brain tumour cells that were linked to the specific type and location of the tumour and its response to therapy. She also spoke about CAR T cell therapy which involves “taking T lymphocytes and linking them to a specific antibody protein against the cancer cell so it specifically targets and kills the cancer cells…this approach offers hope for children with unresponsive cancer.”[40]

An interesting resource I found was the use of a chemical dye that lights up brain tumours during surgery. A pink drink called 5-amino Levulinic acid (5-ALA) is given to patients before their surgery. This pink drink causes tumour cells in the brain to glow under a special light and helps surgeons to distinguish between brain tumour and healthy tissue so that they can remove more of the tumour[41]. Another very interesting resource was how marijuana could cure cancer written by Joan Bello. Cannabinoids present in marijuana, “cause cancerous tissue to lose nourishment while healthy cells juxtaposed to the cancerous ones are not affected. Chemotherapy cannot discriminate and kills both healthy as well as cancerous tissue[42]”.

In conclusion, the effectiveness of brain tumour treatments in children can be seen in terms of patient’s preference and doctor’s recommendation; how much of the tumour it removes, how quickly it removes the tumour, severity and duration of side effects, reduction in symptoms and likelihood of tumour reappearing after treatment. Some patient’s do not want to sustain scars or bruises from treatment so in this case, neurosurgery would not be the best option of treatment for them as it involves opening the skull which would produces scars on the scalp. However, patient’s preferences for a brain tumour treatment are overridden by doctor’s recommendations. The multi-disciplinary team work together to find out which treatment is most effective for the patient and this is determined by the child’s age, general health and previous treatments as well as the size, type, grade and location of the tumour in the brain, hence why it is important for a scan to be carried out firstly. These factors take into account any side effects of treatment as well as how much of the brain tumour can be removed, not necessarily how quickly the tumour is removed. A doctor’s primary aim is to find the safest, most effective treatment that is likely to remove most of the tumour so that the risks of the tumour reappearing are extremely low.

Neurosurgery is the most effective at removing as much of the tumour as possible, and it greatly improves symptoms compared to other treatments, however, it cannot be used for brain tumours in inaccessible regions and there is a risk of the tumour reappearing in the future. Radiotherapy helps to further remove any remaining tumour when used alongside neurosurgery, and is most effective in removing brain tumours in difficult locations when used independently, however it causes many long term side effects and may be a very uncomfortable process for the child. Chemotherapy is also useful in destroying remaining tumour cells after surgery and could be the more comfortable treatment method if chemotherapy drugs are taken orally. However although short term, the side effects for each chemotherapy drug differ in terms of severity. Proton beam therapy produces the least short term side effects as it uses less harmful proton beams rather than x-rays, however, its long term side effects are not fully known and it is not readily available in most places as it is still relatively new.

I personally believe that an effective brain tumour treatment is one that is able to remove most of the tumour and minimise the risk of the tumour reappearing and also produce the least side effects. I have come to the conclusion that there is no particular treatment that is the most effective, individually in treating malignant brain tumours in children. Rather, a combination of various treatments could be deemed far more effective that just one. In theory, the effectiveness of each treatment is ultimately determined by the nature of the brain tumour and it is the role of the multi-disciplinary team to find the most appropriate treatment for the child.

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[15] https://www.thebraintumourcharity.org/understanding-brain-tumours/getting-a-diagnosis/how-brain-tumours-are-diagnosed/

[16] https://assets.thebraintumourcharity.org/live/media/filer_public/fe/68/fe68969b-a4c6-4403-b595-87a458da7bf0/neurosurgery-for-brain-tumours-v2-child-factsheet.pdf

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[19] neurosurgery-for-brain-tumours-v2-child-factsheet.pdf – Page 6

[20] https://www.macmillan.org.uk/information-and-support/childrens-cancer/cancer-types/brain-tumours.html#318261

[21] https://assets.thebraintumourcharity.org/live/media/filer_public/49/43/4943ff2c-4494-42fb-8b18-ce02d81fbb50/radiotherapy_for_children_v_10.pdf

[22] https://www.thebraintumourcharity.org/understanding-brain-tumours/treating-brain-tumours/child-treatments/radiotherapy/

[23] https://www.thebraintumourcharity.org/understanding-brain-tumours/treating-brain-tumours/child-treatments/radiotherapy/

[24] The Astrocytoma Diaries: Me & My Brain Tumour by Ken Mooney

[25] https://www.macmillan.org.uk/information-and-support/audience/childrens-cancer/treating/chemotherapy.html

[26] https://www.macmillan.org.uk/information-and-support/treating/chemotherapy/being-treated-with-chemotherapy/ways-chemotherapy-given.html

[27] https://www.cancer.org/cancer/brain-spinal-cord-tumors-children/treating/chemotherapy.html

[28] https://www.cancer.net/cancer-types/brain-tumor/treatment-options

[29] https://www.childrenwithcancer.org.uk/stories/patient-story-jarvis/

[30] https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/steroids

[31] https://www.thebraintumourcharity.org/understanding-brain-tumours/treating-brain-tumours/child-treatments/steroids/

[32] https://assets.thebraintumourcharity.org/live/media/filer_public/fe/68/fe68969b-a4c6-4403-b595-87a458da7bf0/neurosurgery-for-brain-tumours-v2-child-factsheet.pdf

[33] https://www.cancer.net/navigating-cancer-care/how-cancer-treated/radiation-therapy/side-effects-radiation-therapy

[34] https://www.thebraintumourcharity.org/understanding-brain-tumours/treating-brain-tumours/child-treatments/radiotherapy/

[35] https://www.nhs.uk/conditions/chemotherapy/side-effects/

[36] https://www.cancerresearchuk.org/about-cancer/cancer-in- general/treatment/chemotherapy/fertility/ coping-infertility

[37] https://www.thebraintumourcharity.org/understanding-brain-tumours/treating-brain-tumours/child-treatments/proton-beam-therapy/

[38] https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/understanding-immunotherapy

[39] Dr Susan Marina Chang, Cancer.Net Associate Editor for Central Nervous System Tumours- Cancer.Net

[40] Dr Melissa M. Hudson, Cancer.Net Associate Editor for Childhood Cancer – Cancer.Net

[41] https://www.cancerresearchuk.org/about-us/cancer-news/news-report/2018-07-12-brain-tumour-surgery-dye-now-available-to-more-nhs-patients

[42] Page 74 – How Marijuana cures cancer by Joan Bello