2) Types Of Treatment

Surgery

Surgery as mentioned is the most common treatment for majority of brain tumor which requires entering the brain through various ways, most commonly by making an opening in the skull. Neurosurgeons when possible, try and remove the entire tumor but sometimes this is not possible due to potential risks it may cause, in which case surgery is most often used with radiation therapy. Sometimes a biopsy is done where a small piece of tumor is removed so that it can be examined in order to determine which method should be used for treating it. [5]

Craniotomy

Craniotomy is the most common type of brain surgery. The surgeon removes a bone flap out of the skull allowing them to have access to the brain to operate on. Craniotomy is a critical operation and thus requires patients to have brain scans before the operation in order to determine the exact location of the tumor. Some surgeries can use the guidance of an MRI or CT scan to reach the exact location of the tumor also called stereotactic craniotomy discussed later. Once the brain tumor has been removed, the surgeon puts the area of bone that was removed (called the flap) back into the skull. They are able to put the flap back in place with tiny metal brackets and then stitch the scalp in place. [6]

Temporary side effects of Craniotomy include sickness & nausea, sore throat headaches, difficulty swallowing, tiredness, and dizziness. Some of the more serious complications that rise from a craniotomy include seizures, bleeding, brain damage, stroke, and possible death. Most often, you can expect to stay at the hospital for 1-2 weeks following the surgery. [7]

Craniotomy [6]

Awake Craniotomy

An awake craniotomy surgery will be recommended if they tumor that is being operated on is close to a part of the brain that controls an important function such as a part that controls speech, movement, or feeling. In this type of surgery, patients are usually awake or partially awake throughout the surgery. Usually you have a general anesthetic in the beginning of the operation, followed by a local anesthetic during the operation so that the patient is partially awake, followed by another general anesthetic to finish the surgery off. The surgeon will usually ask the patient to perform tasks while they check the function of the brain. These tasks include things such as speaking, moving parts of your body, or check feeling called functional mapping. The surgeon will ensure that these functions are harmed as little as possible. [6]

Most patients are scared at the thought of having a brain surgery while awake but in fact there is little to worry about as the surgeons are very skilled in this area as this is a commonly used operation type. The side effects are similar to that of a regular craniotomy. [6]

Neuroendoscopy

Neuroendoscopy is a minimally invasive surgery also called a keyhole brain surgery. An endoscope which is a medical instrument made from a long tube, camera, and eye piece is inserted through this keyhole into the brain. There are small forceps and scissors at the end of the endoscope which the doctor uses to cut the tumor. In some cases, a laser can also be attached to the end of the endoscope to cut the tumor. This technique allows surgeons to reach the regions of the brain that are typically not accessible with the traditional surgical procedures, while at the same time confining the invasion to a limited portion of the body. Endoscopes have a variety of viewing angles, thus the neurosurgeons can get a view and detail of the brain not possible any other way. [6]

The main advantage of neuroendoscopy is that it is a minimally invasive surgery. It has small incisions which lead to less scarring and trauma to the brain, it has less pain, better views of the inside of the brain, and shorter recovery time. Despite these advantages, there are also disadvantages such as the need of highly trained neurosurgeons found in highly specialized facilities. The endoscope also needs to be cleaned on a regular basis to get a good view due to blood or fogging. [8]

Despite its advantages, like any other neurosurgery or treatment technique it has its own risks. These include damage to the surround structures. Other risks include difficulty in controlling the bleeding and infection. [8]

Neuroendoscopy [6]

Radiation Therapy

Radiation therapy is usually advised for patients that have brain tumors that are sensitive to radiation. This kind of therapy is given to patients over a several week period with the intention to shrink or kill the brain tumor using x-rays, gamma rays, or protons. Radiation beams are aimed at the specific tumor that is trying to be eliminated, but in some cases where patients have multiple tumors, whole brain radiation is also possible. [2] A single dose of radiation is called a fraction. A typical treatment requires five fractions a week for four to six weeks. [1] Radiation therapy requires planning in order to reduce the amount of impact it has on its surround tissues. A CT scanner is usually used to simulate treatments by testing various heal fields and immobilization devices used to keep the patient from moving. The data gathered from this process can help calculate the appropriate dose before treatment begins. [1]

6 Radiation Therapy Methods

Conventional Radiation Therapy

With conventional radiation therapy, the treatment location is determined using anatomic landmarks and x-rays. This technique is most viable when doing whole brain radiation therapy for brain metastases. In order to have more precise targeting, there are better methods. [4]

3D Conformation Radiation Therapy (3D-CRT)

This process uses both a CT and MRI to create a 3D model of the tumor and the healthy tissue surrounding it. This model then allows the doctor to aim the radiation beams directly at the tumor, thus reducing the unnecessary radiation to healthy tissue. [4]

Intensity Modulated Radiation Therapy (IMRT)

This is a more recent and advanced type of 3D-CRT that can target the tumor better. It can deliver higher doses of radiation to the tumor while giving less to the surrounding healthy tissue. Using IMRT, radiation beams are broken down into smaller beam and intensities. This allows for a better concentration on the tumor. [4]

Radiation Therapy [3]

Proton Therapy

The proton therapy uses high energy protons rather than x-rays to eliminate tumor cells. This type of therapy is usually used when the location of the tumor is critical such as ones that have grown near a bone or near the optical nerve. [4]

Stereotactic Radiosurgery

This type of radiosurgery is best for a tumor that is only in one area of the brain. There are different types of stereotactic radiosurgery equipment that can give a single high dose radiation directly to the tumor and not the healthy tissue surrounding it. [4]

Fractionated Stereotactic Radiation Therapy

Fractionated stereotactic radiation therapy means that the radiation is decided into fractionated or small daily doses over several weeks in contrast to 1 day radio surgeries. This is used for tumors close to optic nerves or brain stem. [4]

Side Effects

Radiation therapy most often has short term side effects that go away soon after the radiation treatment is completed. These include fatigue, mild skin reactions, hair loss, upset stomach, and neurological symptoms. Longer term side effects of radiation depends on how much healthy tissue received radiation therapy and include memory and hormonal problems. Radiation therapy is usually not given to children younger than 5 as their brain is still developing and thus can cause serious problems. [4]

Chemotherapy

Chemotherapy uses drugs to attack and kill cancerous cells using one or more anti-cancer drugs either orally or by injections directly into the blood. Chemotherapy my be given with either a curative intent or to prolong life and reduce symptoms. For some people, intrathecal chemotherapy which is injecting the drugs into the cerebrospinal fluid can be given to administer the drugs.

Chemotherapy is usually given in cycles which is usually followed by a recovery period and then repeated. Most often, drugs can be given at a doctors office allowing the patient to go home right afters, however it does depend on the drug and the dosage used. [5] Usually chemotherapy is used alongside other treatments such as radiation therapy.

Chemotherapy drugs have the greatest effect on cells that reproduce rapidly, similar to those found inside a tumor. However, these drugs are usually unable to tell the difference between healthy cells and tumor cells. Thus some common side effects are vomiting, diarrhea, fatigue, fetal injury, while more dangerous risks include coma, stroke, damage to internal organs, brain swelling, and more. [9]

Carmustine wafers

Carmustine wafers are dissoluble wafers that contain carmustine which is the chemotherapy drug. Once a surgeon has removed as much of a brain tumor as possible during a craniotomy surgery discussed above, the Caramistine Wafers can be placed directly on or next to the parts of the tumor that can not be removed. Unlike IV or oral chemotherapy that reaches all areas of the body, this type of therapy concentrates the drug at the tumor site, producing few side effects in other parts of the body. [10]

Chemotherapy Side Effects [9]

Targeted Therapy

Targeted therapy is the use of medicines that target the parts of cancer cells that make them unlike normal cells. It basically targets cells that help tumors grow and spread. Targeted therapy can help when other treatments are not working as well. They can also have less-severe side effects than standard chemotherapy medicine. For brain tumor treatment, currently there are two targeted therapy medicines called Bevacizumab and Everolimus. [11]

Bevacizumab (Avastin)

Bevacizumab is a synthetic version of the immune system protein found in the body called monoclonal antibody. This antibody targets vascular endothelial growth factor (VEGF), a protein that helps tumors form new blood vessels to get nutrients as tumors require new blood vessels to grow.

Studies have shown that when added to chemotherapy, this drug can help extend the time until certain brain tumors start growing again after surgery, but it does not seem to help people live longer. It can also help lower the dose of the steroid drug dexamethasone needed to help reduce swelling in the brain, which is especially important for patients sensitive to steroid side effects.

Bevacizumab is a drug that is administered intravenously once every two weeks. Common side effects of this drug include:

high blood pressure
bleeding
tiredness
low white blood cell count
headaches
loss of appetite
diarrhea

More rare but serious problems includes hear problems and holes in the intestine. [12]

Everolimus (Afinitor)

Everolimus works by blocking a cell protein known as mTOR, which normally helps cells grow and divide into new cells. For subependymal giant cell astrocytomas (SEGAs) that can’t be removed completely by surgery, it may shrink the tumor or slow its growth for some time, although it’s not clear if it can help people with these tumors live longer.

Everolimus is taken as a pill once a day. Common side effects include mouth sores, increased risk of infections, nausea, loss of appetite, diarrhea, skin rash, feeling tired or weak, fluid buildup (usually in the legs), and increases in blood sugar and cholesterol levels. A less common but serious side effect is damage to the lungs, which can cause shortness of breath or other problems.

There are other methods that are currently in clinical trials but targeted therapy does seem to be a promising alternative. [12]

Steroids

The main use of steroids in brain tumour treatment is aimed at reducing the side effects, rather than treating the tumours themselves. Steroids are naturally they produced in the adrenal gland; however, those administered in cancer treatment are artificially made in a laboratory. These substances can reduce the swelling of brain tumour tissue due to surgery or radiation, and thus reducing feelings of headache, nausea and seizures, produce more energy, regulate blood pressure, control mood and behaviour [13]. These are fast-acting drugs, but when introduced into the body, the organism will produce less of its own, therefore their dosage has to be closely monitored. Steroids can be taken orally or intravenously.

The types of steroids used in cancer patients are called corticosteroids ( prednisolone, methylprednisolone, dexamethasone).

However, the use of these substances can have side effects such as increased risk of infection(especially for viral infections such as chicken-pox, shingles and measles), mood changes, change in blood sugar level, swollen limbs, increased appetite, weight gain [14].

Alternating Electric Field (Tumour Treating Fields)

This method uses low-intensity electric fields to treat cancer, targeting rapidly-dividing cells and inhibiting mitosis (cell division cycles). However, this method is often used following other methods.

Image source: [15]

The device used is a cap that is secured on the scalp that transmits targeted electromagnetic waves in the range of 100 to 300 kHz into the brain. TFF may halt the reproduction of cells or even induce immunogenic cell death. The device has to be worn at least 14 hours a day, and at least for 4 weeks. [16]

The most common use case for this device is recurrent glioblastoma. The method was approved for clinical use in 2011.

The side effects caused by this treatment option are very limited, the most common being grade 1 or 2 scalp irritation.[17]

The electric field applied is modelled for maximum efficiency in treating the tumour. Therefore, the brain's electric properties need to be determined beforehand, and modelled.

The studies proving the efficiency of this method seem to have been biased, therefore further research needs to be carried out. Future tests combining TFF and immune therapies could potentially prove an efficient option.

Image source: [17]

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