BRAIN TUMOURS IN GENERAL

WHAT IS A BRAIN TUMOUR?

Dr. Vanaclocha reviewing a case of brain tumour
A brain tumour is an anomalous and unnecessary growth of abnormal cells in the brain. The mechanisms that control cell growth of a tumour cell are damaged, so the cell loses control over its reproductive cycles and reproduces rapidly, again and again, eventually growing into a tumour. A tumour that sits in the brain is called a brain tumour.

TYPES OF BRAIN TUMOUR

Brain tumours can be classified into two main groups: primary and metastatic. Primary brain tumours originate from the cells of the brain or its immediate surroundings, and can be either benign (slow-growing) or malignant (rapid and aggressive growth). Metastatic (“secondary”) brain tumours originate elsewhere in the body -such as breast, lung or colon- and then spread to the brain, generally through the bloodstream. Metastatic tumours are always malignant.

Primary brain tumours
Possible origins of a metastasic brain tumour
Types of primary brain tumours
Possible origins of a metastasic brain tumour
Types of metastasic brain tumours
Types of metastasic brain tumours
MRI image showing multiple brain metastases

Usually, benign tumours, such as neuromas and meningiomas, have slow growth, are well defined with respect to surrounding tissues, and are curable if they can be completely removed by surgical means.

 

Malignant tumours have rapid growth, invade surrounding tissues (so are not well defined), and are not surgically curable since the tumour rapidly reproduces again after the operation. In the brain, this occurs with gliomas.

 

MRI image showing multiple brain metastases
 

In addition, brain tumours, in particular, vary widely in terms of their location, type of tissue involved, and degree of malignancy.

BENIGN BRAIN TUMOURS

Brain meningioma
Meningiomas are tumours originating from the inner lining of the skull. They are almost always benign, and their removal can vary in difficulty depending on their size and location, especially if they affect the cranial base or cavernous sinus.
Acoustic neuroma
Schwannomas are tumours arising from the nerves at the cranial base. They are usually benign, the most common being vestibular schwannomas (also known as acoustic neuromas).

Pituitary tumour

Pituitary adenomas, also referred to as hypofisial tumours, are tumours arising from the pituitary gland.

Though all these types of benign tumours have the potential to become malignant, this is very rare indeed. Unless every tumour cell is destroyed or removed, however, even benign tumours can recur or continue to grow, sometimes many years after their initial treatment.

MALIGNANT BRAIN TUMOURS

Gliomas are tumours that arise from cells in the brain called glial cells, which support and assist nerve cells. There are several types.

Glioblastoma multiforme

The most common gliomas in both adults and children are astrocytomas. These are formed by astrocytes, an abundant type of glial cell named after their star-like shape. They exist in degrees I-IV depending on their malignancy, and the main problem is that their degree of malignancy increases over time. In children most astrocytomas are beningn, but those in adults are normally malignant.

Anaplastic astrocytomas are, in terms of aggressivity, between low-degree astrocytomas and glioblastoma multiforme, which is the most common type of highly-malignant glioma.

Ependimoma
An ependymoma is a type of glioma that arises from ependymal cells, which line the fluid spaces of the brain -where tumours are normally malignant- and spinal cord, where they are generally benign.

Oligodendrogliomas arise from a type of glial cell called an oligodendrocyte. There are several degrees, but they generally respond very well to chemotherapy, unlike other types of glioma.

The distribution of primary brain tumours is:

  • 25.7% meningiomas; most common benign tumour.

  • 23.0% glioblastomas; most common primary malignant tumours in adults.
  • 6.9% cranial nerve tumours (acoustic neuromas, neurilemmomas).
  • 6.2% pituitary tumours.
  • 6.0% astrocytomas.
  • 3.9% anaplactic astrocytomas.
  • 3.0% lymphomas, which arise from a type of blood cell.
  • 2.7% oligodendrogliomas.

The average age at which adults are diagnosed with a primary brain tumour is 53 years; and though gliomas are more common in men, meningiomas are more common in women.

WHAT CAUSES BRAIN TUMOURS?

Tumours appear when damage is produced in genes that regulate cell division and growth or in genes that code for proteins that repair damaged genes. Some people are born with partial defects in one or more of these genes, and sometimes these defects are hereditary and shown by other members of the family.

Brain oedema around a glioblastoma multiforme
Tumour cells secrete substances that provoke an increase in permeability of capillaries to increase the supply of nutrients delivered to them. This causes a brain oedema which will increase the effect of mass and pressure of the tumour on nerve tissue. In addition, tumour cells also secrete angiogenesis factors which encourage blood vessel growth, further increasing their nutrient supply and so allowing them to grow faster. Combating the brain oedema and blocking angiogenesis factors will thus reduce tumour growth.

Moreover, tumour cells secrete substances that prevent the immune system from recognising them and so from destroying them. Attempts have been made to increase our defences against tumour cells, but in the case of brain tumours they have been unsuccessful.

BRAIN TUMOUR SYMPTOMS

Growing tumorous tissue compresses, pushes, invades and induces oedema of the surrounding nervous structures. This causes the malfunction of those nervous structures, and so the symptoms will depend upon the rate and site of growth of the tumour. The most common symptoms include: headaches, nausea, vomiting, neurological deficits (weakness, loss of force or even paralysis of a body part, loss of sensibility, difficulty to speak, loss of vision or hearing, balance problems, memory problems…), epilepsy, behavioural and cognitive changes, changes in character, etc.

In general, symptoms will depend on the size, location, and nature of the tumour. Furthermore, they will be more severe in bigger tumours, ultimately leading to comma and, eventually, death.

HOW ARE BRAIN TUMOURS DIAGNOSED?

MRI image showing a glioblastoma multiforme
The evaluation will include medical history, physical examination, neurological examination and diagnostic tests (MRI and CT scans). Out of the two, MRI provides better images, except in bone lesions, and can provide valuable information about the size and exact position of the tumour.
MRI image showing a glioblastoma multiforme
 

Other diagnostic tests are:

  • Angiogram, which delineates the blood vessels supplying the brain tumour. Nowadays it has been greatly replaced by magnetic resonance angiography, in which the image of the blood vessels is provided by MRI.

  • Positron Emission Tomography (PET), which maps the biological function of the brain, detects subtle metabolic changes, and helps to determine the nature of a tumour.
  • Spectroscopy, which is a study of the tumour’s metabolism through MRI and helps to determine the nature of a tumour.

TREATMENT OPTIONS

Treatment options depend primarily on size, type and location of the tumour, as well as on the age and overall general status of the patient. Options include surgery, radiotherapy and chemotherapy; which can be applied alone or in combination depending on the case.

Corticoid and/or mannitol

Corticoid and/or mannitol can cure the surrounding oedema, acquiring an improvement in symptoms in the majority of patients. This improvement, however, is usually temporary and other, more specific measures must be taken.

Surgery

Craniotomy to remove a tumour
The objective of surgery is to remove as much of the tumour as is possible without injuring the surrounding nervous tissue. Even if the tumour cannot be totally removed, the removal of part of it will reduce symptoms and improve response to radiotherapy and chemotherapy. In many benign tumours, surgery can be a cure. In malignant tumours, however, surgery is NOT a cure; its objective is to diagnose with certainty the type of tumour, to reduce its size to alleviate the symptoms arising from brain compression, and to prepare for other treatments (mainly radiotherapy and chemotherapy) that are more effective if the amount of tumour that remains has been reduced to a minimum. On some cases, the tumour lies on especially delicate areas, such as those that control speech or movement. In these cases, to control the degree of tumour removal while avoiding paralysis or speech loss, an awake craniotomy is performed.
Craniotomy to remove a brain tumour
 

In general, malignant tumours infiltrate in the normal brain, invading surrounding healthy tissue, and the infiltration area cannot be removed because it would lead to grave sequelae or even death. This area of infiltration can be treated by intravenous administration of protoporphyrins (photodynamic therapy) that accumulate in tumour cells, and so when a laser light of a certain frequency is applied only tumour cells die. To check if any tumoural tissue is remaining δ-Aminolevulinic acid can be administered, and so the percentage of tumour removal can be increased, thus prolonging patient survival.

To see if any tumoral tissue is remaining δ-Aminolevulinic acid can be administered. This allows left-over tumorous tissue to be seen in neurosurgical procedures, thus increasing the percentage of tumour removal; which, in turn, prolongs the survival free of disease in patients.

Conventional radiotherapy

Conventional radiotherapy to treat brain tumours

Conventional radiotherapy involves the administration of radiation to the tumour and surrounding tissues, sometimes including all of the brain. Its objective is to stop the growth of tumour cells; and though it cures only a few tumours, in the rest it contributes significantly towards controlling the tumour, thus reinforcing surgery and chemotherapy.

Radiotherapy damages equally normal nervous tissue and tumour cells, but normal cells recover more quickly from the damage. To selectively damage the tumour cells, radiotherapy is fractionated: each dose of radiotherapy injures both normal and tumorous tissue, but by the time a new dose is applied most of the normal cells have already recovered, whereas the tumour cells have not. This is repeated 10 to 30 times, depending on the type of tumour, and hopefully 98% of the tumour cells will be destroyed and 98% of the normal nervous tissue will survive.

 

The risks of radiotherapy include damage to tissues surrounding the tumour and the possibility of developing a second tumour in them, most often about 10 years after the radiation.

Stereotactic radiotherapy

In stereotactic radiotherapy radiation beams are aimed in multiple directions so that they converge at a specific point at which the maximum radiation dose is achieved. Stereotactic radiotherapy fractions the radiation and administers it sterotactically (precisely in space), enabling higher doses of radiation to be delivered and the effects on the surrounding nervous tissue to be reduced. This technique thus increases the safety and effectiveness of radiotherapy, as well as allowing the treatment of tumours that are too large to be treated with radiosurgery.

Stereotactic radiotherapy is most accurate when used for well-defined tumours or tumours that occur in the more delicate areas of the brain, e.g. near the optic nerve.

Radiosurgery

Radiosurgery to treat brain tumours

Radiosurgery is the administration of radiation beams so that they all concentrate in the centre of the tumour. The tumour receives a significant quantity of radiation, but the surrounding normal tissue receives only very low quantities of it. It can be applied alone or in combiantion with radiotherapy. It is used in tumours have a well-defined growth, mainly when surgical removal involves great risk, or in tumour remains, when total removal has not been possible.

 

In tumours with ill-defined borders, radiosurgery can be applied in combination with conventional radiotherapy to administer a greater radiation dosage to a specific area of the tumour.

Radiosurgery to treat brain tumours
 

Intraoperative radiotherapy

Intra-operative radiotherapy to treat recurring brain tumour
Intra-operative radiotherapy involves the delivery of radiation during surgery with an exposed surgical field (open head). This radiation is delivered directly towards the visible remaining tumoural tissue in areas with important functional significance that cannot therefore be totally removed as this could cause sequelae. Intra-operative radiotherapy allows a higher dose of radiation to be administered to destroy any remaining tumoural tissue or stop tumour growth, since it is not limited by the maximum radioactive dose tolerated by the skin covering the area.
Intra-operative radiotherapy to treat recurring brain tumour
 

Interstitial brachytherapy

Brachytherapy using radioactive seeds to treat a glioma

In interstitial brachytherapy a radioactive material is surgically introduced inside the tumour and is maintained for a variable amount of time. It is usually used as reinforcement to other forms of radiation.

Brachytherapy using radioactive seeds to treat a glioma
 

Chemotherapy

Chemotherapy stops the growth of many brain tumours, but, though more drugs are discovered every day, it can cure very few of them. Chemotherapy can be used as a single therapy or, more frequently, as adjuvant (additional) therapy to be combined with surgery and radiotherapy, depending on the type and response of the tumour.

It affects both normal nervous tissue and tumour cells, so the amount of chemotherapy that can be administered is often limited by the collateral effects on normal tissue (bone marrow, lung, heart, or kidney). Tissues with fast-growing cells are the most affected by it; and these include hair, lining of the mouth and digestive track, bone marrow (since it produces blood cells), and tumour cells, which are the most affected. Although chemotherapy can improve overall survival in patients with malignant primary brain tumours, it does not cure those tumours and so is not a definitive solution.  Other times, the objective of chemotherapy is not to destroy the tumour but only to block its growth; and sometimes growth modifiers have been used to stop the growth of tumours that proved resistant other treatments.

During surgery, it is also possible to implant chemotherapy-impregnated wafers in the cavity created after removing the tumour. These wafers will slowly secrete a chemotherapeutic agent to kill any remaining tumoural tissue.

To find out whether the tumour will respond to chemotherapy or to decide on the most suitable chemotherapeutic agent, the tumour cell receptors must be analysed. This enables chemotherapy to be adjusted according to the sensitivity of each particular tumour.

Gene therapy

Gene therapy involves the transfer of generic material to a tumour cell to destroy it, aiming to correct the underlying defects in the genes that lead to the initial formation of a tumour. Other forms of treatment are being intensively researched but, as of today, this treatment has not been effective.

WHAT WILL HAPPEN DURING A SURGICAL PROCEDURE?

Intra-operative picture of the removal of a brain tumour
The surgical procedure involves creating an opening in the skull (“craniotomy”) to be able to access the tumour and remove it. Sometimes an intra-operative analysis of a sample of the tumour is performed to provisionally ascertain its benign or malignant nature; however, the final report is received 4-6 days after the procedure. The difficulty and duration of the procedure will depend on the type and location of the tumour, but they are all long procedures lasting a minimum of 3-4 hours. At times, the procedure is performed under local anaesthesia to be able to monitor more closely the endangered functions of the area to be operated on. This is called awake craniotomy.
Intra-operative picture of the removal of a brain tumour
 
Stereotactic brain biopsy
Sometimes a biopsy is obtained before deciding on the treatment. A biopsy can be performed with a special needle with which a sample (as a thin as a thin noodle and 8mm long) is extracted, and this is known as a stereotactic biopsy. To perform it, a CT or MRI scan is obtained to pinpoint the exact location of the tumour and obtain the exact coordinates of the site at which the sample is to be extracted. Next, the patient is taken to the operating theatre and a small opening in the skull (about 1cm long) is created. Through this opening a special needle is introduced that allows the sample to be extracted. The sample is then sent to the pathologist, who will analyse it and reveal the nature of the tumour.
Stereotactic brain biopsy
 
CT image of hydrocephalus after brain tumour removal
Some patients develop problems with the circulation or absorption of cerebrospinal fluid (CSF), known as hydrocephalus. CSF is produced inside the brain, travels through the ventricles of the brain and down the spine, and is then absorbed by small veins at the surface of the brain. If its flow is blocked, or if its absorption is inadequate, CSF builds up inside the brain and causes pressure on it. This accumulation of CSF can be treated by internal drainage of the fluid to another part of the body, often the peritoneum (“ventricular-peritoneal shunting”). Hydrocephalus may appear at the start, as happens in some tumours such as the colloid cyst of the third ventricle, but it often appears with time, especially if radiotherapy has been administered.
CT image of hydrocephalus after brain tumour removal
 

POSTOPERATIVE RECOVERY

The postoperative recovery will depend greatly on the condition of the patient before the procedure and of the exact location and size of the tumour. After the procedure, in the majority of cases the patient will be transferred to the Intensive Care Unit (ICU), where they are to stay until the next day. This allows a closer surveillance in the first hours, so allowing any early complications that require re-operation to be identified. Back in the Ward, the patient will progressively sit up so that they can stand up as soon as possible. 4-6 days after the procedure the results of the anatomical pathology of the tumour will be revealed, and a therapeutic strategy will be chosen depending on these results. The patient will be discharged 3-10 days after the procedure, though may have other complementary treatments.

WHAT ARE THE POSSIBLE COMPLICATIONS?

There is a range of complications to do with the need of general anaesthesia. The haematoma at the site of the removed tumour, though very rare, requires an urgent re-operation in the majority of cases. The symptoms present before the operation can worsen, or new neurological deficits may appear. Infections can appear, as in any other surgical procedure; they can be slight (infections of the injury of the skin) or severe and deep (meningitis, brain abscess, etc.). Epileptic crises are not rare; and though they may seem quite shocking, in general they are not a bad sign.

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