Brain Cancer

What is Brain Cancer?

Brain tumors may be malignant (cancerous) or non-malignant (benign). They result from an abnormal growth of brain tissues. (1)

Since the brain lies within the strong bony cages of the skull, any growth or tumor that occurs within these tissues may create pressure on sensitive brain tissues. This leads to impairment of various brain and nerve functions including problems in vision, speech, balance etc. (1)

Brain structure

The brain is comprised of three major areas of function. The largest part is the cerebrum. It is the brain as we know. It is the source of thinking, memory, speech, learning, reading, writing, cognition and movement by volition.

The lower back region of the brain is called the cerebellum. This controls posture, balance and movement.

The brain is connected to the spinal cord at a region called the brain stem. This controls the most vital functions like heart beats, breathing as well as muscles that control vision, auditory functions, eating and movement.

The brain is bathed in a fluid called the Cerebrospinal fluid (CSF) and is encased in membrane like sheaths called the meninges. (2)

Types of brain tumor

Brain tumors may be of two basic types: primary or secondary. The latter is also known as metastatic.

The primary tumors originate within the brain tissue. These tumors are not spread from one to another and in most cases are not preventable. Metastatic tumors often are a result of cancer that has spread from another area of origin. (1)

Primary brain tumors may originate in the brain cells or nerves, or glands or in the sheaths that cover the brain tissues called meninges. These tumors, if cancerous, may literally erode parts of the brain by causing inflammatory changes apart from creating pressure on the surrounding nerve tissues.

Cause of primary brain tumors

The exact reason for the origin of primary brain tumors is still unknown. These may occur either due to faulty genetics – e.g. in case of neurofibromatosis, Von Hippel-Lindau syndrome, Li-Fraumeni syndrome, Turcot syndrome or tuberous sclerosis etc. or result due to exposure to cancer causing toxins or radiation.

Studies show that radiation exposure to the brain, which is often used for treatment of brain cancers as well, are often responsible for raising the risk of brain tumors in 20 to 30 years.

Radiation exposure as part of occupational hazard in workers at power lines, as well as those with history of smoking, head trauma, hormone replacement therapy, have not been cited as risk factors for brain tumors.

There is a controversy whether use of cell phones and wireless devices are responsible for increased risk of brain tumors. This needs further study.

Infections with Epstein-Barr virus, that raises risk of blood cancer, like lymphoma, may begin in the brain as cancer is also recorded. (3)

Cause of secondary brain tumors

Metastatic brain cancers may spread from an advanced breast, melanoma, kidney, bladder, or lung cancer. The lesions may also spread from sarcomas, testicular or germ cell cancers.

Some cancers, however, do not usually spread to the brain readily. These include prostate and colon cancer.

Sometimes the original site of the tumor that has spread to the brain is not detected. This is called cancer of unknown primary (CUP) origin.

Around one fourth of all cancers that spread or metastasize are brain tumors. These secondary cancers are more common than primary brain tumors and are seen in 10-30% adults with cancer. These metastatic lesions often are seen in end-stage patients and are liable to be fatal. (1, 4)

Brain cancer in children

Brain cancers can occur in children as well. In fact after blood cancers, like leukemia and lymphoma, brain tumors are the third most common cancers in children.

In most of these cases the tumors are primary in nature and the exact cause is unknown.

At present both early detection and treatment of brain tumors and cancers is of paramount importance. In many cases brain cancers and tumors have a tendency to recur after remission. This is especially seen in children with primary brain tumors. (2)

Edited by April Cashin-Garbutt, BA Hons (Cantab)

Brain Cancer Types

Brain tumors are classified based on numerous factors. These may be related to the exact location of the tumor, the nature of the tissues that have turned malignant or other factors.

Classification of brain tumors

Brain tumors are classified based on whether they are malignant (cancerous) or benign (non-cancerous).

A consultant oncologist describes the difference between malignant and benign brain tumors. Source NHS.UK

Brain tumors are also classified based on whether they have originated within the brain tissue or spread from cancers elsewhere. These are respectively known as primary brain tumors or metastatic tumors.

The most common basis for classification is based on histopathology of the tumor. This is essentially the nature of the tissues from which the cancer has originated that help neurologists classify the tumor.

The World Health Organization in 1993 laid out an uniform classification of brain tumors. The classification system is based on the principle that the abnormal cell growth that leads to the brain tumor behaves in a manner that is determined by the cell of origin and sometimes location.

The classification also states that the therapy plan, as well as the prognosis of the tumor, depends upon the exact histopathological classification of the tumor. (1, 2)

Grading of brain tumors

Once tumors are classified they need to be graded. There are numerous grading systems that are based on the microscopic appearance of the tumor. The grading of a single tumor, however, may vary with different grading systems.

Thus, while diagnosing specification of the grading system is of vital importance. According to the World Health Organization, the St. Anne/Mayo grading system best correlated with the predictability of survival of a brain tumor compared to the earlier used Kernohan grading system.

The Kernohan grading system can be used on invasive tumors of astrocytic tumors. It is similar to WHO grading system. (2)

Simply explained grading may be shown as: (3)

  1. Grade I – This is the lowest grade. This means the tumor grows slowly. The cells under the microspope appear almost normal. This type of tumor usually does not spread and may be removed by surgery.
  2. Grade II – The tumor grows slowly but may spread or recur after therapy. These may transform into higher grade tumors.
  3. Grade III – These are fast growing tumors that may spread. The cells do not resemble normal cells.
  4. Grade IV – These are also fast growing and spreading tumors. The tumors may be surrounded by a circle of dead necrotic tissues. They are difficult to treat.

Examples of brain tumor classification

In adults, the commonest brain tumors are either gliomas or meningiomas. Gliomas originate from cells called glial cells. These include a subclassification of cells called astrocytes (with tumors nomenclatured as astrocytomas), oligodendrocytes (called oligodendral tumors) and ependymal cells. Thus there are three major types of gliomas (1)

  1. Astrocytic tumors that may be further classified as –
    1. Astrocytoma - non-cancerous, WHO grade II
    2. Non invasive astrocytomas WHO grade I
      1. hemispheric
      2. diencephalic
      3. optic
      4. brain stem
      5. cerebellar
    3. Cancerous (anaplastic astrocytomas) WHO gade III These may further be classified as –
      1. hemispheric
      2. diencephalic
      3. optic
      4. brain stem
      5. cerebellar
  2. Glioblastomas multiforme (WHO grade IV) that are the most aggressive forms of primary tumors. There are variants of this form called gliosarcomas.
  3. Oligodendroglial tumors that may be made up of a combination of astrocytes and oligodendrocytes. These are thus called mixed gliomas. These may be classified as Oligodendroglioma (WHO grade II) or Anaplastic (malignant) oligodendroglioma (WHO grade III).

Other types of common brain tumor in adults are meningioma and schwannoma. These affect people aged between 40 and 70 years and are usually benign. Meningiomas affect women more commonly while schwannomas may affect both sexes alike.

The tumors may, however, lead to severe complications due to compressive symptoms on other vital and sensitive areas of the brain leading to life threatening or fatal complications. Some of these tumors may also be cancerous and aggressive. (1)

There are also other types of brain tumor, but these are rarer. These include:-

  • cranipharyngiomas
  • ependymomas (WHO grade II)
  • anaplastic ependymoa (WHO grade III) or Myxopapillary ependymoma or subependymoma
  • primary central nervous system lymphomas
  • pituitary (adenomas, carcinomas, cranipharyngiomas) and pineal gland tumors (Pineocytoma, Pineoblastoma or Mixed pineocytoma/pineoblastoma)
  • primary germ cell tumors in the brain

There are also tumors that may affect the Choroid plexus like papillomas or carcinomas, Gangliocytoma, Olfactory neuroblastoma, Neuroblastoma, Retinoblastoma etc. (1, 2)

Stage of brain tumor

After classification of the tumor the patient’s stage of the cancer could be determined for appropriate treatment planning.

For staging the patient needs to be assessed clinically as well as radiologicaly with imaging tests. These determine the extent of spread of the tumor as well as its aggression. Staging determines the prognosis of the cancer as well and provides uniformity of care.

Staging however, is different in other cancers compared to those in central nervous system tumors since most of the other tumors spread rapidly throughout the body.

Cancers and tumors in the brain on the other hand, almost never metastasize. Their prognosis, however, may still be poor because of their ability to grow and pressurize vital areas of the brain to impair functions.

As a consequence of the lack of spread of the CNS tumors there are no formal systems that outline staging of brain tumors.

Factors that may help determine the prognosis of brain tumors in ways akin to staging systems include the patient’s age, level of interference with normal brain activities and functions, type, location, size and grade of the tumor.

Other factors include the resectibility of the tumor. This means that a tumor that can be largely removed by brain surgery carries a better prognosis or outcome. If the tumor has spread to other parts of the brain through the cerebrospinal fluid (CSF that bathes the brain and spinal cord at all times) or has spread to other parts of the body the prognosis is usually poor. (4)

Edited by April Cashin-Garbutt, BA Hons (Cantab)

Brain Cancer Symptoms

It is important to remember that no two persons with brain cancer tend to show same symptoms or signs. In addition, brain tumors and cancers may be sometimes difficult to diagnose as most of their symptoms and signs are commonplace and sometimes overlap with other ailments.

That said, the severity and extent of symptoms caused by brain tumors are linked to the type, grade, location and extent of the tumor.

Commonly the symptoms of the brain tumor is more due to the pressure that the tumor exerts on the surrounding brain tissues than the tumor or cancer itself.

Sometimes the symptoms are caused due to blockage of the flow of Cerebrospinal fluids (CSF) around the brain. The fluid essentially bathes the brain and nerve structures and a blockage in flow leads to build up that may cause swelling of the brain. (1, 2)

Headache is one of the commonest symptoms seen in adults with brain cancer. Persistent morning headaches often accompanied by vomiting or frequent vomiting and nausea should alert an individual and he or she should seek professional help.

Problems with vision like blurring, double vision, hearing impairments, slurring or difficulty in speech are also warning signs.

Other common problems include balance and posture maintenance, numbness or tingling of arms or legs, muscle twitches or jerking and weakness of one side of the body.

Less frequent symptoms include unusual sleepiness, drowsiness, unconsciousness, changes in personality, moods, concentration, memory or behavior. In some patients, brain tumors may manifest as epileptic fits or seizures. (1, 2)

Brain cancer symptoms in children

In children with brain tumors and cancers, symptoms may vary and may often be difficult to understand or report. While most of the symptoms of brain tumors are similar for children as in adults some like increased vomiting, vision, speech, balance, and hearing problems may alert parents.

Sleepiness, loss of activity, weakness of limbs, paralysis, seizures and changes of personality and behavior may also be red flags.

In infants there may be swelling of head size due to swelling of the brain or build up of CSF. This condition is called hydrocephalus and is diagnostic of pathology within the infant brain. (3)

Symptoms in patients with metastatic brain tumors

In patients with metastastic brain tumors the symptoms of brain cancer often accompany symptoms of cancers at other sites.

These include loss of balance and coordination leading to increased falls, fever, fatigue, lethargy, increased severity or new onset headache, memory or cognitive problems or changes in personality, moods or behavior.

Patients may often develop tingling pain, numbness or sensory changes, paralysis, weakness, speech or vision changes, vomiting and nausea. While some of these symptoms are attributed to their primary cancers, they need to seek advice regarding possible brain metastasis. (4)

Edited by April Cashin-Garbutt, BA Hons (Cantab)

Further Reading

Brain Cancer Diagnosis

On presenting with symptoms of brain cancer a battery of tests are advised to reach a diagnosis.

Initial diagnosis methods

The attempt to reach a diagnosis begins with a thorough physical examination. The doctor may also enquire about your history and your relevant family history of brain tumors or cancers. They may also send you for routine blood tests.

A neurological test may also be prescribed. This involves testing vision, alertness, hearing, muscle power and strength, reflexes and coordination.

Eyes are often examined in detail using an instrument called the ophthalmoscope. This examines the back of the eyes called the retina. If the brain tumor creates pressure over the back of the eyes the ophthalmoscopy shows the change. (1)

Radiological and imaging techniques

The most commonly applied techniques are radiological or imaging techniques. These include the MRI or the Magnetic Resonance Imaging technique and the CT scan or the Computed tomography image of the brain.

The MRI is a machine that uses an electromagnetic device that can take detailed pictures of the brain. This may be made more specific by the use of a dye known as a contrast dye that is injected into a blood vessel of the arm or leg. The dye travels up the blood vessels of the brain and shows up a clearer and more detailed picture of the brain with its blood vasculature.

Usually cancers and tumors have deranged blood vessels and this often shows up in dye enhanced MRI images. This type of imaging is often called MRA or Magnetic resonance angiograms.

An MRI with gandolinium is most commonly done. This involves the use of the chemical gandolinium that, when administered, tends to cluster in and around tumor cells highlighting them on imaging.

A CT scan is a less sophisticated imaging technique than an MRI and is like a detailed X ray that shows parts of the brain and the tumor. Contrast dyes may also be used with CT scans. (1)

Spinal tap

A spinal tap or lumbar puncture may also provide aid in diagnosis. In this, the physician inserts a needle in the patient’s back under local anesthesia. This long and thin needle is used to withdraw some of the cerebrospinal fluid. This CSF circulates all over the brain and spinal cord and may provide clues regarding the tumor on examination under microscope.

Neuroendoscopy

Sometimes a neuroendoscopy may be performed. This involves insertion of a fine tube with a camera on its tip. It is inserted into the spaces within the brain called ventricles under the guidance of the camera. This technique may be used to remove a fluid flow blockage, to relieve pressure or to take a sample biopsy. (1)

Biopsy

A biopsy involves removal of a bit of the tumor tissue and examination under the microscope.

The biopsy can reveal the type, grade and original cells of the tumor or cancer. It is sometimes the surest way to diagnose the brain tumor and helps neurologists plan therapy in a patient.

A biopsy may be done during an ongoing brain surgery for the removal of the tumor. In some cases a stereotactic biopsy may also be performed. This includes putting the patient under general anesthesia and using boring instruments under guidance of MRI or CT scan to reach the tumor and take a biopsy specimen from the tumor. This is usually favored in patients who have an inoperable brain tumor.

Tumors or cancers that lie in vital areas of the brain, like the brain stem, may not allow a biopsy at all due to the raised risks of damage and death. In these patients imaging techniques guide management of the patient. (2)

Once the biopsy tissue is extracted it can be subjected to: immunohistochemistry study to detect type of tumor; electron microscopy for cell changes detection; cytogenetic analysis to see cell changes at the level of genes. (3)

Tumor marker tests

There are some tumor marker tests. These are procedures where blood, urine or tissue samples are checked to see if they are high in certain chemicals or markers that are typical of tumors.

These are especially useful in diagnosis of germ cell tumors that may occur in the brain. There are some genetic tests as well that determine the inherited nature of some brain tumors.

Other tests

There are SPECT scans (single photon emission computed tomography scan) that use a camera linked to a computer that makes a three dimensional picture of the brain that shows up the tumor.

A PET scan (positron emission tomography scan) can also be used to diagnose a deep seated brain tumor. This procedure uses radioactive sugar that is injected into a vein for diagnosis. (3)

Edited by April Cashin-Garbutt, BA Hons (Cantab)

Brain Cancer Treatments

Major treatment options for patients with brain cancer include surgery, radiation and chemotherapy. Sometimes a patient may need a combination of these therapies.

Treatment plan usually depends on grade, type, location, size and general health and age of the patient. The patient is counselled and explained in details the benefits and adverse effects that are associated with each of the various modalities of therapy.

Almost all modalities of therapy can be associated with sometimes severe effects that may affect day to day living. Hence, patient counselling is important.

Brain cancer or tumor treatment is often undertaken by specialists like neurologists, neurosurgeons, neuro-oncologists, radiation or medical oncologists and neuroradiologists. On the team there may be a dietician, cousellor for mental health and well being, oncology nurse, physical, occupational and speech therapist. (1, 2)

Brain surgery

Surgical treatment is usually the beginning for most operable tumors. Surgery is commonly used to remove the whole tumour, to remove most of the tumor (called debulking operation), to take biopsy or to remove a growing benign tumor. (1, 2)

Patient’s scalp may be shaved and readied for the surgery. The surgery is commonly performed under general anesthesia. If the entire skull is opened up the procedure is called craniotomy.

Sometimes surgery may be performed by making a small burr hole under the guidance of an imaging technique like MRI or CT scan.

In some cases patient may be awake during the surgery and his or her cognition, speech and memory may be tested as the surgery for tumor removal progresses.

After surgery the incision is closed up with drains places to remove excess accumulated blood and fluids and the head is bandaged.

After brain surgery

There may be initial headache, fatigue or discomfort that subsides within the course of a few days.

Sometimes there may be excess build up of fluids in the brain that leads to pressure. This is tackled with the use of drugs like steroids. Drainage shuts may also be used to ease the swelling.

Brain surgery is associated with risk of infections. This may be prevented by use of antibiotics. Post surgery there may also be some physical impairments. This can be handled with adequate physical therapy and rehabilitation.

Radiation therapy

Radiation therapy involves killing of the brain tumor cells using high energy rays like X rays, gamma rays or proton beams.

A video outlining radiation therapy.

Radiotherapy may be undertaken after completion of surgery, or before if the tumor is inoperable.

Radiotherapy may be applied externally or internally. It may target the tumor alone, tumor along with its surroundings, or whole brain (with or without spinal cord). (1, 2)

The types of radiation therapy include;

  1. External radiation therapy – This technique uses the high energy beams that are targeted towards the tumor. The usual regimen is usually 5 days a week for a few weeks. The therapy lasts only a few minutes. External radiotherapy may be intensity modulated or three dimensional radiation therapy, proton beam therapy, or stereotactic therapy using X rays or gamma rays.
  2. Internal radiation therapy (also known as implant radiation therapy or brachytherapy) - In these cases, small implants or seeds that are radioactive are placed within the brain tumor. The radiation may continue for months and these seeds need not be removed after their purpose is served.

Radiotherapy may lead to common side effects such as nausea, fatigue, hair loss, skin burns and changes like dryness, tenderness or redness that is commonly seen after external radiation.

Sometimes there may be swelling of the brain due to radiotherapy. This may lead to headaches. These can be relieved by steroids. If the pituitary gland is harmed there may be problems with growth - especially in children. Radiation also raises the risk of brain tumors later in life.

Some brain tumors may be treated using radiosurgery. Radiosurgery is a type of stereotactic radiotherapy where the radiotherapy beams are directed specifically at the tumor. It is also called gamma knife treatment. (3)

Chemotherapy

Chemotherapy is the use of anti-cancer or anti-tumor drugs in the management of brain cancer. These may be administered by mouth or via injections – intravenously.

Chemotherapy may be given during or after radiotherapy. These do not require hospital stay and are given to consolidate therapy with other modalities.

Peter Clark, a Consultant Medical Oncologist, describes chemotherapy as a treatment for cancer. Source: NHS.UK

Commonly they cause side effects like anemia, nausea and vomiting, lack of appetite, fever, chills, fatigue, diarrhea, hair loss etc. These drugs may also lead to suppression of immunity that causes increased susceptibility to infections. (1)

Potential new therapies

There are numerous research and clinical trials with new modalities of therapy for brain cancer. Some patients may take part in these trials. For all therapies regular follow up tests that were used for initial diagnosis may be needed to check for cure, remission or recurrence. (4)

Treatment of metastatic tumors depends on the original tumor management. Surgery, radiation and chemotherapy are still preferred modalities of therapy in these patients.

Patients may need care and comfort for widely spread advanced cancers. These include therapy for brain swelling (steroids and diuretics), seizures (anticonvulsants or antiepileptic drugs), pain relievers and other palliative measures. (5)

Edited by April Cashin-Garbutt, BA Hons (Cantab)