Brain cancer

OVERVIEW

An abnormal growth of cells in the brain is called a brain tumor. Brain tumors may be malignant (cancerous) or benign (non-cancerous).

Suspicions of a brain tumor may first arise from abnormal behavior or other symptoms. Symptoms are typically investigated with a series of tests aimed at making a diagnosis. If a brain tumor is the diagnosis, further information about the cancer cells is necessary to determine the best possible approach to treatment. There are many types of brain tumors that differ based on which type of cells make up the tumor. Also, determining the extent of the cancer helps the doctor to understand the likelihood that the tumor will spread into other brain tissues, a characteristic which may also be referred to as the aggressiveness of the cancer.

The following is an overview of brain cancers, including information on the following topics:

• Symptoms of Brain Cancer
• Tests for Diagnosing Brain Cancer
• The Diagnosis: Brain Tumor Malignancy, Type, and Grade
  • Benign or Malignant?
  • Tumor Grade
  • Types of Brain Tumors
• Introduction to Treatments for Brain Cancer
  • Surgery
  • Radiation Therapy
  • Chemotherapy

SYMPTOMS OF BRAIN TUMORS

Symptoms of brain tumors vary widely depending on the type and location of the tumor. However, some of the most common symptoms are nausea, vomiting, and headaches. These are often caused by increased intracranial pressure, or increased pressure within the skull, which causes compression of the brain tissue.

In addition to increasing pressure, tumors encroach on and/or damage surrounding normal tissue as they grow. In the case of brain tumors, this can result in impaired cognitive functions and associated symptoms. The symptoms associated with brain tumors depend largely on where the tumor is located. The different areas of the brain, called lobes, are responsible for different brain functions. For example, memory is performed primarily in the frontal lobe of the brain (the front part of the brain, located right behind the forehead). A brain tumor in the frontal lobe may be associated with memory loss. However, the areas of the brain perform a variety of functions, therefore, symptoms may be diverse.

Symptoms associated with the main parts of the brain may include one or more of the following:

Frontal lobe (located in the front, behind the forehead)

• Memory loss
• Impaired sense of smell
• Vision loss
• Behavioral, emotional and cognitive changes
• Impaired judgment

Parietal lobe (near the crown of the head)

• Impaired speech
• Inability to write
• Lack of recognition

Occipital lobe (rear and bottom of the skull)

• Vision loss in one or both eyes and seizures

Temporal lobe (located at the side of the head, behind the temples)

• Impaired speech
• Seizures
• Some patients may not exhibit any symptoms

Brainstem (located deep in the brain)

• Irritability
• Difficulty speaking and swallowing
• Drowsiness
• Headache, especially in the morning
• Muscle weakness on one side of the face or body
• Vision loss, drooping eyelid or crossed eyes
• Vomiting

DIAGNOSTIC TESTS FOR BRAIN TUMORS

Doctors may utilize several tests to diagnose a brain tumor. The purpose for conducting diagnostic tests are to first, determine whether an abnormal growth is malignant (cancerous) or benign (non-cancerous), and second, if it is malignant, to determine what type of cancer it is, and how extensively it has spread, which is called the stage of the disease.

The tests that are commonly conducted to diagnose brain tumors include:

• Neurological examination
• Magnetic resonance imaging (MRI)
• Computed tomography (CT)
• Positron emission tomography (PET)
• Biopsy

Neurological examination: The goal of neurological examination is to evaluate the nervous system to determine whether any abnormalities exist. A typical exam involves testing of reflexes, sensation, muscle strength, eye and mouth movement, coordination, and alertness.

Magnetic resonance imaging (MRI): MRI is perhaps the most valuable test that doctors use to diagnose brain tumors. MRI uses a strong magnet and radiofrequency waves to produce an image of internal organs and structures. Under the influence of the strong magnet, the hydrogen atoms in the body line up like compass needles. Next, the patient is exposed to radio waves that cause the hydrogen atoms to momentarily change positions. In the process of returning to their orientation under the influence of the magnet, they emit a brief radio signal. The intensity of these radio waves reflects what type of tissue exists in that area of the body. The MRI system goes through the area of the body being imaged, point by point, collecting information from how the radio waves emit. A computer generates an image of organs and structures based on these radio wave recordings.

MRI is useful for diagnosing brain tumors because it provides accurate:

• Description of anatomy of the brain and shape of possible tumor tissue and definition of the extent of surrounding edema (swelling).

The brain stem is a part of the brain located near the base of the skull. MRI is the best test for identifying brain stem structures and tumors.

Computed tomography (CT): A CT scan is a detailed X-ray. The CT imaging system is comprised of a motorized table that moves the patient through a circular opening and an X-ray machine that rotates around the patient as they move through. Detectors on the opposite side of the patient from where the X-ray entered record the radiation exiting that section of the patient’s body, creating an X-ray “snapshot” at one position (angle). Many different “snapshots” are collected during one complete rotation of the X-ray machine. A computer then assembles the series of X-ray images into a cross-section, or a picture of one small slice of the body. A CT scan is a series of these cross-sectional images.

CT scan is a less expensive test than MRI and provides good definition of extra-axial brain tumors, or brain tumors that are not located deep in the skull. However, this type of scan does not provide effective definition of the extent of swelling and only provides a single plane image, rather than a three-dimensional image. CT scans are useful for identifying acoustical neurinomas or meningiomas.

Positron emission tomography (PET): Unlike techniques that provide anatomical images, such as X-ray, CT, and MRI, PET scans show chemical and physiological changes related to metabolism. This is important because these functional changes often occur before structural changes in tissues. PET images may therefore show abnormalities long before they would be revealed by X-ray, CT, or MRI.

Before a PET scan, a patient will receive an injection of a radiopharmaceutical, which is a drug labeled with a basic element of biological substances, called an isotope. These isotopes distribute in the organs and tissues of the body and mimic natural substances such as sugars, water, proteins, and oxygen. This radioactive substance is then taken up by the cancer cells, thereby allowing the radiologist to visualize areas of increased activity.

After the patient has received the injection, a small amount of radiation is passed through the body, which detects the isotopes and reveals details of cellular-level metabolism. Although the radiation is different from that used in radiography, it’s roughly equivalent to what is administered in two chest X-rays. After the scan is complete, the radiation does not stay in the body for very long.

PET scans are often used after an anatomical scan, such as MRI or CT, has shown that an abnormal mass does exist. With a PET image that reflects the metabolic activity of the tumor, doctors are able to determine whether the tumor is benign or malignant. PET is also used to accurately determine the stage of the brain tumor.

Biopsy: When CT, MRI, or PET scans show evidence of abnormal brain tissue, a biopsy is often necessary to confirm the diagnosis. A biopsy involves removing a sample of the abnormal tissue for examination under a microscope. There are a variety of different types of biopsies and the method used to gain a tissue sample depends on the size and location of the suspected tumor.

• A typical biopsy is the surgical removal of a mass of abnormal cells.
• Fine needle aspiration involves guiding a thin needle into the tumor and gently sucking out cells for microscopic evaluation.
• A stereotactic biopsy utilizes a computer and a three-dimensional scan to direct the placement of the aspiration needle

To learn more about biopsies and stereotactic techniques, go to Surgery for Brain Tumors .

THE DIAGNOSIS: BRAIN TUMOR, MALIGNANCY, TYPE, AND GRADE

The results from diagnostic tests provide detailed information from which a team of healthcare providers can make an accurate diagnosis. The diagnosis includes identifying whether the tumor is benign or malignant , the type of brain tumor , and the tumor grade , or the extent to which the cells have mutated and invaded nearby brain tissue. An accurate diagnosis is critical for determining optimal treatment.

BENIGN OR MALIGNANT?

Brain tumors are designated as benign or malignant based on how cells from the biopsy sample appear under a microscope. Typically, benign tumors are less aggressive and more treatable than malignant tumors.

Benign brain tumors: A benign brain tumor consists of cells that have a normal or almost normal appearance when viewed under a microscope. The tumor is very slow-growing, has distinct borders that form a capsule, and does not spread into adjacent brain tissue. Benign brain tumors grow like a balloon being blown up, with an intact capsule and no direct invasion of brain tissue. However, benign brain tumors can cause brain damage or be considered life-threatening due to their ability to encroach into areas of the brain occupied by normal cells, causing increased pressure on and dysfunction in these cells.

Surgery alone is often curative for benign tumors that are located where complete removal is possible. The most common benign brain tumors are meningiomas and neural sheath tumors (neurilemmoma).

Malignant brain tumors: A malignant, or cancerous, brain tumor grows into and invades adjacent normal brain tissue but rarely spreads outside the brain. Malignant brain tumors can be slow- or fast-growing and are usually life threatening due to their ability to invade and destroy normal brain tissue. Malignant brain tumors can spread to other locations in the brain and spine because they lack distinct borders and are difficult to remove without prohibitive damage to normal brain tissue. Cells from malignant brain tumors can also break away from the initial site and travel to distant parts of the brain and spine by way of the cerebrospinal fluid. However, most malignant brain tumors remain localized, in the area where they began.

There are two types of malignant brain tumors, primary and metastatic. Primary brain tumors originate from cells in the brain and there are many types of these. The most common type of malignant primary brain tumor isglioblastoma multiforme (grade IV astrocytoma ), which make up approximately 20% of all primary brain tumors.

Metastatic brain tumors are any cancers that have spread from another area of the body to the brain. Cancers that commonly spread to the brain include breast and lung cancers.

TUMOR GRADE

The grade of a tumor is determined by the degree to which the tumor cells appear different from normal cells when viewed under the microscope. Grade is an important factor because the extent to which the cancer has differentiated, or mutated compared to normal cells, may help determine the best possible treatment option.

Grade I tumors: Grade I tumors are the least malignant, meaning they appear almost normal when viewed under a microscope. These tumors grow slowly and are usually associated with good long-term survival. Surgery alone can be an effective treatment for this grade of tumor. Pilocytic astrocytoma, craniopharyngioma, and many tumors of neurons, such as gangliocytoma and ganglioglioma, are examples of grade I tumors.

Grade II tumors (well-differentiated): Grade II tumors have a slightly abnormal appearance when viewed under a microscope and are relatively slow growing. While the cells in grade II tumors are not normal, they are still well-differentiated, which means they have distinct boundaries, and thus are not as aggressive as high-grade tumors. However, they can invade adjacent normal tissue, and sometimes these tumors recur as a higher grade.

Grade III tumors (anaplastic): Grade III tumors are, by definition, malignant, although there isn’t always a sharp distinction between a grade II and a grade III tumor. The cells of a grade III tumor are actively reproducing abnormal cells and spreading into adjacent normal brain tissue. These tumors tend to recur, often as a higher grade.

Grade IV tumors (blastomas): The most malignant tumors are designated as grade IV. They have a bizarre appearance when viewed under the microscope, reproduce rapidly, and permeate adjacent normal brain tissues. These tumors induce the formation of new blood vessels so that they can maintain their rapid growth. They also have areas of dead cells in their center. The World Health Organization (WHO) designates grade IV tumors as ‘blastomas’. Glioblastoma multiforme is a grade IV glioma, and the most common example of a grade IV tumor.

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TYPES OF BRAIN TUMORS

The main distinction for brain tumors is whether they originated in the brain or spread from another location to the brain such as the breast or lung. The latter are called secondary or metastatic brain tumors and the cells are identical to the cancer cells from the original location.

Cancers that originate in the brain are called primary brain tumors. There are many different kinds of primary brain tumors and they are classified by the type of tissue in which they begin. The most common brain tumors are gliomas, which begin in the glial cells located in the brain that perform supportive functions for the cells that conduct neural impulses. There are also many types of non-glial brain tumors that arise from other types of cells in the brain; however, most of these tumors are rare. The main types of primary brain tumors include the following:

Metastatic Brain Tumors

Gliomas

• Astrocytomas
• Ependymomas
• Oligodendroglioma
• Mixed gliomas

Non-glial Brain Tumors

• Craniopharyngiomas
• Germ cell tumors
• Meningiomas
• Pineal tumors
• Pituitary adenomas
• Primitive neuroectodermal tumors (PNET)
• Schwannomas

METASTATIC BRAIN TUMORS

Metastatic brain tumors are cancers that have spread from their site of origin to the brain. CNS metastases usually occur by way of the bloodstream. A cancer cell may break away from the original location in the body and travel in the circulatory system until it gets lodged in a small capillary network in brain tissue. Metastatic brain tumors are the most common brain tumor, occurring as much as four times more frequently than primary brain tumors. The cancers that most commonly metastasize to the brain are breast and lung cancer.

For more information, go to the information center for the primary cancer that has spread, such as Breast Cancer or Lung Cancer.

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GLIOMAS

About half of all primary brain tumors and about one-fifth of all primary spinal cord tumors are gliomas, meaning that they grow from glial cells. Glial cells provide supportive functions for the neurons, the brain cells that conduct nerve impulses.

Astrocytomas: Astrocytomas are the most common form of glioma and the most common type of primary brain tumor. These tumors can develop in any part of the central nervous system: the brain, brain stem, or spinal cord.

Astrocytomas are further classified based on how the cells look under a microscope. Cells that are well differentiated mean that they have clear boundaries and structure. They are the least malignant form of brain tumor.

• Non-invasive astrocytoma: Non-invasive astrocytomas are tumors that grow slowly and usually do not grow into the tissues around them. There are two types of non-invasive astrocytomas called juvenile pilocytic and subependymal.
• Diffuse astrocytoma (stage I-II astrocytoma): Diffuse astrocytomas contain cells that are relatively normal and are considered to be low-grade tumors. They grow relatively slowly and may sometimes be completely removed through surgery. However, even well-differentiated astrocytomas can be life-threatening if they are inaccessible. In some cases, these tumors can also progress or recur as higher grade tumors.
• Anaplastic astrocytoma (stage III astrocytoma): Anaplastic astrocytomas grow more rapidly than low-grade tumors and contain cells with malignant traits, meaning they appear very different from normal cells when viewed under a microscope.
• Glioblastoma multiforme (stage IV astrocytoma, GBM): The most advanced stage of astrocytoma is called glioblastoma multiforme, or GBM. These tumors grow rapidly, invade nearby tissue and contain cells that are very malignant. GBM is among the most common and devastating primary brain tumors that affect adults.
• Recurrent glioblastoma multiforme: GBM that has returned or advanced after initial treatment is considered to be recurrent disease. Recurrent GBM may occur after initial treatment of a lower grade astrocytoma, such as diffuse or anaplastic.

Ependymomas: Brain tumors that develop from cells that line the hollow cavities of the brain and the canal containing the spinal cord are called ependymomas. Most of these tumors are usually benign (non-cancerous) and slow growing.

• Well-differentiated ependymoma (stage II): Well-differentiated ependymomas have cells that look very much like normal cells and grow quite slowly.
• Anaplastic ependymoma (stage III): Anaplastic ependymomas are ependymal tumors that do not look like normal cells and grow more quickly than well-differentiated ependymal tumors.
• Ependymoblastoma (stage IV): Ependymoblastomas are rare cancers that usually occur in children. They may grow very quickly.

Oligodendroglioma: Oligodendroglioma tumors begin in the brain cells called oligodendrocytes, which provide support and nourishment for the cells that transmit nerve impulses.

• Well-differentiated oligodendrogliomas are slow-growing tumors that look very much like normal cells.
• Anaplastic oligodendrogliomas grow more quickly, and the cancer cells look very different from normal cells.

Mixed gliomas: Gliomas that occur in more than one type of brain cell are called mixed and may involve astrocytes, ependymal cells, and/or oligodendrocytes. Mixed gliomas include three separate types of tumors:mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma and mixed astrocytoma-ependymoma-oligodendroglioma.

NON-GLIAL BRAIN TUMORS

Craniopharyngiomas: Another tumor that develops in the region of the pituitary gland near the hypothalamus is called a craniopharyngioma. These tumors are usually benign; however, they are sometimes considered malignant because they can press on or damage the hypothalamus and affect vital functions. These tumors occur most often in children and adolescents.

Germ cell tumors: Germ cell tumors arise from developing sex cells, called germ cells. There are different kinds of germ cells, including germinomas, embryonal carcinomas, choriocarcinomas, and teratomas.

Meningiomas: Meningiomas are very common brain tumors that occur in the membranes that cover and protect the brain and spinal cord (the meninges). Meningiomas usually grow slowly and tend to affect more women than men. Most meningiomas are considered to be benign tumors; however, even benign brain tumors can cause disability and may sometimes be life-threatening. Malignant meningioma is a rare tumor that grows more quickly than benign meningiomas. Types of malignant meningioma include anaplastic meningioma, hemangiopericytoma and papillary meningioma.

Pineal tumors: Pineal region tumors are tumors found in or around the pineal, gland, a tiny organ located near the center of the brain that mediates changes in energy with light and darkness, causing sleepiness with darkness and alertness with increasing light. The tumors can be slow-growing ( pineocytomas ) or fast-growing (pineoblastomas ). The pineal region is very difficult to reach, and these tumors often cannot be removed.

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Pituitary adenomas: The pituitary gland is a small, pea-sized structure located at the base of the brain in the center of the head, behind the eyes. It is very important because it secretes several chemical messengers known as hormones, which help control the body’s other glands and regulate growth, metabolism, maturation, and other essential body processes. Cancers of the pituitary gland are called pituitary adenomas. Almost all adenomas are benign, but their slow expansion compresses normal structures that surround it, suppressing normal pituitary function and sometimes causing headaches or problems with vision. Pituitary adenomas rarely metastasize or spread to other areas of the body. Doctors classify pituitary tumors into two groups—secreting and nonsecreting. Secreting tumors release unusually high levels of pituitary hormones, triggering a variety of symptoms.

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Primitive neuroectodermal tumors (PNET): PNETs are rare tumors that occur in children and young adults. The most common type of PNET is medulloblastoma, which arises from developing nerve cells that normally do not remain in the body after birth. These brain tumors begin in the lower part of the brain and may spread from the brain to the spine.

Schwannomas: Tumors that begin in Schwann cells, which produce the myelin that protects the acoustic nerve (nerve of hearing), are called schwannomas and are typically benign. Acoustic neuromas are a type of schwannoma. They occur mainly in adults and affect women twice as often as men.

INTRODUCTION TO TREATMENTS FOR BRAIN CANCER

Brain tumors are typically treated with surgery, radiation therapy, chemotherapy, or some combination of these three modalities.

Surgery: Surgery is the primary treatment for brain tumors that can be removed without causing severe damage.

Many benign (non-cancerous) tumors are treated only by surgery but most malignant (cancerous) tumors require treatment in addition to the surgery, such as radiation therapy and/or chemotherapy.

The goals of surgical treatment for brain tumors are multiple and may include one or more of the following:

• Confirm diagnosis by obtaining tissue that is examined under a microscope
• Remove all or as much of the tumor as possible
• Reduce symptoms and improve quality of life by relieving intracranial pressure caused by the cancer
• Provide access for implantation of internal chemotherapy or radiation
• Provide access for delivering intra-surgical treatments, including hypertherapy or laser surgery

To learn more, go to Surgery for Brain Tumors.

Radiation: Radiation therapy may be used alone or in combination with surgery and/or chemotherapy in the treatment of primary or metastatic brain tumors. The three primary ways that radiation therapy is administered in the treatment of brain tumors are with:

• A machine that directs radioactive beams from outside the body, called external beam radiation (EBRT),
• A computer and image guided technique that directs radiation only at the tumor, calledstereotactic radiosurgery, or
• A radioactive implant that is placed in or near the tumor, called brachytherapy.

EBRT: is the conventional technique for administering radiation therapy for brain tumors, but stereotactic radiosurgery has also become a standard treatment. The most recent advance in the radiation treatment of brain tumors is the brachytherapy technique called GliaSite radiotherapy system, which involves placing a balloon in or near the tumor during surgery and then passing a radioactive material into the balloon for treatment.

Chemotherapy: Chemotherapy is any treatment involving the use of toxic drugs to kill cancer cells. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.

Treating brain tumors with chemotherapy is more complicated than treating tumors elsewhere in the body because of a natural defense system called the blood-brain barrier that protects the brain from foreign substances. The blood-brain barrier prevents foreign substances, such as drugs, from passing from the blood into brain tissues. For a drug to be effective in treating brain tumors, a sufficient quantity must either pass through the blood-brain barrier or be administered in a way that bypasses it altogether. Furthermore, not all brain tumors are sensitive to or respond to chemotherapy, even if the drug does penetrates the blood-brain barrier. Actively dividing cells are the most vulnerable to chemotherapy. Most tumor cells and some normal cells fall into that category.

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