Christopher Dolinsky, MD
Updated by: Lara Bonner Millar, MD & Carolyn Vachani, RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: January 8, 2015
The term “brain cancer“ is commonly used, but can be a confusing term, as it makes all brain cancers sound like one type of cancer. Brain cancer as a term actually encompasses a variety of cancers. There are tumors which arise from the brain itself, known as primary brain cancers, and of which there are several subtypes. There are also brain metastases, which represent the spread of other cancers, such as lung or breast, to the brain. Please refer to the Overview of Brain Metastases for more information on these brain cancers. Brain tumors that commonly occur in children are also discussed separately.
The brain is the organ in a person's skull that controls the functions of all of the other organs. Together, the brain and spine make up the central nervous system. The brain is responsible for the experience of the five senses (taste, touch, sight, hearing and smell). The brain is also the seat of thought, language, personality, creativity and memory. The brain controls movement, sensation, balance, and coordination. In order to do its job, the brain requires an enormous amount of the oxygen and nutrient energy that a person takes in regularly.
The brain is comprised of nerve cells (called neurons), which carry signals, and the cells that support these nerve cells (called glial cells). There are a number of different types of glial cells, all with different names and functions. The glial cells outnumber the neurons in the brain by a ratio of 10:1.
Brain tumors occur when cells in the brain begin to divide out of control and start to displace or invade nearby tissues. Occasionally, brain tumors can spread throughout the body. Tumors that have the potential to spread to other sites of the brain or body are called malignant. When tumors originate in the brain, they are called primary brain tumors. Any of the various normal cell types of the brain can mutate and become a primary tumor, and the particular cell type that makes up the tumor controls how the tumor is likely to behave. Secondary brain tumors, or brain metastases, are those that originate elsewhere in the body and metastasize (spread) to the brain. These are not classified as primary brain tumors, but instead as brain metastases. Brain metastases are actually much more common than primary brain tumors.
Brain tumors are not really thought of as a single disease, but rather as a collection of several diseases that are characterized by cell type, clinical behavior, and type of therapy. One of the special characteristics of brain tumors is that sometimes benign tumors can be as challenging to treat as a malignant tumor, depending on their size and location within the brain. This is because the brain is locked into place by the skull and can't move out of the way if a tumor is growing near it. Even a benign tumor can cause pressure on the brain, and this pressure can be both symptomatic and life-threatening.
Brain tumors generally comprise about 2% of all newly diagnosed adult cancers. There are approximately Nearly 70,000 new cases of primary brain tumors, both benign (approximately 60%) and malignant (approximately 40%), diagnosed ever year in the United States. The peak age at which people are diagnosed with brain tumors varies with the tumor type, however when taking all types into account the average age is about 50 years of age.
Exposure to radiation, both therapeutic (treatment for a disease) and from atomic bomb exposure, has been linked to the development of certain types of primary brain tumors, including meningiomas, gliomas, and sarcomas, particularly if the exposure took place in childhood. Higher radiation doses are generally felt to increase the risk of eventually developing a brain tumor, and radiation-induced brain tumors can take anywhere from 10-30 years to form.
Although many chemicals have been shown to cause brain tumors in laboratory animals, there have never been any associations with chemical exposures proven in human beings. Chemicals that have been shown to cause brain tumors in animals include: n-nitroso compounds, vinyl chloride, and certain organic solvents. However, when examining populations exposed to these various chemicals (like pesticide workers or workers in the petrochemical industry), there has never been any conclusive evidence to suggest that they get brain tumors at a higher rate than people without the chemical exposures.
With the recent popularity of cellular phones, many people have worried that their use may be a risk factor for developing brain tumors, but there has been no conclusive evidence that cell phones increase the risk of brain tumors. There has also been concern regarding exposure to powerful magnetic fields (high power lines) and some sugar substitutes (aspartame), however, there has not been any conclusive evidence linking these factors to increased risk of brain cancer.
Certain hereditary disorders can predispose someone to the development of certain brain tumors, but only about 5% of primary brain tumors have known hereditary factors. Genetic diseases like neurofibromatosis type 1, neurofibromatosis type 2, von Hippel-Lindau disease, and tuberous sclerosis are all associated with an increased risk of developing a primary brain tumor.
Currently, there are no proven strategies to prevent the development of primary brain tumors. Studies of diets rich in anti-oxidants have not shown any benefits in terms of lowering the risk of developing primary brain tumors.
Primary brain tumors are rare enough that they are not screened for with any specific tests. The best way to pick up a diagnosis of a brain tumor early is to see your doctor regularly for a thorough physical examination and to report any new, worrisome symptoms promptly. People with genetic disorders that predispose them for the development of primary brain tumors will often get periodic imaging studies of their brains to look for any evidence of abnormalities.
Unfortunately, the very early stages of brain tumors may not cause any symptoms. As the tumor grows in size, it can produce a variety of symptoms, depending on its location and what areas of the brain it is putting pressure on, including:
Many of these symptoms are non-specific, meaning they could be caused by many conditions; however, your doctor needs to see you if you have any of these problems. Because the brain controls so many different functions, the symptoms caused by brain tumors can be extremely variable. Headache is the most common symptom for patients with brain tumors, occurring in about 50% of cases.
Brain tumors are classified by both the cell of the brain that makes them up, and how the tumor looks under a microscope. Primary brain tumors can arise from any of the cells in the brain. They can come from the neurons, the glial cells, the lining of the brain, or from specific structures in the brain. Glial cells support the neurons of the brain and tumors which arise from these cells are known as glial tumors. The membrane that surrounds the brain can also develop tumors and these are known as meningiomas. There are other types of tumors, which involve other structures of the brain including ependymomas, among others.
About 80% of malignant primary brain tumors arise from the glial cells of the brain and are called gliomas. Unfortunately, a majority of these tumors (54%) are the most aggressive type, called Glioblastoma Multiforme. Astrocytic tumors are another type of glioma, which arise from star shaped cells called astrocytes. When a pathologist (a doctor who studies cells in the laboratory) looks at brain tumors under a microscope, he/she can get a sense of how aggressive the tumor is by the way the cells look, and based on this, assign the tumor a grade. The most common classification system is the World Health Organization (WHO) system, which classifies CNS tumors according to histology (cell appearance under the microscope) as well as tumor grade. The WHO numerical grade represents the overall biologic potential for malignancy (or aggressiveness) from I (benign) to IV (malignant).
The gliomas classified according to their WHO grading:
Other brain tumors include:
When a patient presents with symptoms suggestive of a brain tumor, the physician will perform a thorough history and physical examination. After that, the key to making the diagnosis is appropriate radiology imaging.
Imaging can be performed with either a CT scan or MRI scan. A CT scan is a three dimensional x-ray, and patients will often be injected with a contrast agent to help visualize any abnormalities. CT scans are good tests because they are quick and easy to obtain, and will often be used as the first step towards making a diagnosis. However, an MRI scan is a better test for evaluating abnormalities in the brain. MRI scans utilize powerful magnets to make a three-dimensional picture. An MRI picks up finer detail than a CT scan, and is the study of choice to make the diagnosis of a brain tumor. MRI scans are usually obtained with the use of an injectable contrast agent as well.
There are some further imaging studies that may be used to determine if a mass in the brain is a tumor (as opposed to other causes, such as infection) and if it is a tumor, what type it is. There is a special type of MRI, known as MR spectroscopy or MRS, which allows your physician to learn more about the contents of the mass and helps them determine what the mass is. A functional MRI is another special type of MRI that can help define areas of the brain, which activate when a person moves or speaks. This allows the doctor to “map the brain” and helps the doctor know which areas to avoid during surgery if the tumor is close to a portion of the brain, which is critical for movement or speech.
For many types of brain tumors, the imaging characteristics are distinctive enough to give physicians a pretty good idea of the diagnosis. The primary management of most brain tumors is surgery. If imaging reveals that a mass suspicious for a brain tumor is in a surgically accessible spot, the patient is generally scheduled for surgery without any further diagnostic testing. After surgery, the specimen can be examined under the microscope by a pathologist, and a final diagnosis can be made. However, sometimes, tumors are not in a safe location for surgery. In those cases, in order to make a diagnosis, patients will often need a biopsy. A biopsy is a procedure where a small piece of the tumor is obtained using a needle under image guidance. The biopsy is usually done as a stereotactic biopsy, where the head is immobilized with a frame that is attached to the skull with pins. A scan of the brain is then done with the frame in place. With the same immobilization device on, the person is taken to surgery and the surgeon can use the scan to guide them precisely to the tumor.
Occasionally, your physician may need to examine the fluid that surrounds the brain and spinal cord (cerebrospinal fluid or CSF for short) to see if there are any cancer cells that have spread to this liquid. This can be done with a procedure known as a lumbar puncture, or an LP for short. A needle is inserted between the vertebral bodies (bones of the spinal cord) and into the sack that holds the spinal cord. Some of the CSF is taken out and a pathologist can examine it and determine if there are cancer cells present.
If it is thought that the brain tumor is a metastasis (spread from another area), radiologic imaging may be performed of others areas of the body to locate the primary tumor (where the tumor originated). This can be done with an X-ray or a CT scan. Your physician may also order other laboratory tests to determine if cancer is affecting other organs.
Primary brain tumors do not have a classic staging system the way most other cancers do. This is because the size of a brain tumor is less important than its location and the type of brain cell that makes it up. The likelihood of curing a brain tumor has to do with its location, the cell that makes it up, and how the tumor cells look under a microscope. Your doctor will give you a sense of how dangerous your tumor is and how it should be treated after weighing these factors.
Brain metastases are considered within the staging system of the cancer from which they originated. Thus, the presence of brain metastases automatically makes the primary tumor a stage IV cancer, because stage IV means the presence of any metastasis. For example, a lung cancer that has spread to the brain is a stage IV lung cancer and it is treated according to a lung cancer treatment protocol.
There are a number of different treatments for brain tumors. Some brain tumors are treated with a combination of different types of therapies. The exact location and type of brain tumor will dictate which treatments are recommended.
Whenever possible, surgical resection is recommended for the majority of brain tumors. It is rare that a primary brain tumor can be cured without a surgical resection. However, the location of the brain tumor will dictate whether or not surgery is an option, and to what extent surgery can be performed safely. Some tumors are seated in places in the brain that are just too dangerous to operate on, and surgery cannot be employed. The risks to the patient from surgery depend on the location and size of the tumor. Talk to your neurosurgeon about the specific risks of your planned surgery.
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein or as pills by mouth. One of the special challenges in treating brain tumors with chemotherapy is that there is a natural barrier between the brain and the blood, which blocks many medications from entering the brain. Only certain chemotherapy medications can cross this blood-brain barrier to treat disease in the nervous system. For certain high grade tumors, particularly glioblastoma multiforme, the most commonly used chemotherapy is known as temozolamide, an alkylating chemotherapy. It has been shown to be effective when used in combination with radiation therapy after surgery. Additional temozolamide is given after completing radiation therapy, usually for an additional 6 months.
Other chemotherapy medications used for brain tumors include carmustine (BCNU), carboplatin, CCNU and bevacizumab. Your medical oncologist can explain why he or she recommends one particular regimen over another in your case. In addition, other chemotherapy medications may be used in clinical trials.
Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation for brain tumors comes from an external source (called external beam radiation therapy), and it requires patients to come 5 days a week, for approximately 6 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. External beam radiation therapy is often employed for brain tumors, either as a primary treatment for unresectable tumors or after surgical resection. Typically, the technique of external beam radiation is via Intensity Modulated Radiation Therapy (IMRT). When treating brain tumors close to critical structures within the brain that are more sensitive to radiation damage, such as the nerves of the eyes or the brainstem, IMRT can be used to limit the dose of radiation received by these important structures. IMRT is not beneficial in every case and your physician can discuss this treatment option with you further.
Proton therapy is a type of radiation therapy that works a bit differently than IMRT or standard radiation. The main difference is in the physical properties of the proton beam itself, which allow it to enter the body at a fairly low dose of radiation and increase in the last 3mm of the beam to the dose required for treatment. In addition, the beam then stops, resulting in virtually no radiation to the tissue beyond the target- or no "exit dose" as it is called. This ability to spare healthy tissue is the main difference between x-rays and protons. Research has shown that the biologic effect, or the damage to exposed tissues, is essentially the same for both therapies. This means the therapies will destroy tumor cells in the same manner, but protons should result in less toxicity to surrounding healthy tissues. Proton therapy can be used to treat some types of brain tumors.
Radiation therapy can also be given to a very focused area of the brain using a technique called stereotactic radiosurgery. Stereotactic radiosurgery requires a patient to have a head frame attached, so that a precise map can be made of the patient's head. Radiation is then focused from a variety of different angles to deliver a large radiation dose to the tumor or tumor bed. This can be performed using the same machine that delivers external beam radiation or by a special machine called a gamma knife.
Your radiation oncologist can answer questions about the utility, process, and side effects of any of the above mentioned types of radiation and can recommend the best type of radiation therapy in your particular case.
Once a patient has been treated for a brain tumor, he or she needs to be closely followed for a recurrence. At first, the patient will have follow-up visits fairly often. The longer he or she is free of disease, the less often he or she will have to go for checkups with examinations. The doctor will decide when to obtain follow-up MRI scans.
Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.
This article is meant to give you a better understanding of brain tumors. Use this knowledge when meeting with your oncology team, making treatment decisions, and continuing your search for information.
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