A brain metastasis is a tumor that develops from cancer cells that have spread from other cancerous sites in the body to the brain, usually through the bloodstream. In contrast, a tumor that arises from the brain or surrounding tissues is referred to as a primary brain tumor and, is by definition, not a brain metastasis.
Incidence of brain metastasis
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Brain metastases occur in approximately 20 to 40 percent of patients with cancer. Up to 75 percent of afflicted patients have multiple lesions. Although the most common sources of brain metastases in adults include lung, breast and skin (melanoma) cancers, the primary site or tissue origin of the metastases is unknown in up to 15 percent of patients. As a general rule, almost any systemic cancer is capable of metastasizing or spreading to the brain. It is important to identify the primary source of a brain metastasis, as this information is often critical to selecting the most effective treatment options.
Symptoms of brain metastases
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Approximately two-thirds of brain metastases are symptomatic at some point. Symptoms are caused by increased intracranial pressure, and/or focal irritation or destruction of brain tissue.
Increased intracranial pressure can be caused by tumor growth, swelling (edema) induced in the adjacent brain tissue, obstruction of cerebral spinal fluid pathways (hydrocephalus) or a combination of these effects. Typically, patients may experience nonspecific symptoms such as headache, nausea, vomiting, mental status change and lethargy.
Focal irritation or destruction of brain tissue produces varied symptoms, such as seizures, paralysis, visual impairment, epileptic seizures, gait disturbances or other neurologic deficits, depending on the specific location of the metastatic lesion.
How brain metastasis is diagnosed
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When a patient presents with any of the symptoms described above, doctors generally recommend a brain imaging study.
There are two primary choices for such imaging:
- computed tomography (CT) scan (also commonly referred to as a CAT scan)
- magnetic resonance imaging (MRI) scan.
CT scanners use X-rays projected from a hollow tube to produce cross-sectional images, or slices, of almost any part of the body. These images depict the brain tissue in high detail, unlike the routine X-rays commonly used to evaluate a patient for a broken bone. When a brain tumor is suspected, intravenous iodinated contrast (dye) is often injected into the patient immediately prior to the CT scan. This special dye enhances visualization of abnormalities, such as tumors, on the scan. During the CT scan, the patient lies still on a table that slides into a large, circular opening in the scanning machine. As the table moves through the doughnut-like opening of the CT scanner, a series of X-ray beams pass through the body from many different directions.
Another type of imaging tool commonly used to diagnose brain metastases is magnetic resonance imaging. MRI uses a strong magnetic field and radio waves, rather than X-rays, to produce detailed images of soft tissue organs, such as the brain. Specialized detectors in the computerized MRI scanner record and process fluctuations in the intensity of radio waves, thereby making it possible to generate a series of cross-sectional images that can be interpreted by doctors. Most patients diagnosed with an abnormality on a CT scan will typically undergo an MRI as well.
During an MRI scan, the patient must lie flat on a table that slides into the bore (tunnel-like structure) of the scanner. Individuals suffering from claustrophobia (fear of small, enclosed spaces) may have difficulty undergoing an MRI, but with mild sedatives, most patients can be imaged. In the occasional patient for whom claustrophobia is more severe, an "open" MRI (i.e., one that is not enclosed), can be used for imaging. A typical scan of the brain takes approximately 30 minutes. As with CT, contrast is usually injected to improve the visibility of most tumors. Unlike the dye used with CT scans, MRI contrast (gadolinium) does not contain iodine, and allergies to it are extremely rare. Because of the extremely powerful magnetic field that exists within the scanner, MRI cannot be used on patients with pacemakers or other surgically implanted metal devices. MRI centers should routinely ask patients about their medical history to establish the safety of MRI in a given patient.
Treatment options for brain metastases
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The various treatment options that are available for treating brain metastases will be discussed in the following sections. In arriving at a specific treatment plan, both the doctor and patient need to consider the precise location(s) of the metastatic tumor(s), patient age, tumor type, status of the cancer in other parts of the body, and general health of the patient.
Oral steroid medication
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Treatment with oral steroids (e.g., Decadron, dexamethasone, prednisone) is an important part of the management of almost all patients with brain metastases. Metastatic tumors very frequently cause brain edema, or a breakdown in the blood-brain barrier. This phenomenon results in an abnormal accumulation of fluid in the tissue of the brain. Brain edema is harmful because it causes the brain to function abnormally or leads to an increase in pressure within the cranium, often manifested by headaches. By stabilizing the blood-brain barrier, steroids reduce swelling and its associated symptoms. In the short term, such therapy can be very effective for treating swelling. However, steroids alone are rarely an adequate longer-term treatment for brain metastases. This is because larger doses of steroids are needed over time to maintain a therapeutic effect, and as the dosage is increased, disabling side effects become increasingly apparent. The potential side effects of steroid use need to be discussed with the prescribing doctor.
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Clinical studies have shown that surgery is beneficial for managing select patients with brain metastases.
The most widely accepted indication for conventional surgery is for patients who have:
- A single metastatic tumor located in an area of the brain that is safely accessible by open surgery
- No evidence of cancer elsewhere in the body. Aggressive surgical removal of the metastatic tumor in such favorable situations results in better outcomes compared to radiation therapy. Only very rarely is removal of more than one brain metastasis indicated. When a diagnosis of metastasis cannot be established by imaging alone, or the origin of the tumor is in doubt, removal of the brain metastases has the advantage of providing pathological material (tissue samples) for a definitive diagnosis. The risks of surgical removal vary considerably depending on the health of the patient and location of the tumor. A thorough discussion of potential risks with the treating surgeon is always warranted prior to any surgical intervention.
Whole brain radiotherapy
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Radiation therapy has been a mainstay of treatment for brain metastases for many years. It is often referred to as whole brain radiotherapy, and involves daily administration of radiation to the brain over a period of several weeks. The treatment takes advantage of the fact that cancer cells are more prone to radiation injury than a normal brain. Traditionally, whole brain radiation therapy has been the primary mode of treatment for the vast majority of patients with brain metastases. Whole brain radiotherapy can produce significant shrinkage of many brain metastases tissue, and in doing so, relieve a patient's symptoms. However, such treatment often does not completely eliminate the tumors, and recurrence is not uncommon. Meanwhile, there are significant, albeit oftentimes subtle, cognitive side effects to whole brain radiotherapy that become increasingly apparent over time. Spreading treatment over longer periods of time may alleviate some of the injury to normal brain tissue that is induced by radiation therapy.
In recent years, a growing body of clinical evidence has emerged suggesting that whole brain radiotherapy may be withheld, or at least delayed, in those patients with three or less brain metastases that have been treated with stereotactic radiosurgery (discussed below). This finding is important because radiosurgery involves selective targeting of only the tumor with radiation, whereas whole brain radiotherapy irradiates the entire brain. As a result, the use of radiosurgery alone alleviates much of the risk of damaging normal brain with radiation. While the strategy of avoiding whole brain radiotherapy is being pursued more and more, it remains a point of debate whether it is best to treat with radiosurgery alone or in combination with conventional radiation. The risks and benefits of these different strategies should be discussed in detail with the patient's radiation oncologist and neurosurgeon.
Although there are several types of devices used to administer radiosurgery, the principle of delivering a high dose of radiation to a precisely localized target is the same. Some technologies, like the Gamma Knife, use radioactive cobalt as a source of ionizing radiation. A linear accelerator produces the radiation in other devices. Regardless of the source of radiation, nearly all methods of radiosurgery use stereotactic frames that are anchored to the patient's skull with invasive aluminum or titanium screws. The frame serves to accurately localize the tumor in space and immobilize the patient's head. The CyberKnife® is the only radiosurgery device that does not require such a frame for precise targeting. As a result, this instrument uniquely enables doctors treating gliomas to divide a large radiosurgical dose into more than one stage or fraction-staged radiosurgery. Staged CyberKnife radiosurgery is of particular benefit to patients who have previously received large doses of conventional radiation therapy and patients with gliomas near critical areas of the brain.
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Radiosurgery is an important therapy for the treatment of metastatic brain tumors. This procedure enables doctors to focus a high dose of radiation on a tumor while minimizing radiation exposure to surrounding normal tissue. Radiosurgery involves the precise delivery of multiple beams of radiation, such that each beam enters the body from a different angle and passes through the tumor. This makes it possible to "concentrate" the radiation at the point of beam intersection (at the tumor) while giving the rest of the brain only a small overall dose. The accuracy with which radiosurgery is targeted minimizes the risk of harming surrounding healthy tissue, and, as a result, larger and more effective doses of radiation can be administered. These unique advantages of radiosurgery make possible the most precise and aggressive radiation treatment available for brain metastases. Meanwhile, unlike whole brain radiotherapy, which must be administered daily over several weeks, radiosurgery treatment can usually be completed in one to five sessions. Radiosurgery can be used alone to treat brain metastases, or in conjunction with surgery or whole brain radiotherapy, depending on the specific clinical circumstances.
Radiosurgery is a widely accepted treatment for a single metastatic brain tumor that cannot be safely removed by traditional surgical techniques. It is also used frequently when a patient has more than one metastatic tumor, a condition that usually precludes surgical treatment. In addition, many clinical series have now shown that radiosurgery may be as effective as traditional surgery for the eradication of single metastatic brain tumors, whether or not the tumor can be safely removed by surgical means. Finally, radiosurgery can also be used in conjunction with surgery to eliminate another inoperable tumor or to treat a tumor that persists or recurs following a surgical removal.
The advantage of radiosurgery over traditional surgery is that no skull opening, or craniotomy, is required, and as a result, there is no surgical trauma to the normal brain. Furthermore, the recovery time from radiosurgery is much shorter than that from standard surgery. Because radiosurgery does not require a patient to be put under general anesthesia (which entails a breathing tube), radiosurgery is an important alternative to surgery for patients who are not in otherwise good health. Finally, it is much easier to treat more than one metastasis with radiosurgery than it is with conventional surgery.
Advantages of CyberKnife radiosurgery for treatment of brain metastases
There are several methods of delivering radiosurgery to a brain metastasis. All other available radiosurgical devices require the attachment of a painful metal frame to the patient's skull to localize (locate) the tumor. In contrast, CyberKnife radiosurgery is completely painless and bloodless; typically, no sedation or anesthetic is needed. In addition, because the CyberKnife does not require a frame for tumor localization, the overall length of the procedure is generally much shorter than that required by frame-based radiosurgical methods. Moreover, the advanced image guidance system used by the CyberKnife allows multiple metastases that are widely dispersed throughout the brain to be more easily treated in a single radiosurgical session. The vast majority of metastatic brain tumors are treated in a single outpatient visit, usually requiring less than an hour to complete. Patients generally return home immediately following treatment, often resuming normal activities.
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