Metastatic Brain Tumors

OVERVIEW

Tumors that spread to the brain from a primary neoplasm located in other organs of the body are referred to as metastatic brain tumors. They are among the most common intracranial brain tumors encountered by physicians. These tumors are a common complication of systemic cancers and an important cause of morbidity (rate of disease) and mortality (death) in patients.

Approximately 200,000 new cases of brain metastases are diagnosed in the U.S. each year, and the number may be growing with increased awareness and improved diagnostic techniques. In addition, improved chemotherapy treatments of systemic cancers, or malignancies, are allowing longer patient survival; however, these agents fail to protect the brain, leaving it vulnerable to tumor spread.

Risk Groups

Virtually any systemic malignancy can metastasize to the brain, but there are some that have a greater proclivity to do so. Melanoma has a tendency to metastasize to the brain. Other malignancies such as lung, breast, renal and colon cancers are also frequently encountered. Metastatic brain tumors tend to be more common in adults than in children and occur in men and women with equal frequency.

Some differences are seen in the types of primary malignancies responsible for the brain metastasis in the two genders. Lung cancer is the most common source of brain metastasis in males, whereas breast cancer is the most common source in females.

Symptoms

Besides the following symptoms, many patients may experience additional complications caused by the original tumor and its related manifestations.

• Increased Intracranial Pressure (ICP): In most patients, symptoms of brain metastases are caused by the expansion of lesions and increased ICP. The most common symptoms of increased ICP are headache, vomiting and disturbance of consciousness.
• Headache: Headache is the initial symptom in about half of brain tumor patients and is eventually experienced by the majority, at some point.
• Vomiting: Vomiting is an occasional accompaniment to the headache. It is far more common in children than in adults. In children, vomiting may be especially dramatic or forceful, so much so that it may be labeled as “projectile” in nature.
• Alteration in Consciousness: Patients at some point commonly experience alterations in consciousness, including both the level of consciousness and/or its quality. A brain tumor can induce a wide spectrum of changes in mental status, ranging from subtle alterations in personality to states of profound and irretrievable coma.
• Seizures (Epileptic Seizures/Fits): Seizures are associated with brain tumors in almost 35 percent of patients. Age increases the risk of epilepsy caused by a tumor especially in individuals beyond 45 years of age.
• Focal (Specific) Neurological Symptoms: Whereas headaches, altered mental status and seizures may be seen with tumors that occur in many parts of the brain, some symptoms are associated with tumors that occur in specific locations. These focal neurological symptoms affect the side of the body opposite from the side where the tumor resides and may include different modalities of sensation such as tingling and motor changes (hemiparesis).

Radiological Diagnosis

Brain metastasis can be diagnosed utilizing the following tests:

• Computed Axial Tomography (CAT Scan/CT) can be done with or without intravenous contrast and includes many different views of the brain. CTs are frequently the initial diagnostic test utilized.
• Magnetic Resonance Imaging (MRI) makes a clear picture of the brain using powerful magnets and radio waves. With the addition of an intravenous contrast agent, this is the gold standard in testing that provides information about the location, size, characteristics and pressure effects of the tumor.
• If a metastatic tumor is suspected, the treating neuro-oncologist or neurosurgeon may ask for further testing. Additional imaging of the body may be requested and is obtained generally in the form of a CT with contrast of the chest, abdomen and pelvis and a bone scan. These tests allow detection of a primary neoplasm elsewhere in the body. Additional testing may be indicated at times, but this constitutes the basic palette of tests.

Treatment

Treatment varies with the size and type of the tumor, the primary site of the malignancy, its extent both locally and in the rest of the body (staging), the general health of the individual and presence of other significant medical problems. Among the goals of treatment may be to obtain a clear tissue diagnosis, relieve symptoms, improve functioning, and control the cancer and its satellite tumor within the brain.

A tissue diagnosis is critical at times and may have already occurred if the patient has a previously known malignancy. It may be obtained by a biopsy or removal at the site of the primary cancer. On other occasions, a biopsy of the metastatic brain tumor may be performed. If it is large and causing significant pressure effects, it may be removed entirely to relieve pressure while providing adequate tissue for diagnosis.

Once a clear diagnosis of the brain tumor is obtained, staging of the systemic cancer is completed and the patient’s medical condition is stabilized, a multidisciplinary team of physicians will discuss the options to maximize control and possible eradication of the tumor while minimizing morbidity or risk to the patient.

Three critical components of managing patients with metastatic brain tumors are non-chemotherapeutic and chemotherapeutic drugs, surgical techniques to remove the tumor while avoiding any brain damage or injury and radiation.

• Non-chemotherapeutic drugs are given to relieve pain such as a headache, control epilepsy and diminish edema of the tumor. Chemotherapeutic drugs can be given to attack and kill cells that divide rapidly, such as cancer cells. Also, chemotherapy can treat the entire brain while treating multiple cancer sites simultaneously.
• Surgery is an important part of the management for some patients with brain metastasis. Increasing sophistication in neurosurgical techniques, precise navigation systems with intraoperative MRI and improved anesthetic techniques allow neurosurgeons to remove metastatic brain tumors with minimal or acceptable morbidity and with almost no risk of death or mortality. This not only provides tissue for diagnosis but also improves control of the cancer and facilitates the use of additional treatments in the brain. It also allows the oncologist to continue additional treatments to control the systemic disease. Surgery is performed when the treating physician determines that it is likely to lead to greater relief of symptoms than might be achieved by other treatments and possibly extend survival.
• Radiation is also an integral part of managing patients with metastatic brain tumors. Like chemotherapy, radiotherapy can be given as whole brain radiotherapy (WBRT) or in fractioned doses. If there are less than four small (generally less than three centimeters in diameter) tumors, then radiation can be administered in the form of precise, focused beams that target the tumor while sparing the surrounding brain.

Radiation may also be administered following surgical removal of the tumor to further kill any residual malignant cells that may be located within the tumor resection bed. This physical form radiation is known as stereotactic radiosurgery. This treatment is delivered by sophisticated machines in the hands of an experienced neurosurgeon and radiation oncologist with careful input from a physicist. Its main advantage is its ability to treat lesions that are not easily treated by surgery. Also, it is noninvasive, has fewer risks and results in a shorter hospital stay. When there are more than four intracranial metastatic tumors, surgery or stereotactic radiosurgery have a lesser role in treatment. It is felt that more global brain radiation treatments may be better suited for these situations. WBRT is administered in fractions over a course of two the three weeks building up to the maximal and optimal effective dose. Administering the radiation in small fractions each day allows the normal brain to recover while tumor cells are killed.

Other types of treatment may be an option as well. New trials are being performed to use gene therapy for treatment of metastasis. However, gene therapy for brain metastasis is still in its infancy.

Prognosis

Many people with metastatic brain tumors have widespread tumor metastasis. The effectiveness of treatment of brain metastases is almost always determined by how well the primary cancer is controlled. In the absence of control of the primary cancer, treatment of metastatic brain tumors would be a futile endeavor. The prognostic factors are complex and largely depend upon the status of systemic disease, extent of neurological deficit, length of time between first diagnosis of cancer and the diagnosis of brain metastasis, the type of primary tumor and the nature, size and invasiveness of the metastatic lesion, among other things. Hence, careful coordination and communication between the neurosurgeon, radiation oncologist and primary oncologist is essential. Relapse of disease either in the brain or the body is common and hence, frequent and consistent follow-up with imaging studies is also essential.

Organizations such as the AANS provide neurosurgeons with training tools and discussion forums to keep abreast of the latest developments and provide access to the best resources for their patients.