Brain metastasis

Micrograph showing a colorectal carcinoma metastasis to the cerebellum. HPS stain.

Brain metastasis in the right cerebral hemisphere from lung cancer shown on T1-weighted magnetic resonance imaging with intravenous contrast.

A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor.^[1] The original site of the cancer is considered the primary cancer. Metastasis is the most common cause of brain cancer, with tumors originating in the brain being less common.^[2] The most common sites of primary cancer which metastasize to the brain are lung, breast, colon, kidney, and skin cancer. Lung cancer and melanoma are most likely to present with multiple metastasis, whereas breast, colon, and renal cancers are more likely to present with a single metastasis. As primary cancer treatments such as surgery, radiation therapy and chemotherapy have become more effective in the past few decades, people with cancer are living longer after initial treatment than ever before. Brain metastases can occur in patients months or even years after their original cancer is treated. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.^[3]

Symptoms

Because different parts of the brain are responsible for different functions, symptoms vary depending on the site of metastasis within the brain. However, brain metastases should be considered in any cancer patient who presents with neurological or behavioral changes.^[4] Often, patients have no obvious symptoms to alert them that their cancer has spread to the brain.

Brain metastases can cause a wide variety of symptoms which can also be present in minor, more common conditions. The most common symptoms include:

• Paraesthesias: Patients often present with hemiparesis (weakness on only one side of the body).
• New onset headaches: headaches occur in roughly half of brain metastasis patients, especially in those with many tumors.^[4]
• Increased intracranial pressure: may present as nausea, vomiting, and altered consciousness with severe cases resulting in coma.^[5]
• Ataxia: the most likely site of metastasis within the brain is the cerebral cortex, however, when metastasis occurs to the cerebellum, patients will experience various difficulties with spacial awareness and coordination.^[6]
• Seizures: when present, often indicates disease involvement of the supratentorial region of the brain.^[7]

Causes

The most common sources of brain metastases in a case series of 2,700 patients undergoing treatment at the Memorial Sloan–Kettering Cancer Center were:^[8]

• Lung cancer, 48%
• Breast cancer, 15%
• Genitourinary tract cancers, 11%
• Osteosarcoma, 10%
• Melanoma, 9%
• Head and neck cancer, 6%
• Neuroblastoma, 5%
• Gastrointestinal cancers, especially colorectal and pancreatic carcinoma, 3%
• Lymphoma, 1%

Diagnosis

Brain imaging (neuroimaging such as CT or MRI) is needed to determine the presence of brain metastases.^[4] In particular, contrast-enhanced MRI is the best method of diagnosing brain metastases, though detection is primarily done by CT.^[7] Biopsy is often recommended to confirm diagnosis. ^[4]

The diagnosis of brain metastases typically follows a diagnosis of a systemic cancer.^[7] Occasionally, brain metastases will be diagnosed concurrently with a primary tumor or before the primary tumor is found.

Treatment

Treatment for brain metastases is primarily palliative, with the goals of therapy being reduction of symptoms and prolongation of life. However, in some patients, particularly younger, healthier patients, aggressive therapy consisting of open craniotomy with maximal excision, chemotherapy, and radiosurgical intervention (Gamma Knife therapy) may be attempted.

Symptomatic care

Symptomatic care should be given to all patients with brain metastases, as they often cause severe, debilitating symptoms. Treatment consists mainly of:

• Corticosteroids – Corticosteroid therapy is essential for all patients with brain metastases, as it prevents development of cerebral edema, as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and emesis. Dexamethasone is the corticosteroid of choice.^[7] Although neurological symptoms may improve within 24 to 72 hours of starting corticosteroids, cerebral edema may not improve for up to a week. In addition, patients may experience adverse side effects from these drugs, such as fluid retention and myopathy, which can be alleviated by decreasing the dose.
• Anticonvulsants – Anticonvulsants should be used in all of the 30–40% of patients with brain metastases who experience seizures, as there is a risk of status epilepticus and death. This is especially important in other patients with possibly severe seizure types (particularly generalized tonic- clonic, or grand mal, seizures, where the entire brain, not just one local focus or lobe, is pathologically affected). Phenytoin is the most commonly used drug in this setting, but but patients with brain metastases more commonly report experiencing the side effect of a rash while on this medication.^[7] Valproic acid and other anticonvulsants can also be used; newer anticonvulsants generally have the advantage of fewer toxic side effects.

Radiotherapy

Radiotherapy plays a critical role in the treatment of brain metastases, and includes whole-brain irradiation, fractionated radiotherapy, and radiosurgery. For decades, whole-brain irradiation has been advocated for patients with multiple lesions, a life expectancy of less than three months, or a low Karnofsky performance score, and it does appear at least somewhat effective. However, it often causes severe side effects, including radiation necrosis, dementia, toxic leukoencephalopathy, partial to complete hair loss, nausea, headaches, and otitis media. In children this treatment may cause mental retardation, psychiatric disturbances, and other neuropsychiatric effects.^[9]

Surgery

Brain metastases are often managed surgically, with maximum surgical resection followed by stereotactic radiosurgery or whole-brain irradiation delivering superior survival compared to whole brain irradiation alone. Therefore, in patients with one metastatic brain lesion, limited, absent, or controlled systemic disease, a life expectancy of at least 3 months and good performance status might be expected.^[10]

Stereotactic Radiosurgery

Stereotactic radiosurgery is being increasingly utilized for the treatment of a limited number of brain metastases. Stereotactic radiosurgery alone or with whole-brain radiation therapy has been shown to achieve excellent local tumor control. Addition of stereotactic radiosurgery to whole brain radiation can increase the control rate and functional status of patients.^[11]

Chemotherapy

Chemotherapy is rarely used for the treatment of brain metastases, as chemotherapeutic agents penetrate the blood brain barrier poorly.^[1] However, some cancers such as lymphomas, small cell lung carcinomas and breast cancer are highly chemosensitive and chemotherapy may be used to treat extracranial sites of metastatic disease in these cancers.^[1] An experimental treatment for brain metastases is intrathecal chemotherapy, a technique in which a chemotherapeutic drug is delivered via intralumbar injection into the cerebrospinal fluid. Current research on the treatment of brain metastases includes creating new drug molecules to effectively target the blood-brain barrier and studying the relationship between tumors and various genes.^[12] In 2015, the United States FDA approved Alecensa (alectinib) for use in patients with a specific type of non-small cell lung cancer (NSCLC; ALK-positive) whose condition worsened after use or were unable to take another medication, Xalkori (crizotinib).^[13]

Prognosis

The prognosis for brain metastases is variable. It depends on the type of primary cancer, the age of the patient, the absence or presence of extracranial metastases, and the number of metastatic sites in the brain. For all patients combined, median survival is only 2.3 months. However, in some patients, such as those with no extracranial metastases, those who are younger than 65, and those with a single site of metastasis in the brain only, prognosis is much better, with median survival rates of up to 13.5 months.^[1]

See also

• Neoplasm
• Metastasis
• Cancer
• Brain tumor

References