Headache

• May be of gradual onset or sudden in the case of hemorrhage Diagnostic Tests

• MRI with contrast enhancement is the gold standard

• CT scans may be used in patients with pacemakers, but may miss small metastases General Approach to Treatment

Patients with brain metastases have a poor prognosis. Untreated patients generally have a median survival of 1 month. The choice of treatment depends primarily on the status of the patient's underlying malignancy and the number and sites of brain metastases. The primary definitive treatments for brain metastases are surgery and radiation therapy. Pharmacologic modalities are primarily used to control symptoms, although cytotoxic chemotherapy plays a limited role in the management.

Nonpharmacologic Therapy

Radiation therapy is the treatment of choice for most patients with brain metastases. Most patients receive whole-brain radiation because the majority of brain metastases are multifocal. Another method known as stereotactic radiosurgery provides intense focal radiation, typically using a linear accelerator or gamma knife, in patients who cannot tolerate surgery or have lesions that are surgically inaccessible (i.e., brain stem). Because brain metastases can occur in up to 50% of patients with small cell lung cancer, prophylactic cranial irradiation is recommended in patients with good performance status who at least partially respond to chemotherapy to both prevent the

development of brain metastases and to prolong survival. Although other cancers can metastasize to the brain, the benefits of routine prophylactic cranial irradiation have only been demonstrated in studies conducted in patients with small cell lung can-

cer.

Surgery plays a key role in the management of patients with brain metastases, particularly in patients whose systemic disease is well-controlled and in patients with solitary lesions. Surgery may also benefit patients with multiple metastatic sites who have a single dominant lesion with current or impending neurologic sequelae.

In cases of elevated ICP due to cerebral herniation, mechanical hyperventilation to decrease the arterial Pco2 down to 25 mm Hg acutely decreases ICP by causing cerebral vasoconstriction. Elevation of the patient bed may also quickly reduce the ICP. It should be noted that these strategies only relieve symptoms and definitive therapy is still required.

Pharmacologic Therapy

Corticosteroids are a mainstay in the management of brain metastases. They reduce edema that typically surrounds sites of metastases thereby reducing ICP. A loading dose of dexamethasone 10 mg IV followed by 4 mg by mouth or IV every 6 hours is typically used. Symptom relief may occur shortly after the loading dose, although the maximum benefit may not be seen for several days (after definitive therapy).

Mannitol is an agent that may be used in patients with impending cerebral herni-ation. Mannitol is an osmotic diuretic that shifts brain osmolarity from the brain to the blood. Doses of 100 g (1-2 g/kg) as an IV bolus should be used. Repeated doses are typically not recommended since mannitol may diffuse into brain tissue leading to rebound increased ICP.43

Twenty percent of patients with brain metastases may present with seizures and require anticonvulsant therapy. Phenytoin is the most frequently used agent with a loading dose of 15 mg/kg followed by 300 mg by mouth daily (titrated to therapeutic levels between 10 and 20 mcg/mL). Diazepam 5 mg IV may be used for rapid control of persistent seizures. Prophylactic anticonvulsants have frequently been utilized; however, a recent metaanalysis did not support their use.44 Thus, because adverse effects and drug interactions are common, the routine use of prophylactic anticonvuls-ants is not recommended.

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