Medical Management of Brain Metastases from Lung Cancer

Abstract

Brain metastases are a frequent complication in patients with lung cancer and a significant cause of morbidity and mortality. Brain metastases are found in about 10-25% of patients at the time of diagnosis, and approximately 40-50% of all patients with lung cancer develop brain metastases during the course of their disease, with greater frequency at autopsy (approximately 50%) than predicted from the presence of symptoms (1). The incidence of brain metastasis is increasing mainly due to longer patient survivals resulting from newer treatment modalities. Most patients with lung cancer metastatic to the brain have multiple lesions (2). Brain metastases are usually associated with poor outcomes and shortened survival of 3 to 6 months. Standard treatment options include symptomatic therapy with corticosteroids and whole-brain radiotherapy (WBRT) (3), and more aggressive approaches such as surgery or radiosurgery are indicated in a subset of patients (4,5). Surgical resection of accessible brain metastases combined with postoperative WBRT is the management of choice for a single metastasis (6). However, radiosurgery for brain metastases produces high rates of tumor control similar to the rates obtained by excisional surgery (7). Patients with multiple brain metastases are commonly treated with WBRT for the palliation of symptoms (8). The role of radiosurgery for multiple brain metastases is less clear, but it can be effective (9). The poor outcomes and relapses following WBRT alone indicate a need for new therapeutic options. Generally, poor prognosis occurs not from cerebral problems, but from extracranial metastases, and death is caused by systemic disease combined with the neurological condition (10). However, treatment with systemic chemotherapy is controversial because chemotherapeutic agents may not cross the blood-brain-barrier (BBB) and therefore are less effective against central nervous system (CNS) disease than against extracranial, systemic disease. However, the BBB is partially disrupted in brain metastases (11) and similar concentrations of chemotherapeutic agents are found in intracerebral and extracerebral tumors (5). Brain metastases resulting from both non-small-cell (NSCLC) and small-cell lung cancer (SCLC) are susceptible to systemic chemotherapy, and cerebral response rates up to 50% were observed even in second-line treatment of NSCLC and SCLC (1,10,11). Still, medical therapies for brain metastases are neither well-studied nor established. Here, I analyze the impact of medical treatment on survival by reviewing recent articles and provide recommendations for the management of patients with brain metastases from lung cancer.