Therapeutic advances in the treatment of brain metastases.

Brain metastases are a frequent sequelae of many solid tumors. Whole-brain radiotherapy (WBRT) has been the standard treatment for decades, with modest long-term complications observed using doses no greater than 3 Gy/fraction. Surgical resection may be beneficial in select populations of patients with single brain metastases, controlled systemic disease, and good performance status. Radiosurgery has demonstrated consistent improvement in local control, with some reports showing a survival benefit when combined with WBRT. However, the role of radiosurgery as a single modality is unclear, particularly given concerns that higher rates of distant brain relapse result in increased risk of neurologic compromise and death from neurologic causes. Increasingly, the importance of neurocognitive assessment with brain metastases is being recognized, and recent data have strongly correlated neurocognitive dysfunction with tumor progression. Systemic agents showing activity in brain metastases including temozolomide, RSR13, motexafin gadolinium, and lapatinib are being explored.