Current strategies in whole-brain radiation therapy for brain metastases.

Whole-brain radiation therapy (WBRT) has been the primary treatment for patients with brain metastases for more than 50 years and provides effective palliative relief in most patients. Although advancements in radiotherapeutic technique continue to improve local and locoregional control, median survival for patients treated with WBRT monotherapy remains fixed at approximately 4 to 6 months. Key issues in the use of WBRT include optimizing its efficacy when it is used in conjunction with surgery, radiosurgery, radiosensitizers, and new chemotherapeutic agents. These multimodal approaches to brain metastases have resulted in significant increases in the median survival time in many patients. Radiosurgery is part of a continuing effort to improve the effects of radiation therapy, especially in brain metastases. The optimal combination of WBRT and radiosurgery remains to be elucidated, including appropriate timing or sequence and use in conjunction with other modalities. Newer radiosensitizing agents (e.g., efaproxiral [RSR-13] and motexafin gadolinium) have shown promise in the treatment of brain tumors, especially in specific patient subsets. Recently developed systemic chemotherapy agents, such as temozolomide, which crosses the blood-brain barrier, have a synergistic effect on brain metastases when used in conjunction with radiation. In addition, the use of interstitial chemotherapy agents provides highly focused local chemotherapy in the brain without increasing systemic toxicity; carmustine polymer wafer, in combination with WBRT, has shown promising results in treating brain metastases.