Current therapeutic approaches in patients with brain metastases.

The development of brain metastases is often viewed as the end stage of a disease course and engenders skepticism about the efficacy of treatment. Aggressive management of brain metastases is effective in both symptom palliation and the prolongation of life. The majority of patients with controlled intracranial metastases will expire from systemic disease rather than from recurrence of these metastases. Single brain metastases should be treated with surgical resection or stereotactic radiosurgery, though it is unclear at this time if one modality is more effective than the other. Surgical resection is preferred when a pathologic diagnosis is needed, for tumors larger than 3.5 cm, or when immediate tumor mass decompression is required. Stereotactic radiosurgery (SRS) should be applied for single tumors less than 3.5 cm in surgically inaccessible areas and for patients who are not surgical candidates. Small tumors (ie, < 3.5 cm) that cause minimal edema and are surgically accessible may be treated with either surgery or SRS. There is controversy over whether whole brain radiation therapy (WBRT) can be omitted following surgical resection or SRS. Omission of WBRT increases intracranial tumor recurrence; however, this has not been correlated with decreased survival. Clinicians who choose to omit upfront WBRT are obligated to monitor the patient closely for intracranial recurrence, at which time further salvage therapy in the form of surgery, SRS, or WBRT may be considered. Histology is of particular importance when considering WBRT for patients with radioresistant tumors such as melanoma, renal cell carcinoma, or sarcoma. WBRT may be of less clinical benefit in this setting. Chemotherapy has been demonstrated to improve response rates when used as an adjunct to radiation therapy. These improvements in response rates have not been correlated with an improvement in median survival. Noncytotoxic radiosensitizing agents such as motexafin and efaproxiral show promise. Phase III trials to assess the benefit of motexafin in patients with metastatic lung cancer and efaproxiral in patients with metastatic breast cancer are ongoing. Targeted therapies offer promise in achieving therapeutic efficacy while minimizing side effects. Surgical adjuncts such as BCNU (carmustine) wafers and the GliaSite Radiation System (Cytyc Corporation, Marlborough, MA) may be useful in the future in achieving optimal local tumor control.