General Considerations
Available treatment options for brain metastasis include focal (i.e. surgery and radiosurgery) and non-focal (whole-brain radiotherapy and chemotherapy) treatment modalities. In spite of numerous randomised trials, the optimal timing and patient selection for each of these treatment modalities remains contentious. This controversy seems to derive from two main issues: the first is related to the extreme heterogeneity of patients with brain metastasis, who can differ considerably in terms of prognostic characteristics such as primary cancer type, systemic disease control, brain metastasis location, number of lesions, age, performance status, and presence of cognitive or other neurologic impairment. This renders extremely difficult the task of extrapolating generic results derived from clinical trials to an individual patient. To address this issue, the Radiation Therapy Oncology Group (RTOG) proposed a classification based on a recursive partitioning analysis (RPA) of a large population of patients with brain metastasis in an effort to homogenise patient populations for clinical trials and facilitate treatment decisions. For this classification, patients are divided into three classes based on Karnofsky performance status (KPS), age and extent of systemic disease. The resulting stratification has prognostic value and has been validated in a variety of primary cancer types. Although the RPA classification may help provide general guidelines, it is not perfect, particularly because it does not take histology into consideration.

A second major source of controversy in the management of brain metastasis has been the lack of trials adequately designed and powered to investigate questions related to the balance between successful tumour control and long-term treatment-related neurocognitive impairment. Radiotherapy is particularly associated with an increased risk of neurotoxicity; however, it has been difficult to ascertain the magnitude of this problem, especially because it is difficult to differentiate tumour burden on neurologic function from neurotoxic effects. Moreover, assessment of neurotoxicity depends on long-term neuropsychological follow-up, which has been difficult to incorporate into large prospective studies. Results of available clinical trials and details pertaining to each treatment modality are reviewed below.

Whole-bra in Radiation Therapy
Whole-brain radiation therapy (WBRT) has historically been the most important modality of treatment for brain metastases. Phase III trials have demonstrated that WBRT achieves radiographic responses and improves neurologic function in approximately 50% of patients; median survival increases to 4 6 months. Central nervous system (CNS) disease is the cause of death in approximately half of these patients, while the other half will die from systemic disease progression.