Unfortunately, such metastases are a common occurrence, representing approximately 250,000 cases per year in the US alone.³ Thus, even if only a fraction of these patients are referred for SRS, the management of brain metastases invariably represents a significant fraction of the workload of a radiosurgery practice. Until recently most reports supporting the use of SRS were retrospective case series. This has changed with the publication of randomized trials characterizing the benefits of SRS in the management of newly diagnosed brain oligometastases.

Newly Diagnosed Brain Metastases
Patients with newly diagnosed brain metastases have poor local control after whole-brain radiation (WBRT). Even when intra-cranial disease is limited, neurological death occurs in approximately one-third of patients. These facts underlie the investigation of SRS as an addition to WBRT. In a small trial limited to patients with 2–4 metastases—all ≤25mm in mean diameter— Kondziolka et al. randomized patients to WBRT alone (30Gy in 12 fractions) or WBRT with SRS.⁴ The trial was closed prematurely when the primary endpoint— local control—was achieved after the first 27 patients were enrolled. Local control was 0% at one year in the control arm, well below what is expected. Overall survival was not different between the two arms (median 7.5 months for WBRT and 11.0 months for WBRT plus SRS) and there was no information regarding treatment toxicity or quality of life. In a second small and, as yet, unpublished trial, Chougule et al. randomized patients to three treatment strategies: WBRT (30Gy in 10 fractions), WBRT plus SRS, and SRS alone.⁵ Patients were eligible if they had ≤3 metastases, tumor volume ≤30cc, and a life expectancy of three months. Ninety-six patients received the allocated treatment and were part of the analysis. Approximately half of the patients underwent resection of a large symptomatic lesion prior to randomization. In looking specifically at the issue of adding SRS to WBRT, local control was improved from 62 to 91%, but median overall survival was unchanged (five months for the combination and nine months for WBRT alone). In what is to be the definitive trial of SRS as a focal boost to WBRT, the Radiation Therapy Oncology Group (RTOG) accrued patients in a trial of WBRT (37.5Gy in 15 fractions) versus WBRT followed by SRS (RTOG 95-08).6 From 1999 to 2001, 333 patients were randomized. Eligible patients had 1–3 metastases (the largest ≤4cm), were not surgical candidates, and had a Karnofsky Performance Status score of ≥70. The primary end-point of the trial was overall survival with a planned analysis for patients with a single lesion. Overall, the trial did not find a significant advantage in overall survival (6.5 versus 5.7 months, p=0.13), but did show an improvement in survival for patients with a single lesion (6.5 versus 4.9 months, p=0.04). The less likely a patient is to die from extra-cranial disease, the more he or she is expected to benefit from aggressive central nervous system (CNS)-directed therapy. This was shown in various subgroup analyses. For example, young patients (age <65) having controlled primary tumors and no other metastases had a median survival of 11.6 months with WBRT plus SRS versus 9.6 months for WBRT. The trial also confirmed that SRS can be performed safely, only adding 3% grade III–IV acute and late toxicity.