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Dose-response relationships for radiotherapy of brain metastases: role of intermediate-dose stereotactic radiosurgery plus whole-brain radiotherapy.

The effects of intermediate-dose radiotherapy consisting of whole-brain radiotherapy (WBRT, 10 fractions of 3 Gy) plus stereotactic radiosurgery (SRS) were studied prospectively. Twenty-five adult patients with 31 brain metastases received WBRT plus linear accelerator (LINAC)-based single dose SRS with fixed treatment parameters (10 Gy at the isocenter, target volume enclosed by the 90% isodose). Median age was 63 years, median Karnofsky performance status 80%, and median diameter of brain metastases 2.4 cm. Fifteen patients had non-small-cell lung cancer. Because of some early deaths, only 26 lesions could be evaluated for response. We observed 1 complete and 15 partial remissions. Median time to progression inside or outside the SRS volume was 4.5 months. Actuarial local control of SRS-treated lesions was 61% at 1 year. At that time, only 37% of patients were free from new lesions outside the SRS volume. Median survival and cause-specific survival were 2.3 and 4.5 months, respectively (1-year survival rate 8% and 21%). Ten patients died of progressive brain metastases, 13 from extracranial disease progression (unknown cause of death in 2 cases). Comparable to SRS studies with higher doses, the majority of brain failures occurred outside the SRS volume and more patients died of extracranial progression than of uncontrolled brain metastases. Failure to improve survival can be explained by the high percentage of patients with extracranial metastases (52%). However, the present results appear less favorable than those of previous studies of SRS with 15 Gy to 16 Gy (1-year actuarial local control rates of 66-89%). Therefore, we recommend SRS with 15 Gy to 16 Gy for patients whose favorable prognostic factors justify a boost after WBRT.