Journal of Neuro-Oncology 61: 73–80, 2003. © 2003 Kluwer Academic Publishers. Printed in the Netherlands. Clinical Study Properly selected patients with multiple brain metastases may benefit from aggressive treatment of their intracranial disease Bruce E. Pollock 1 , Paul D. Brown 2 , Robert L. Foote 2 , Scott L. Stafford 2 and Paula J. Schomberg 2 1 Department of Neurological Surgery, 2 Division of Radiation Oncology, Mayo Clinic and Foundation, Rochester, MN, USA Key words: brain tumor, metastasis, radiosurgery, surgery Summary To determine whether properly selected patients with multiple brain metastases benefit from aggressive treatment of their intracranial disease, we reviewed 52 patients having stereotactic radiosurgery (SRS), tumor resection, or both between April 1997 and March 2000. Tumor histology included lung (n = 18, 35%), breast (n = 11, 21%), renal (n = 6, 12%), melanoma (n = 6, 12%), and other (n = 11, 21%). The median patient age was 58 years, the median Karnofsky performance status (KPS) was 90, and the median number of tumors was three. Twenty patients (39%) had progressed after prior radiation therapy. Treatment included multiple craniotomies and tumor resection (n = 5, 10%), radiosurgery (n = 31, 60%), or resection and radiosurgery (n=16, 30%). Median survival was 15.5 months. The one- and two-year actuarial survivals were 63% and 27%, respectively. Multivariate analysis found radiation therapy oncology group recursive partitioning analysis (RTOG RPA) Class (1 vs. 2/3) correlated with improved survival (Relative risk = 2.60, 95% CI 1.13–5.97, p = 0.03). Class 1 patients (KPS ≥ 70, age < 65 years, and controlled primary with no extracranial metastases) survived a median of 19 months whereas Class 3 patients (KPS < 70) survived 8 months. Class 2 patients (all other patients) survived a median of 13 months. Thirty-five patients (67%) had intracranial progression at a median of 8.0 months. Intracranial progression was local (n = 6), distant (n = 23), or local and distant (n = 6); 26 patients with intracranial progression underwent additional brain tumor treatments. Multivariate analysis found patients with radiosensitive tumors (lung, breast, other) had fewer intracranial recurrences compared to patients with radio-resistant tumors (melanoma, renal, sarcoma) (Relative risk = 2.43, 95% CI 1.13–5.10, p = 0.02). The length of survival in our series is quite comparable to historical reports on the management of brain metastasis patients, and supports aggressive intervention for RTOG RPA Class 1 patients and Class 2 patients with controlled primary disease who have a limited number of brain metastases. Introduction Metastatic brain disease is a common oncologic prob- lem affecting an estimated 100,000–170,000 people in the United States each year [1,2]. Despite significant advances in the detection and treatment of brain metas- tases, the prognosis for this patient group remains poor with median survival rates reported between 2.9 and 3.4 months [3,4]. However, within this patient popula- tion subgroups appear to exist that are associated with improved survival. Gaspar et al. [5] used recursive par- titioning analysis (RPA) to evaluate patient survival from three consecutive radiation therapy oncology group (RTOG) trials involving more than 1200 patients. Eighteen pre-treatment and three treatment-related variables were analyzed and ranked according to prog- nostic significance. Class 1 patients were <65 years of age, had a Karnofsky performance status (KPS) ≥70, and a controlled primary tumor with the brain as the only site of metastases. Class 3 patients had a KPS <70. All other patients were Class 2. The median sur- vival of Class 1 patients was 7.1 months, compared to 4.2 and 2.3 months for Class 2 and 3 patients, respec- tively. Unfortunately, only 3–20% of patients with brain metastases are Class 1 by the RTOG RPA criteria [3,4]. Bindal et al. [6] reviewed 56 patients with mul- tiple brain metastases undergoing surgical resection and found the median survival time (14 months) for