Low-dose Gamma Knife radiosurgery plus whole-brain radiation therapy for patients with 5 or more brain metastases with or without meningeal dissemination

Akifumi Miyakawa, Yuta Shibamoto, Shinya Takemoto, Tatsuo Hirai, Toru Serizawa

Radiosurgery plus whole-brain radiotherapy (WBRT) has been reported to be useful for patients with ≤ 4 brain metastases (BM), but we hypothesized that similar treatment may be applicable to patients with ≥ 5 BM with or without meningeal dissemination. The purpose of this study was to evaluate the efficacy and toxicity of low-dose Gamma Knife (GK) followed by WBRT for patients with advanced BM. Major eligibility criteria for this phase II study were: (1) ≥ 5 BM with or without meningeal dissemination and (2) the largest tumor diameter ≤ 4 cm. During 2013-2016, 40 patients (13 men and 27 women) entered the study. Nineteen had meningeal dissemination. The GK dose was 12 Gy at the periphery when the longest diameter was 3-4 cm and 14 Gy when it was < 3 cm. The WBRT dose to the isocenter was 30 Gy in 10 fractions, or 37.5 Gy in 15 fractions for two patients, with an expected survival of > 12 months. The median number of target BM was 17.5. After GK plus WBRT for 40 patients, 31 did not develop further intracranial recurrence until death or last follow-up, whereas 9 developed recurrence. With a follow-up period up to 24 months, the overall survival rate was 36% at 12 months and median survival time was 8 months. The cumulative incidence of intracranial recurrence was 25% at 12 months. Toxicity was considered acceptable. Treatment with low-dose GK followed by WBRT for advanced-stage BM appeared to contribute to local control.