A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors

The purpose of this prospective study is to evaluate the efficacy and limitations of two-session Gamma Knife radiosurgery (GKS) alone for large metastatic brain tumors. Inclusion criteria were as follows: (i) patients with large metastatic brain tumors (volume >15 cm(3) in the supratentorial region or >10 cm(3) in the infratentorial region), and (ii) tumors not causing clinical signs of impending cerebral herniation. Twenty-eight lesions in 27 consecutive patients (18 men and 9 women, age range 32 to 88 years, median age 65 years) were included in this study. The radiosurgical protocol was as follows: 20–30 Gy given in two fractions 3–4 weeks apart. The local tumor control rate and the overall survival rate were calculated by using the Kaplan–Meier method. Median tumor volumes were 17.8 cm(3) at first GKS and 9.7 cm(3) at second GKS. Median follow-up time was 8.9 months. The local control rate was 85 % at 6 months and 61 % at 12 months. The overall survival rate after GKS was 63 % at 6 months and 45 % at 12 months. The 1-year rate of prevention of neurological death was maintained at 78 %. Mean Karnofsky performance status (KPS) improved from 61 [95 % confidence interval (CI), 57–71] at first GKS to 80 (95 % CI, 74–85) at second GKS; the best follow-up mean KPS was 85 (95 % CI, 78–91) (p < 0.001). Local tumor recurrence necessitated craniotomy in two patients and repeat GKS in three patients. Seventeen patients died, and the causes of death were as follows: 3 from local progression, 2 from meningeal carcinomatosis, and 12 from progression of the primary tumor. Delayed symptomatic perilesional edema developed in one patient and eventually resolved with conservative treatment. Two-session GKS for large brain metastases appears to be an effective treatment in terms of both local tumor control and neurological palliation with minimal treatment-related morbidity. These data suggest that two-session GKS could be used as an alternative to surgical resection of large tumors in patients with significant comorbidity and/or at an advanced age. The optimum regimen for dose and fraction schedule remains to be established.