Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm.

Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS and may lower the risk of radiation necrosis (RN) and leptomeningeal disease (LMD) recurrence. The study goal was to report the efficacy and toxicity of preoperative SRS in an expanded patient cohort with longer follow-up period relative to prior reports. The records for patients with brain metastases treated with preoperative SRS and planned resection were reviewed. Patients with classically radiosensitive tumors, planned adjuvant whole brain radiotherapy, or no cranial imaging at least 1 month after surgery were excluded. Preoperative SRS dose was based on lesion size and was reduced approximately 10-20% from standard dosing. Surgery generally followed within 48 hours. The study cohort consisted of 117 patients with 125 lesions treated with single-fraction preoperative SRS and planned resection. Of the 117 patients, 24 patients were enrolled in an initial prospective trial; the remaining 93 cases were consecutively treated patients who were retrospectively reviewed. Most patients had a single brain metastasis (70.1%); 42.7% had non-small cell lung cancer, 18.8% had breast cancer, 15.4% had melanoma, and 11.1% had renal cell carcinoma. Gross total resection was performed in 95.2% of lesions. The median time from SRS to surgery was 2 days, the median SRS dose was 15 Gy, and the median gross tumor volume was 8.3 cm3. Event cumulative incidence at 2 years was as follows: cavity local recurrence (LR), 25.1%; distant brain failure, 60.2%; LMD, 4.3%; and symptomatic RN, 4.8%. The median overall survival (OS) and 2-year OS rate were 17.2 months and 36.7%, respectively. Subtotal resection (STR, n = 6) was significantly associated with increased risk of cavity LR (hazard ratio [HR] 6.67, p = 0.008) and worsened OS (HR 2.63, p = 0.05) in multivariable analyses. This expanded and updated analysis confirms that single-fraction preoperative SRS confers excellent cavity local control with very low risk of RN or LMD. Preoperative SRS has several potential advantages compared to postoperative SRS, including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilization of tumor cells prior to spillage at the time of surgery. Subtotal resection, though infrequent, is associated with significantly worse cavity LR and OS. Based on these results, a randomized trial of preoperative versus postoperative SRS is being designed.