Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials

Abstract

Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.

Keywords

• brain metastases
• clinical trials
• neoadjuvant radiotherapy
• stereotactic radiosurgery
• stereotactic radiotherapy