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

Paolo Palmisciano; Gianluca Ferini; Ramlah Khan; Othman Bin-Alamer; Giuseppe E Umana; Kenny Yu; Aaron A Cohen-Gadol; Tarek Y El Ahmadieh; Ali S Haider

doi:10.3390/cancers14174328

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

Cancers (Basel). 2022 Sep 4;14(17):4328. doi: 10.3390/cancers14174328.

Authors

Paolo Palmisciano¹, Gianluca Ferini², Ramlah Khan³, Othman Bin-Alamer⁴, Giuseppe E Umana⁵, Kenny Yu⁶, Aaron A Cohen-Gadol⁷, Tarek Y El Ahmadieh⁸, Ali S Haider⁹

Affiliations

¹ Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA.
² Department of Radiation Oncology, REM Radioterapia srl, 95029 Viagrande, Italy.
³ College of Medicine, Texas A&M University, College Station, TX 77843, USA.
⁴ Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
⁵ Department of Neurosurgery, Trauma Center, Gamma Knife Center, Cannizzaro Hospital, 95126 Catania, Italy.
⁶ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁷ Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46290, USA.
⁸ Department of Neurosurgery, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
⁹ Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

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.

Publication types

Review

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States