Comparison of Staged Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy in Patients with Brain Metastases > 2 cm without Prior Whole Brain Radiotherapy: A Systematic Review and Meta-Analysis

Abstract

Objective: To compare fractionated stereotactic radiotherapy (FSRT) with staged stereotactic radiosurgery (SSRS) in patients with brain metastases >2 cm without prior whole brain radiotherapy.

Methods: In this systematic review and meta-analysis, PubMed, Scopus, Web of Science, Embase, and Cochrane were searched to include studies that evaluated FSRT and/or SSRS for brain metastases >2 cm or 4 cm³ in adult patients with a known primary malignancy and no prior history of whole brain radiotherapy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and an indirect random-effect meta-analyses was conducted to compare treatment outcomes between the two modalities.

Results: A total of 10 studies were included, comprising 612 (778 metastases) and 250 patients (265 metastases) in the SSRS and FSRT groups, respectively. The SSRS group had significantly older patients (66.6 ± 17.51 years vs. 62.37 ± 37.89 years; P = 0.029) with lower rate of control of primary disease (11.59% vs. 78.7%, P < 0.00001), and more patients with Karnofsky performance status ≥70 at baseline (92.81% vs. 88.56%; P = 0.045). FSRT was associated with a statistically nonsignificant but clinically important lower 12-month overall survival (44.75% [95% confidence interval [CI]: 30.48%-59.95%] vs. 53.25% [95%CI: 45.15%-61.19%], P = 0.1615) and higher rate of salvage radiotherapy (18.18% [95%CI: 8.75%-34%] vs. 12.27% [95%CI: 5.98%-23.53%], P = 0.0841). Both groups had comparable rates of local tumor control, mortality, tumor progression, recurrence, neurological death, and 6-month overall survival.

Conclusions: SSRS and FSRT were found to be comparable for treating brain metastases >2 cm not previously irradiated. Given the paucity of such studies, trials directly comparing the two treatment strategies are warranted to support these findings.

Keywords: Brain metastases; Fractionated stereotactic radiotherapy; Neuro-Oncology; Staged stereotactic radiosurgery; Stereotactic radiosurgery.