Fractionated stereotactic radiation therapy for brain metastases: A systematic review with tumour control probability modelling

Objective: Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen. Methods: We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan-Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT. Results: 10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3-12 fractions (BED range: 29-100Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR50.77 per increase of 10Gy10, p50.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively. Conclusion: FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose- response relationship that should be explored in prospective trials. Advances in knowledge: This review identified a dose- response relationship for LC in patients treated with FSRT for brain metastases.