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

Abstract

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: 29-100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 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.

Figures

Figure 1.

Study selection. FSRT, fractionated stereotactic radiotherapy; LC, local control; Mets, metastases; RT, radiotherapy; SRS, stereotactic radiosurgery.

Figure 2.

Local control for 720 brain metastases treated with fractionated stereotactic radiotherapy. Dotted lines represent 95% confidence intervals.

Figure 3.

Local control for brain metastases treated with fractionated stereotactic radiotherapy. Lesions are split into those that received at least 57.6 Gy10, which was the median biologically effective dose (BED) in the data set, vs other lesions.

Figure 4.

Tumour control probability modelling demonstrating predicted local control at 12 months as function of BED. Dotted lines represent 95% confidence intervals. BED, biologically effective dose.

Figure 5.

Tumour control probability modelling demonstrating predicted local control at 24 months as a function of BED. Dotted lines represent 95% confidence intervals. BED, biologically effective dose.

Figure A1. Scatter plot of 1-year local control vs biologically effective dose for the 10 studies included in this analysis. Larger circles indicate greater sample size.

Figure A2. Scatter plot of 2-year local control vs biologically effective dose for the 10 studies included in this analysis. Larger circles indicate greater sample size.