Frameless Fractionated Linear Accelerator-Based Stereotactic Radiotherapy for Brain Metastases: Results of a Single-Arm Phase II Multi-Institutional Clinical Trial

Abstract

Stereotactic radiotherapy (SRT) yields high rates of local control for brain metastases while minimizing neurocognitive side effects. While advanced SRT platforms are widely available in urban centers, rural/suburban patients face geographic and socioeconomic barriers to access SRS. For this reason, we conducted a multi-institutional Phase 2 clinical trial to test the safety and efficacy of 3-5 fraction frameless fractionated stereotactic radiotherapy (FFSRT) for brain metastases in an integrated academic satellite network MATERIALS/METHODS: This IRB-approved Phase 2 trial was conducted for patients ≥18-years-old with 1-4 brain metastases. Brain metastases involving the optic pathway or brainstem were excluded. Gross tumor volume (GTV) was delineated with a volumetric brain MRI and planning target volume (PTV) was GTV + 2 mm margin. Radiation dose was based on GTV size: < 3.0 cm, 27 Gy in 3 fractions, and 3.0-3.9 cm, 30 Gy in 5 fractions. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Of 76 evaluable patients, the median age was 67 years, 56.6% were female, 82.9% were white/Caucasian and 89.6% had an Eastern Cooperative Oncology Group performance status ≤ 2. Most brain metastases were from lung cancer (51.3%) and breast cancer (15.7%). With median follow-up of 10 months, local control was 93%, median survival was 1.8 years (95% confidence interval (CI): 1.5-2.4 years), 1-year OS was 73.8% (95% CI: 0.59-0.84), and 2-year OS was 31% (95% CI: 0.12-0.52). There were no CTCAE Grade ≥ 3 protocol-related adverse events. Outcomes of this trial compare favorably with contemporary SRT trials for brain metastases. FFSRT may provide opportunities to expand SRS access for underserved populations across the MDACC enterprise and in future clinical trials for brain metastases.