Characterization of Large Brain Metastases with 18F-Fluciclovine PET/CT Treated with Staged Stereotactic Radiosurgery (SSRS): Phase 1 Proof-of-Concept Interim Analysis

Abstract

Single-session stereotactic radiosurgery (SRS) for large brain metastases (>2cm) results in modest local control. Temporally staged SRS (SSRS), whereby 2 stages of SRS are delivered over a time interval of several weeks, is a novel strategy associated with improved control rates and acceptable radiation necrosis rates. Biomarkers for response are lacking. Here, we report interim results of a phase 1, proof-of-concept study (NCT04689048) to assess the potential clinical utility of amino acid radiotracer 18F-fluciclovine PET/CT as a functional integral biomarker for patients with large brain metastases treated with SSRS. Patients with previously untreated large brain metastases (≥1 lesion; >2cm) underwent a baseline (pre-treatment) 18F-fluciclovine PET/CT and contrast-enhanced treatment planning brain MRI immediately before first SSRS (15 Gy), an interim PET/CT + MRI (4 weeks after the 1st SSRS, immediately prior the 2nd SSRS [15 Gy]), and post-treatment PET/CT + MRI (8 weeks after 2nd SSRS). This interim analysis reviewed the imaging characteristics from static PET images acquired 10-25 minutes after 18F-fluciclovine injection, for the first 7 enrolled patients who completed baseline imaging and 5 who completed the entire treatment course. Seven patients completed baseline imaging and were treated with SSRS for 9 protocol-eligible target lesions, and an additional 25 bystander lesions were treated with SRS. The median age was 72 years and 57% were female. All lesions > 5 mm exhibited baseline increased 18F-fluciclovine uptake compared to the normal contralateral brain. The median baseline target lesion diameters and volumes were 2.16 cm (1.76-3.22 cm) and 4.71cc (2.24-10.21 cc). The median baseline SUVmax, SUVpeak, and SUVmean values were 5.78 (2.16-8.79), 3.33 (0.5-2.72), and 1.75 (1.22-5.16), respectively. The median relative reduction in diameter and volume were both 2% (-13% to 23% and -30% to 60%, respectively) at the interim scans, and at the first follow-up were 30% (-0.2% to 44%) and 43% (-13% to 94%), respectively. Corresponding median relative reduction values for SUVmax, SUVpeak, and SUVmean at interim scans were 20% (-174%-73%), 9% (-99% to 75%), and 14% (-36% to 69%), and at first follow-up 59% (21% to 87%), 41% (-11% to 86%), and 21% (-44% to 79%), respectively. Bystander lesions (< 2 cm) treated with SRS had a median baseline lesion diameter and volume of 0.5 cm (Range: 0.20-1.64 cm) and 0.06 cc (Range: 0.01-1.94 cc). Corresponding median reductions for SUVmax were 5% at interim and 63% at follow-up scans. This proof-of-concept interim study reports baseline 18F-fluciclovine metrics for patients with brain metastases of varying lesion diameters and volumes. Target lesions appear to demonstrate interval reduction in PET metrics after SSRS, more than dimensional measurements alone.