Feasibility of Cognitive-Sparing Stereotactic Radiosurgery for Brain Metastases: Initial Report of Phase II COG-SRS Trial

Abstract

Radiotherapy at high doses leads to white matter (WM) and hippocampal injury which can cause cognitive decline. We designed the first, to our knowledge, evidence-based cognitive sparing brain SRS trial for patients with limited brain metastases. In this report we analyze feasibility of cognitive-sparing SRS, utilizing dose constraints for eloquent WM tracts and bilateral hippocampi. This is a single-institution phase II NCI-funded clinical trial (NCT04343157) of cognitive-sparing brain SRS; eloquent regions of interest (ROI) and associated cognitive domains are outlined in Table 1. Patients underwent high-resolution quantitative diffusion and volumetric MRI at baseline and post-SRS follow-up. Comprehensive neurocognitive assessment was performed at baseline and 3 months post-SRS by a neuropsychologist evaluating different neurocognitive domains (Table 1). Clinical processing/workflow was largely automated with robust, validated segmentation tools of eloquent WM tracts and the hippocampi. Single fraction dose constraints to WM tracts were 12 Gy Dmax and 8.4 Gy to hippocampi with 3 and 5 fraction equivalent doses, based on our prior NTCP studies. Patient accrual, follow up imaging and neurocognitive testing is still active. To date, n = 59 patients and 114 lesions have been treated with cognitive-sparing Linac-based SRS on trial. Median age is 63 years. Lung cancer was the most common primary (35.6%), along with breast cancer (23.7%) and melanoma (15.3%). Patients had 1-4 brain metastases; median prescription dose was 24 Gy/1, 27 Gy/3, or 30 Gy/5 depending on target volume. Most patients were treated < 7 business days from MRI. Cognitive endpoints have been collected on 89.5% of patients. Cognitive sparing constraints were met in 79.3% of plans while maintaining standard clinical SRS plan indices and coverage benchmarks. 38.9% of the plans that failed to meet the Dmax constraint kept D0.03cc under constraints. Plans going over constraints had tumors overlying or within 1 mm of eloquent ROIs. Local control for treated lesions at 6 months was 97.9% and 95.7% at 12 months. Distant intracranial control was 68.1% at 6 and 12 months. Median OS was 18 months. Cognitive-sparing SRS treatment planning was successfully implemented for the majority of treated lesions with excellent local control. Mitigation of damage to eloquent structures has potential to further reduce cognitive decline after SRS. Full neurocognitive outcomes will be reported after accrual and testing are complete.