Octs-09 the Prospective Phase Ii Cog-SRS Trial: An Update on Cognitive-Sparing Stereotactic Radiosurgery for Brain Metastases

Stereotactic radiosurgery (SRS) plans that respect the neural correlates of cognition should result in better post-treatment cognitive outcomes compared to standard plans. The prospective phase II COG-SRS Trial is designed to test this hypothesis. To date, 92 treatment plans that ensure standard tumor coverage but also constrain doses to selected eloquent white matter tracts and the hippocampi have been developed for 70 patients with a total of 158 brain metastases arising from various cancer types. The most common primary malignancies were lung (40%) and breast (26%). Over 90% of plans treated 3 or fewer lesions. 80% of plans successfully met the 0.03cc dose (D0.03) constraint to all white matter tracts, and 95% met the D0.03 constraint to the hippocampi. Cognitive testing of immediate and delayed recall (Hopkins Verbal Learning Test-Revised) and letter and category fluency (Controlled Oral Word Association) is available in 66% (46/70) of patients to date, 76% (35/46) of whom had received systemic therapy and 20% (9/46) surgical resection prior to SRS. Comparing pre- and 3-month post-radiotherapy performance, 52% (24/46) had a significant decline in cognitive performance, defined as a decrease of at least 1 standard deviation in the score on one or more tests. In patients for whom the D0.03 constraint could not be met in white matter tracts, 70% declined significantly. In comparison, only 47% declined when the D0.03 constraint was met. Correlating associations between specific white matter tract doses, volumetric white matter tract changes assessed by serial MRI, and performance on the full battery of neuropsychological testing will be possible when trial data are finalized. These results should help in defining the radiosensitivity of distinct neuroanatomic regions and in guiding future dose-constraint planning protocols, as this new arena of cognitive-sparing SRS continues to be explored.