By Huma Chaudhry, MD, National Institutes of Health
As the most common adult intracranial tumors, brain metastases can occur in 30% of cancer patients. Stereotactic radiosurgery (SRS) has emerged as an alternative to whole brain radiotherapy to better preserve neurocognitive function without compromising survival.1 However, prospective data in patients with a large number of brain metastases treated with SRS is limited.
Chia-Lin Tseng, MD, Sunnybrook Odette Cancer Center, Toronto, Canada, presented neurocognitive outcomes in patients with 5-50 brain metastases treated with stereotactic radiosurgery (SRS) in a phase II single arm clinical trial. To our knowledge, this is the first prospective clinical trial examining neurocognition in patients with such a large burden of brain metastases treated with SRS. The primary endpoint was change in neurocognition at two months in the Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI).
In this prospective study, 56 patients were included with a median of 17 brain metastases (range, 4-50) treated with SRS using Cobalt-60. Of note, prior SRS to 4 or fewer brain metastases was allowed with stable intracranial disease for at least 6 months after the last course of SRS. Patients were treated using the Spatially Partitioned Adaptive RadiosurgEry (SPARE) technique, involving multiday single-fraction treatment to limit hippocampal and normal brain dose.2
Over a third of the patients (22/56, 39%) had 21-50 brain metastases at the time of SRS, demonstrating a high intracranial disease burden. Neurocognitive assessment completion was 52% at 2 months, and as expected, decreased over time to 21% by 9 months. This exemplifies a commonly encountered challenge of long-term data collection in neurocognitive studies of patients with advanced intracranial disease. Median follow-up was 9.4 months (95% CI 9.0-9.7 months).
The results presented by Dr. Tseng demonstrated impressive improved or stable neurocognition. The 2 months HVLT-R Total Recall was improved or stable in 11 (38%) and 15 (52%) patients, respectively. Only 3 (10%) patients demonstrated decline in the HVLT-R Total Recall at 2 months. Clinical Trial Battery Composite (CTB COMP) was analyzed as a secondary outcome measured at 2, 4, 6 and 9 months. Overall, a majority of patients demonstrated stability of CTB COMP, with 16 (55%), 10 (48%), 9 (60%) at 2-, 4-, and 6- months, respectively. Median overall survival was 60.5% (95% CI 45.5-72.6%) at 9 months. In long term survivors, the 9-month CTB COMP was improved, stable or declined in 4 (33%), 6 (50%) and 2 (17%), respectively. This is particularly notable given that the patient population had aggressive disease with a median graded prognostic assessment score of 1.5. These outcomes potentially demonstrate a durable response even beyond 6 months, acknowledging data-collection attrition over time.
When stratified to patients with ≤ 20 vs. > 20 metastases, the difference in cognitive-deterioration-free survival was not statistically significant. Interpretation of this outcome is limited due to the small comparator groups.
Dr. Tseng’s novel prospective work presented at this year’s ASTRO demonstrates favorable neurocognitive outcomes at the primary 2-month endpoint, with a potentially durable response in patients with a high degree of intracranial metastatic disease. To characterize the full extent of intracranial control following SRS, further evaluations are ongoing regarding per-lesion tumor control and salvage therapies. Prospective investigation of the potential neurocognitive advantages of SPARE compared to HA-WBRT in patients with a high (> 20 brain metastases) burden of intracranial disease also remains to be studied.
References
LBA 14, Prospective Neurocognitive Outcomes in Patients with 5 to 50 Brain Metastases Treated with Stereotactic Radiosurgery (SRS): A Phase II Clinical Trial, was presented during SS 33 – Advances in the Treatment of Brain Metastases, at ASTRO's 68th Annual Meeting.
Published on: September 30, 2026
