LBA 14 - Prospective Neurocognitive Outcomes in Patients with 5 to 50 Brain Metastases Treated with Stereotactic Radiosurgery (SRS): A Phase II Clinical Trial
Presenter(s)
C. L. Tseng1, H. Soliman1, J. Detsky1, H. Chen1, C. Heyn2, P. Maralani2, N. Lipsman3, S. Das4, J. Perry5, M. E. Ruschin1, J. S. Wefel6,7, and A. Sahgal1; 1Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 3Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 4Division of Neurosurgery, St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada, 5Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 6Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Stereotactic radiosurgery (SRS) is the standard of care for patients with up to 4 brain metastases. Recent randomized data in patients with 5 to 20 brain metastases support improved local control, fewer symptoms, and less functional interference in those treated with SRS vs. hippocampal avoidance whole brain radiotherapy (HA-WBRT). This phase 2 single-arm study aimed to prospectively assess change in neurocognition in patients with 5 to 30 brain metastases at the time of enrolment treated with SRS using Cobalt-60 based radiotherapy, applying the Spatially Partitioned Adaptive RadiosurgEry technique (SPARE).
Materials/Methods: Eligible adult patients with 5 to 30 brain metastases identified on a screening MRI within 30 days prior to study entry were enrolled, with allowance of up to 50 metastases on the SRS treatment planning MRI. Prior SRS to 4 or fewer brain metastases was allowed if the intracranial disease was stable for at least 6 months after last course of SRS. Germ cell malignancies, small cell histologies and leptomeningeal metastases were excluded from study participation. The SPARE approach has been previously described. The primary endpoint was change in neurocognitive function at 2 months in the Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall using the Reliable Change Index (RCI). Secondary endpoints included the Clinical Trial Battery Composite (CTB COMP) at the 2-, 4-, 6-, and 9-month follow-up assessment post-SRS, and overall survival (OS). Time to neurocognitive failure was summarized by cumulative incidence that accounted for death as a competing risk, and OS summarized by Kaplan-Meier.
Results: Of 64 patients accrued between December 2020 through April 2024, 56 patients underwent study treatment, 22 (39%) of whom had 21-50 brain metastases at the time of SRS. The mean age was 58.6 (SD, 10.2 years); 20 (36%) were male; median graded prognostic assessment score was 1.5 (IQR, 1.0-2.5); median number of brain metastases was 17 (range, 4-50), and 29 (52%), 21 (38%), 15 (27%), and 12 (21%) patients completed neurocognitive assessment at the 2-, 4-, 6- and 9-month follow-up. Median follow-up was 9.4 months (95% CI 8.5-9.7 months). At 2 months, the HVLT-R Total Recall was improved, stable, and declined in 11 (38%), 15 (52%), and 3 (10%) patients, respectively. At the 2-, 4-, 6- and 9-month assessment, the CTB COMP was improved in 9 (31%), 6 (29%), 2 (13%), 4 (33%), stable in 16 (55%), 10 (48%), 9 (60%), 6 (50%), and declined in 4 (14%), 5 (24%), 4 (27%), and 2 (17%) patients, respectively. Median time to failure in any neurocognitive test was 3.6 months. Overall survival was 60.6% (95% CI 45.5-72.7%) at 9 months.
Conclusion: In patients with 5 to 50 brain metastases, SRS alone resulted in favorable neurocognitive outcomes at the primary 2-month endpoint. Further analysis of outcomes stratified according to those with = 20 vs. > 20 metastases is ongoing and will be presented.