2588 - Neurocognition Following Repeated Stereotactic Radiosurgery for 1-10 Brain Metastases: Results of the CYBER-SPACE Randomized Phase II Trial
Presenter(s)
R. El Shafie1,2, D. Bernhardt2,3, T. Welzel2, A. Schiele2, D. Schmitt1,2, P. Thalmann4, S. Erdem2, A. Paul2, T. Eichkorn2, K. Lang2, F. Weykamp2, S. Adeberg2,5, A. Lentz-Hommertgen2, C. Jaekel2, F. Bozorgmehr6,7, M. Thomas6,7, M. Kieser4, J. Debus2, and S. Rieken1,2; 1University Medical Center Göttingen (UMG), Dept. of Radiation Oncology, Göttingen, Germany, 2Heidelberg University Hospital, Dept. of Radiation Oncology, Heidelberg, Germany, 3Department of Radiation Oncology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany, 4Heidelberg University Hospital, Institute of Medical Biometry, Heidelberg, Germany, 5University Medical Center of Gießen and Marburg (UKGM), Dept. of Radiation Oncology, Marburg, Germany, 6National Center for Tumor diseases (NCT), Heidelberg, Germany, 7Department of Thoracic Oncology, Thoraxklinik and National Center for Tumor diseases (NCT) Heidelberg, Heidelberg University Hospital, Heidelberg, Germany
Purpose/Objective(s): The CYBER-SPACE randomized phase II trial evaluated stereotactic radiosurgery (SRS) for 1-10 brain metastases (BM), with regular MRI follow-up and repeated SRS for new lesions, aiming to avoid or delay whole-brain radiotherapy (WBRT). SPACE MRI sequence (sampling perfection with application optimized contrasts using different flip angle evolution) was randomized against MPRAGE (magnetization-prepared rapid gradient-echo) for lesion detection. Neurocognitive function was a pre-specified secondary endpoint.
Materials/Methods: Neurocognitive testing included the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall (TR) and delayed recall (DR), as well as a comprehensive tablet-based test battery by CANTAB (Cambridge Neuropsychological Test Automated Battery), covering multiple domains of episodic and working memory, executive function, psychomotor speed, and attention. All assessments were performed at baseline, 6-8 weeks after treatment and three-monthly afterwards for at least 12 months. Primary outcome of this analysis was time to neurocognitive failure (NF), defined as the first failure in any of the performed neurocognitive tests by either reliable change index criteria or standardized Z-score analysis.
Results: 202 patients were randomized; SPACE n = 99, MPRAGE n = 103. Most common histologies were non-small cell lung cancer (63%), melanoma (16%) and breast cancer (10%). Median number of treated lesions was 4 [Q1-Q3: 2-8] with a median maximum diameter of 11 mm [Q1-Q3: 6-17]. Median follow-up was 23.2 [Q1-Q3: 8.0-24.0] months. Rate of WBRT indication (WBRTi) across both arms was 21.7% at 24 months, as reported previously. In the overall study population, 37 patients (19.3%) had experienced NF at 12 months from baseline, and 39 patients (20.4%) at 24 months. By competing risk analysis adjusted for death or WBRTi, freedom from NF at 12 months was 71.2% (95%-CI: 62.2%; 78.4%). Median time to NF was not reached [Q1-Q3: 9.1 months - NR]. Allocation to the treatment arms (SPACE vs. MPRAGE) did not significantly influence time to NF (HR 1.71 [95%-CI 0.90; 3.23], p=0.101). Treatment-related factors including number of BM at baseline, total number of treated BM, number of SRS courses, largest BM diameter, and concomitant systemic therapy were not significantly associated with time to NF in competing risk-adjusted Cox regression (p > 0.5 for each).
Conclusion: Repeated SRS for multiple BM can avoid WBRT and effectively preserves neurocognition, achieving long-term neurocognitive stability in 4 out of 5 patients. Treatment-related factors did not influence the individual risk of NF. These results support the use of repeated SRS for multiple BM instead of WBRT.