Stereotactic radiosurgery for 1–10 brain metastases to avoid whole-brain radiotherapy: Results of the CYBER-SPACE randomized phase 2 trial

Abstract: Background
Stereotactic radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity, and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1–10 BM.

Methods
Patients with 1–10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of >10 new BM, leptomeningeal disease, or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life.

Results
A total of 202 patients were randomized; SPACE n = 99, MPRAGE n = 103. Twelve-month WBRTi-free survival was 77.1% (95% CI: 69.5%–83.1%) overall, 78.5% (95% CI: 66.7%–86.5%) for SPACE, and 76.0% (95% CI: 65.2%–83.9%) for MPRAGE (hazard ratio [HR] = 0.84, 95% CI: 0.43–1.63, P = .590). Patients with 5–10 BM had shorter WBRTi-free survival (HR = 3.13, 95% CI: 1.53–6.40, P = .002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR = 1.10, 95% CI: 0.78–1.56, P = .585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status >80% (HR = 0.51, 95% CI: 0.33–0.77, P = .002) and concurrent immunotherapy (HR = 0.34, 95% CI: 0.23–0.52, P < .001).

Conclusions
The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1–10 BM

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Neuro-Oncology. - 27, 2 (2025) , 479-491, ISSN: 1523-5866

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2024
• Creator: El-Shafie, Rami ; Bernhardt, Denise ; Welzel, Thomas ; Schiele, Annabella ; Schmitt, Daniela ; Thalmann, Paul ; Erdem, Sinem ; Paul, Angela ; Höne, Simon ; Uzun-Lang, Kristin ; König, Laila ; Weykamp, Fabian ; Adeberg, Sebastian ; Hommertgen, Adriane ; Jäkel, Cornelia ; Bozorgmehr, Farastuk ; Nestle, Ursula ; Thomas, Michael ; Sander, Anja ; Kieser, Meinhard ; Debus, Jürgen ; Rieken, Stefan

Further information

• DOI: 10.1093/neuonc/noae201
• URN: urn:nbn:de:bsz:25-freidok-2586583
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:35 AM CEST