Stereotactic radiosurgery for 1–10 brain metastases to avoid whole-brain radiotherapy: Results of the CYBER-SPACE randomized phase 2 trial
Rami A. El Shafie, Denise Bernhardt, Thomas Welzel, Annabella Schiele, Daniela Schmitt, Paul Thalmann, Sinem Erdem, Angela Paul, Simon Höne, Kristin Lang, Laila König, Fabian Weykamp, Sebastian Adeberg, Adriane Lentz-Hommertgen, Cornelia Jäkel, Farastuk Bozorgmehr, Ursula Nestle, Michael Thomas, Anja Sander, Meinhard Kieser, Jürgen Debus, Stefan Rieken
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.