{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:25:14Z","timestamp":1792214714507,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T00:00:00Z","timestamp":1727481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u201310 BM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with 1\u201310 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 &amp;gt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 202 patients were randomized; SPACE n\u2005=\u200599, MPRAGE n\u2005=\u2005103. Twelve-month WBRTi-free survival was 77.1% (95% CI: 69.5%\u201383.1%) overall, 78.5% (95% CI: 66.7%\u201386.5%) for SPACE, and 76.0% (95% CI: 65.2%\u201383.9%) for MPRAGE (hazard ratio [HR]\u2005=\u20050.84, 95% CI: 0.43\u20131.63, P\u2005=\u2005.590). Patients with 5\u201310 BM had shorter WBRTi-free survival (HR\u2005=\u20053.13, 95% CI: 1.53\u20136.40, P\u2005=\u2005.002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR\u2005=\u20051.10, 95% CI: 0.78\u20131.56, P\u2005=\u2005.585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status &amp;gt;80% (HR\u2005=\u20050.51, 95% CI: 0.33\u20130.77, P\u2005=\u2005.002) and concurrent immunotherapy (HR\u2005=\u20050.34, 95% CI: 0.23\u20130.52, P\u2005&amp;lt;\u2005.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u201310 BM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noae201","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T15:20:28Z","timestamp":1727104828000},"page":"479-491","source":"Crossref","is-referenced-by-count":22,"title":["Stereotactic radiosurgery for 1\u201310 brain metastases to avoid whole-brain radiotherapy: Results of the CYBER-SPACE randomized phase 2 trial"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-7882","authenticated-orcid":false,"given":"Rami A","family":"El Shafie","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]},{"name":"Department of Radiation Oncology, University Medical Center G\u00f6ttingen , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-9097","authenticated-orcid":false,"given":"Denise","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]},{"name":"Department of Radiation Oncology, School of Medicine and Klinikum rechts der Isar, Technical University of Munich (TUM) , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Welzel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University 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,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]},{"name":"Department of Radiation Oncology, University Medical Center G\u00f6ttingen , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Thalmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry, University of Heidelberg , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinem","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"H\u00f6ne","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriane","family":"Lentz-Hommertgen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"J\u00e4kel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Heidelberg , Heidelberg ,","place":["Germany"]},{"name":"Heidelberg Institute of Radiation Oncology (HIRO) , Heidelberg ,","place":["Germany"]},{"name":"National Center for Tumor Diseases (NCT) , Heidelberg 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