{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T13:10:02Z","timestamp":1783170602641,"version":"3.54.6"},"reference-count":45,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non\u2013small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET\/CT, or MR spectroscopy, and consensus by local clinical providers was required.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58\u201373 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18\u201320 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p &lt; 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p &lt; 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p &lt; 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving \u2265 12 Gy of radiation (V12Gy) \u2265 10 cm<jats:sup>3<\/jats:sup> (OR 2.78, p &lt; 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.<\/jats:p>\n<\/jats:sec>","DOI":"10.3171\/2022.7.jns22752","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T14:45:42Z","timestamp":1663339542000},"page":"1178-1187","source":"Crossref","is-referenced-by-count":19,"title":["Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients"],"prefix":"10.3171","volume":"138","author":[{"given":"Eric J.","family":"Lehrer","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manmeet S.","family":"Ahluwalia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Miami Cancer Institute, Miami, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gurewitz","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Departments of Radiation Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Kondziolka","sequence":"additional","affiliation":[{"name":"Neurosurgery, NYU Langone Medical Center, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Niranjan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhishuo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Dade","family":"Lunsford","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareem R.","family":"Fakhoury","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Colorado, Aurora, Colorado;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad G.","family":"Rusthoven","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Colorado, Aurora, Colorado;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Trudel","sequence":"additional","affiliation":[{"name":"Medicine, Universit\u00e9 de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Qu\u00e9bec, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Malouff","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Ruiz-Garcia","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Bonney","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Hwang","sequence":"additional","affiliation":[{"name":"Radiation Oncology, University of Southern California, Los Angeles, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Zada","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, Alberta, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Deibert","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Emory University, Atlanta, Georgia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Picozzi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, IRCCS Humanitas Research Hospital, Rozzano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Franzini","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, IRCCS Humanitas Research Hospital, Rozzano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Attuati","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, IRCCS Humanitas Research Hospital, Rozzano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul N.","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju R.","family":"Raval","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Ohio State University Wexner Medical Center, Columbus, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chia","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Che","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Trifiletti","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"1","key":"b1","series-title":"Neurooncol Adv","first-page":"vdaa041","article-title":"Epidemiology of synchronous brain metastases","volume":"2","author":"Singh R","year":"2020","unstructured":"Singh R, Stoltzfus KC, Chen H,  Epidemiology of synchronous brain metastases. 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