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Surgery, whole brain radiation therapy (WBRT), or stereotactic radiosurgery (SRS), have historically been the main focal treatments for BM. However, the introduction of innovative targeted- and immune-based therapies is progressively changing the paradigm of BM treatment, resulting in an increase in clinical trials investigating new therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using ClinicalTrials.gov, the largest clinical trial registry with over 400,000 registered trials, we performed an analysis of phase II and phase III ongoing trials evaluating different systemic therapies, radiotherapy (RT), and surgery given alone or in combination in patients with BM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One hundred sixty-eight trials, 133 phase II and 35 phase III; the largest part having primarily the curative treatment of patients with BM from lung cancer, breast cancer and melanoma, were selected. One hundred sixty-three trials used systemic therapies. One hundred thirteen used tyrosine kinase inhibitors, more frequently Osimertinib, Icotinib and Pyrotinib, 50 used monoclonal antibodies, more frequently Trastuzumab, Pembrolizumab, Nivolumab, 20 used conventional chemotherapies whilst no oncological active drugs were used in 6 trials. Ninety-six trials include RT; 54 as exclusive treatment and 42 in combination with systemic therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Systemic targeted- and\/or immune-based therapies, combined or not with RT, are increasingly used in the routine of BM treatment. SRS is progressively replacing WBRT. All these trials intend to address multiple questions on the management of patients with BMs, including the recommended upfront treatment for different cancer histologies and the optimal timing between systemic therapies and radiation regarding brain control and neurocognitive outcome and quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13014-023-02243-2","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T04:13:54Z","timestamp":1680668034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov"],"prefix":"10.1186","volume":"18","author":[{"given":"Paolo","family":"Tini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Giraffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Bucelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Niyazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Belka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Minniti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"2243_CR1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.nec.2020.06.001","volume":"31","author":"P Sacks","year":"2020","unstructured":"Sacks P, Rahman M. 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