{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:17:35Z","timestamp":1788380255999,"version":"build-2803163510"},"reference-count":27,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National University Health System Medical Research Application (HREF) - Cancer Fund","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100013741","name":"The Royal Australian New Zealand College of Radiologists","doi-asserted-by":"crossref","award":["2020\/RANZCR\/026"],"award-info":[{"award-number":["2020\/RANZCR\/026"]}],"id":[{"id":"10.13039\/100013741","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011105","name":"National University Cancer Institute, Singapore","doi-asserted-by":"publisher","award":["(gift from Mr Sajiv Misra via Phoenix Advisers Pte"],"award-info":[{"award-number":["(gift from Mr Sajiv Misra via Phoenix Advisers Pte"]}],"id":[{"id":"10.13039\/501100011105","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Trans Tasman Radiation Oncology Group","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["ESR-17-12872"],"award-info":[{"award-number":["ESR-17-12872"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["ESR-17-13033"],"award-info":[{"award-number":["ESR-17-13033"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011744","name":"National University Health System","doi-asserted-by":"publisher","award":["NUHSRO\/2019\/053\/RO5+5\/Seed-Mar\/06"],"award-info":[{"award-number":["NUHSRO\/2019\/053\/RO5+5\/Seed-Mar\/06"]}],"id":[{"id":"10.13039\/501100011744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011744","name":"National University Health System","doi-asserted-by":"crossref","award":["NUHSRO\/2019\/053\/RO5"],"award-info":[{"award-number":["NUHSRO\/2019\/053\/RO5"]}],"id":[{"id":"10.13039\/501100011744","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,6,10]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (\n                      <jats:italic>EGFR<\/jats:italic>\n                      ) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Randomised controlled trials will be eligible if they include participants with BM arising from\n                      <jats:italic>EGFR-<\/jats:italic>\n                      mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO\u2019s International Clinical Trials Registry Platform\u2019s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Approved by each trial\u2019s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Prospero registration<\/jats:title>\n                    <jats:p>CRD42022330532.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-078335","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T10:41:22Z","timestamp":1720176082000},"page":"e078335","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET 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