{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:41:46Z","timestamp":1747190506216,"version":"3.40.5"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Case Reports in Oncological Medicine"],"published-print":{"date-parts":[[2021,7,2]]},"abstract":"<jats:p>The arrival of subsequent generations of tyrosine-kinase inhibitors (TKIs) has significantly broaden the EGFR-mutated lung cancer therapeutic landscape. Results from the FLAURA clinical trial have pushed osimertinib to the first-line treatment for patients with advanced-stage disease, showing outstanding control rates of intracranial metastases, considerably higher than those of the first and second-generation EGFR TKIs. A progressively better knowledge of short and long-term neurocognitive side effects of radiotherapy, as well as the lack of evidence about the benefit of its combination with TKIs, has opened a debate about its indication at diagnosis of intracranial disease, at least before the response to targeted therapy has been evaluated. However, there is a small percentage of primarily resistant cases to osimertinib, mainly due to histologic transformation, acquired EGFR mutations and off-target genetic resistances that lead to a scenery of poor clinical prognosis in which radiotherapy may have a higher relevance for the management of brain metastases. We offer a review of the current recommendations for the management of intracranial metastases in EGFR-mutated NSCLC and the resistance mechanisms to third-generation TKIs, following the report of an unusual clinical case with a rapid progression to osimertinib.<\/jats:p>","DOI":"10.1155\/2021\/5526809","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T16:50:05Z","timestamp":1625331005000},"page":"1-5","source":"Crossref","is-referenced-by-count":0,"title":["Management of Intracranial Metastases in EGFR-Mutated NSCLC: A Review of Literature following an Unusual Case Report"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-2551","authenticated-orcid":true,"given":"V\u00edctor","family":"Albarr\u00e1n","sequence":"first","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9776-9021","authenticated-orcid":true,"given":"Javier","family":"Pozas","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-4233","authenticated-orcid":true,"given":"Juan","family":"Jos\u00e9 Soto","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-016X","authenticated-orcid":true,"given":"Jorge","family":"Esteban","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2413","authenticated-orcid":true,"given":"Elena","family":"Corral","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9351-3184","authenticated-orcid":true,"given":"Yolanda","family":"Lage","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5156-7080","authenticated-orcid":true,"given":"Pablo","family":"Gajate","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5899-6125","authenticated-orcid":true,"given":"Pilar","family":"Garrido","sequence":"additional","affiliation":[{"name":"Thoracic Tumors Unit from Medical Oncology Department, Ram\u00f3n Y Cajal University Hospital, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4163"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70184-X"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709662105"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70086-4"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.3223"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.2100"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S129809"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx820"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.9363"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.3.627"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0264"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14515"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.05.013"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-016-0811-3"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30262-X"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0573-8"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3563"}],"container-title":["Case Reports in Oncological Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/crionm\/2021\/5526809.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/crionm\/2021\/5526809.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/crionm\/2021\/5526809.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T16:50:07Z","timestamp":1625331007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/crionm\/2021\/5526809\/"}},"subtitle":[],"editor":[{"given":"Francesco A.","family":"Mauri","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":18,"alternative-id":["5526809","5526809"],"URL":"https:\/\/doi.org\/10.1155\/2021\/5526809","relation":{},"ISSN":["2090-6714","2090-6706"],"issn-type":[{"type":"electronic","value":"2090-6714"},{"type":"print","value":"2090-6706"}],"subject":[],"published":{"date-parts":[[2021,7,2]]}}}