{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:19:06Z","timestamp":1778271546610,"version":"3.51.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"The Nanjing Technology Development Special Fund","award":["ZKX24052"],"award-info":[{"award-number":["ZKX24052"]}]},{"name":"The CSCO Fund\u2014EGFR Mutant Non\u2013Small Cell Lung Cancer Research Fund","award":["Y-2024AZ(EGFR)MS-0101"],"award-info":[{"award-number":["Y-2024AZ(EGFR)MS-0101"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1007\/s11060-026-05544-0","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:53:09Z","timestamp":1774529589000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvage dacomitinib plus intraventricular pemetrexed for leptomeningeal metastasis after failure of third\u2011generation EGFR\u2011TKIs in EGFR\u2011mutant NSCLC: an ambispective cohort study"],"prefix":"10.1007","volume":"177","author":[{"given":"Xiaoyue","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hehui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shencun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"5544_CR1","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1016\/j.jtho.2016.06.029","volume":"11","author":"Y-S Li","year":"2016","unstructured":"Li Y-S, Jiang B-Y, Yang J-J et al (2016) Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations. J Thorac Oncol 11:1962\u20131969. https:\/\/doi.org\/10.1016\/j.jtho.2016.06.029","journal-title":"J Thorac Oncol"},{"key":"5544_CR2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jtho.2024.09.1385","volume":"20","author":"H Chen","year":"2025","unstructured":"Chen H, Yang S, Wang L et al (2025) High-Dose Furmonertinib in Patients With EGFR-Mutated NSCLC and Leptomeningeal Metastases: A Prospective Real-World Study. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 20:65\u201375. https:\/\/doi.org\/10.1016\/j.jtho.2024.09.1385","journal-title":"J Thorac Oncol Off Publ Int Assoc Study Lung Cancer"},{"key":"5544_CR3","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1002\/ijc.35460","volume":"157","author":"Y Xie","year":"2025","unstructured":"Xie Y, Fang H, Cheng W et al (2025) Furmonertinib in uncommon EGFR-mutated non-small cell lung cancer with central nervous system metastases: A retrospective cohort study. Int J Cancer 157:954\u2013963. https:\/\/doi.org\/10.1002\/ijc.35460","journal-title":"Int J Cancer"},{"key":"5544_CR4","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1200\/JCO.19.00457","volume":"38","author":"JCH Yang","year":"2020","unstructured":"Yang JCH, Kim S-W, Kim D-W et al (2020) Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol Off J Am Soc Clin Oncol 38:538\u2013547. https:\/\/doi.org\/10.1200\/JCO.19.00457","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"5544_CR5","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1093\/neuonc\/nox105","volume":"19","author":"JM Sep\u00falveda-S\u00e1nchez","year":"2017","unstructured":"Sep\u00falveda-S\u00e1nchez JM, Vaz M\u00c1, Bala\u00f1\u00e1 C et al (2017) Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Neuro-Oncol 19:1522\u20131531. https:\/\/doi.org\/10.1093\/neuonc\/nox105","journal-title":"Neuro-Oncol"},{"key":"5544_CR6","doi-asserted-by":"publisher","first-page":"oyaf079","DOI":"10.1093\/oncolo\/oyaf079","volume":"30","author":"P Xing","year":"2025","unstructured":"Xing P, Pu X, Zhou Y et al (2025) Efficacy and safety of dacomitinib in treatment-na\u00efve patients with advanced NSCLC and brain metastasis: A multicenter cohort study. Oncologist 30:oyaf079. https:\/\/doi.org\/10.1093\/oncolo\/oyaf079","journal-title":"Oncologist"},{"key":"5544_CR7","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.neo.2018.02.004","volume":"20","author":"R Endersby","year":"2018","unstructured":"Endersby R, Whitehouse J, Hii H et al (2018) A pre-clinical assessment of the pan-ERBB inhibitor dacomitinib in pediatric and adult brain tumors. Neoplasia N Y N 20:432\u2013442. https:\/\/doi.org\/10.1016\/j.neo.2018.02.004","journal-title":"Neoplasia N Y N"},{"key":"5544_CR8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13046-018-0690-x","volume":"37","author":"X Guo","year":"2018","unstructured":"Guo X, To KKW, Chen Z et al (2018) Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo. J Exp Clin Cancer Res CR 37:31. https:\/\/doi.org\/10.1186\/s13046-018-0690-x","journal-title":"J Exp Clin Cancer Res CR"},{"key":"5544_CR9","doi-asserted-by":"publisher","first-page":"iv84","DOI":"10.1093\/annonc\/mdx221","volume":"28","author":"E Le Rhun","year":"2017","unstructured":"Le Rhun E, Weller M, Brandsma D et al (2017) EANO-ESMO clinical practice guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol Off J Eur Soc Med Oncol 28:iv84\u2013iv99. https:\/\/doi.org\/10.1093\/annonc\/mdx221","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"5544_CR10","doi-asserted-by":"publisher","first-page":"102384","DOI":"10.1016\/j.esmoop.2024.102384","volume":"9","author":"C Fan","year":"2024","unstructured":"Fan C, Jiang Z, Teng C et al (2024) Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+ NSCLC: an expanded, single-arm, phase II clinical trial. ESMO Open 9:102384. https:\/\/doi.org\/10.1016\/j.esmoop.2024.102384","journal-title":"ESMO Open"},{"key":"5544_CR11","doi-asserted-by":"publisher","first-page":"e270","DOI":"10.1016\/S1470-2045(15)70057-4","volume":"16","author":"NU Lin","year":"2015","unstructured":"Lin NU, Lee EQ, Aoyama H et al (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270\u2013278. https:\/\/doi.org\/10.1016\/S1470-2045(15)70057-4","journal-title":"Lancet Oncol"},{"key":"5544_CR12","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1093\/neuonc\/now183","volume":"19","author":"M Chamberlain","year":"2017","unstructured":"Chamberlain M, Junck L, Brandsma D et al (2017) Leptomeningeal metastases: a RANO proposal for response criteria. Neuro-Oncol 19:484\u2013492. https:\/\/doi.org\/10.1093\/neuonc\/now183","journal-title":"Neuro-Oncol"},{"key":"5544_CR13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.lungcan.2020.12.008","volume":"152","author":"W Peng","year":"2021","unstructured":"Peng W, Pu X, Jiang M et al (2021) Dacomitinib induces objective responses in metastatic brain lesions of patients with EGFR-mutant non-small-cell lung cancer: A brief report. Lung Cancer Amst Neth 152:66\u201370. https:\/\/doi.org\/10.1016\/j.lungcan.2020.12.008","journal-title":"Lung Cancer Amst Neth"},{"key":"5544_CR14","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1111\/1759-7714.14222","volume":"12","author":"J Zhang","year":"2021","unstructured":"Zhang J, Wang Y, Liu Z et al (2021) Efficacy of dacomitinib in patients with EGFR-mutated NSCLC and brain metastases. Thorac Cancer 12:3407\u20133415. https:\/\/doi.org\/10.1111\/1759-7714.14222","journal-title":"Thorac Cancer"},{"key":"5544_CR15","doi-asserted-by":"publisher","first-page":"102068","DOI":"10.1016\/j.esmoop.2023.102068","volume":"8","author":"HA Jung","year":"2023","unstructured":"Jung HA, Park S, Lee S-H et al (2023) Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: A single-arm, phase II study. ESMO Open 8:102068. https:\/\/doi.org\/10.1016\/j.esmoop.2023.102068","journal-title":"ESMO Open"},{"key":"5544_CR16","doi-asserted-by":"publisher","first-page":"108710","DOI":"10.1016\/j.lungcan.2025.108710","volume":"207","author":"Y Yu","year":"2025","unstructured":"Yu Y, Pan Y, Zhou J et al (2025) Dacomitinib in the treatment of EGFR-mutated non-small cell lung cancer with brain metastases: An open-label, multicenter, phase II study. Lung Cancer Amst Neth 207:108710. https:\/\/doi.org\/10.1016\/j.lungcan.2025.108710","journal-title":"Lung Cancer Amst Neth"},{"key":"5544_CR17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/1759-7714.13712","volume":"12","author":"S Mizusaki","year":"2021","unstructured":"Mizusaki S, Otsubo K, Ninomiya T et al (2021) Remarkable response to dacomitinib in a patient with leptomeningeal carcinomatosis due to EGFR-mutant non-small cell lung cancer. Thorac Cancer 12:114\u2013116. https:\/\/doi.org\/10.1111\/1759-7714.13712","journal-title":"Thorac Cancer"},{"key":"5544_CR18","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1186\/s12885-025-14337-z","volume":"25","author":"S Wu","year":"2025","unstructured":"Wu S, Qiu Z, Shi H et al (2025) High-dose third-generation EGFR-TKIs combined with intrathecal pemetrexed in advanced EGFR-mutant NSCLC with leptomeningeal metastases following EGFR-TKI therapy. BMC Cancer 25:926. https:\/\/doi.org\/10.1186\/s12885-025-14337-z","journal-title":"BMC Cancer"},{"key":"5544_CR19","doi-asserted-by":"publisher","first-page":"1545174","DOI":"10.3389\/fonc.2025.1545174","volume":"15","author":"W Zhong","year":"2025","unstructured":"Zhong W, Wu L, Qiu Z et al (2025) Intrathecal pemetrexed chemotherapy combined with systemic therapy in patients with non-small cell lung cancer and leptomeningeal metastases: A retrospective study. Front Oncol 15:1545174. https:\/\/doi.org\/10.3389\/fonc.2025.1545174","journal-title":"Front Oncol"},{"key":"5544_CR20","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s11060-024-04716-0","volume":"169","author":"C Yu","year":"2024","unstructured":"Yu C, Xu T, Fang H et al (2024) High-dose furmonertinib combined with intraventricular chemotherapy as salvage therapy for leptomeningeal metastasis from EGFR exon 20 insertion-mutated lung cancer. J Neurooncol 169:203\u2013213. https:\/\/doi.org\/10.1007\/s11060-024-04716-0","journal-title":"J Neurooncol"},{"key":"5544_CR21","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.canlet.2018.01.021","volume":"421","author":"Y-F Fan","year":"2018","unstructured":"Fan Y-F, Zhang W, Zeng L et al (2018) Dacomitinib antagonizes multidrug resistance (MDR) in cancer cells by inhibiting the efflux activity of ABCB1 and ABCG2 transporters. Cancer Lett 421:186\u2013198. https:\/\/doi.org\/10.1016\/j.canlet.2018.01.021","journal-title":"Cancer Lett"},{"key":"5544_CR22","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1158\/1535-7163.MCT-07-2232","volume":"7","author":"AJ Gonzales","year":"2008","unstructured":"Gonzales AJ, Hook KE, Althaus IW et al (2008) Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor. Mol Cancer Ther 7:1880\u20131889. https:\/\/doi.org\/10.1158\/1535-7163.MCT-07-2232","journal-title":"Mol Cancer Ther"},{"key":"5544_CR23","doi-asserted-by":"publisher","first-page":"101834","DOI":"10.1016\/j.tranon.2023.101834","volume":"39","author":"Z Lu","year":"2024","unstructured":"Lu Z, Yi Y, Wang L et al (2024) Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors. Transl Oncol 39:101834. https:\/\/doi.org\/10.1016\/j.tranon.2023.101834","journal-title":"Transl Oncol"},{"key":"5544_CR24","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1001\/jamaoncol.2023.5013","volume":"10","author":"Y Okuma","year":"2024","unstructured":"Okuma Y, Kubota K, Shimokawa M et al (2024) First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial. JAMA Oncol 10:43\u201351. https:\/\/doi.org\/10.1001\/jamaoncol.2023.5013","journal-title":"JAMA Oncol"},{"key":"5544_CR25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.lungcan.2020.07.038","volume":"149","author":"V Singh","year":"2020","unstructured":"Singh V, Nambirajan A, Malik PS et al (2020) Spectrum of uncommon and compound epidermal growth factor receptor mutations in non-small-cell lung carcinomas with treatment response and outcome analysis: A study from India. Lung Cancer Amst Neth 149:53\u201360. https:\/\/doi.org\/10.1016\/j.lungcan.2020.07.038","journal-title":"Lung Cancer Amst Neth"},{"key":"5544_CR26","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41586-021-03898-1","volume":"597","author":"JP Robichaux","year":"2021","unstructured":"Robichaux JP, Le X, Vijayan RSK et al (2021) Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature 597:732\u2013737. https:\/\/doi.org\/10.1038\/s41586-021-03898-1","journal-title":"Nature"},{"key":"5544_CR27","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.21037\/tcr-23-95","volume":"12","author":"L-L Yang","year":"2023","unstructured":"Yang L-L, Luo X-Z, Xie L-L et al (2023) The treatment of patients with non-small cell lung cancer carrying uncommon EGFR mutations, HER2 mutations, or brain metastases: a systematic review of pre-clinical and clinical findings for dacomitinib. Transl Cancer Res 12:2197\u20132211. https:\/\/doi.org\/10.21037\/tcr-23-95","journal-title":"Transl Cancer Res"},{"key":"5544_CR28","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12885-022-09409-3","volume":"22","author":"B Zhang","year":"2022","unstructured":"Zhang B, Shi C, Gao Z et al (2022) Rationale and design of a phase II trial of dacomitinib in advanced non-small cell lung cancer patients with uncommon epidermal growth factor receptor mutations: A prospective and single arm study (DANCE study). BMC Cancer 22:294. https:\/\/doi.org\/10.1186\/s12885-022-09409-3","journal-title":"BMC Cancer"},{"key":"5544_CR29","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1186\/s12885-023-11465-2","volume":"23","author":"X Pu","year":"2023","unstructured":"Pu X, Zhou Y, Kong Y et al (2023) Efficacy and safety of dacomitinib in treatment-na\u00efve patients with advanced NSCLC harboring uncommon EGFR mutation: An ambispective cohort study. BMC Cancer 23:982. https:\/\/doi.org\/10.1186\/s12885-023-11465-2","journal-title":"BMC Cancer"},{"key":"5544_CR30","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/prot.26761","volume":"93","author":"IA Imam","year":"2025","unstructured":"Imam IA, Al Adawi S, Liu X et al (2025) L858R\/L718Q and L858R\/L792H mutations of EGFR inducing resistance against osimertinib by forming additional hydrogen bonds. Proteins 93:673\u2013683. https:\/\/doi.org\/10.1002\/prot.26761","journal-title":"Proteins"},{"key":"5544_CR31","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13045-018-0651-z","volume":"11","author":"Z Liu","year":"2018","unstructured":"Liu Z, Chen Z, Wang J et al (2018) Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered src family kinases involved in acquired resistance. J Hematol OncolJ Hematol Oncol 11:109. https:\/\/doi.org\/10.1186\/s13045-018-0651-z","journal-title":"J Hematol OncolJ Hematol Oncol"},{"key":"5544_CR32","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1097\/CM9.0000000000003136","volume":"137","author":"S Zhan","year":"2024","unstructured":"Zhan S, Cheng B, Liu X et al (2024) EGFR -mutant non-small cell lung cancer patients harboring CDK4 amplification show favorable response to afatinib: Two case reports. Chin Med J (Engl) 137:1465\u20131467. https:\/\/doi.org\/10.1097\/CM9.0000000000003136","journal-title":"Chin Med J (Engl)"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05544-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-026-05544-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-026-05544-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:01:41Z","timestamp":1778270501000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11060-026-05544-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["5544"],"URL":"https:\/\/doi.org\/10.1007\/s11060-026-05544-0","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"13 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Brain Hospital of Nanjing Medical University (Approval Number: 2025-KY154-01).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"76"}}