{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T12:07:43Z","timestamp":1769256463032,"version":"3.49.0"},"reference-count":99,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000646","name":"JSPS","doi-asserted-by":"publisher","award":["22\u00a0K09272"],"award-info":[{"award-number":["22\u00a0K09272"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>More than half of brain metastases (BMs) in patients with non-small cell lung cancer are diagnosed at the time of lung cancer diagnosis and are therefore potentially amenable to systemic treatment. Before the introduction of molecular targeting therapy, medical treatment was thought to be ineffective owing to the presence of the blood\u2013brain barrier (BBB). However, the molecular activities of cancer cells in the central nervous system affect the brain microenvironment, changing the function of the BBB and blood\u2013cerebrospinal fluid barrier, allowing drug delivery. In non-small cell lung cancer with driver gene mutations, BMs respond rapidly to molecular targeted drugs. Although the immune response is attenuated within BMs, it varies according to cancer type. In addition, the changes in immune response after immune checkpoint inhibitor administration vary from patient to patient. In treating BMs, which develop in the unique environment of the brain, it is particularly important to understand these pathologies and develop pathogenesis-based treatment strategies. Although drug therapy is effective against BMs, it is not curative, as BMs will eventually acquire resistance. In the era of molecular targeted agents, it is important to determine the most appropriate combination of treatments for each individual patient, taking into account the effectiveness of conventional local treatments and drug therapy, the presence of side effects, and the timing of their onset.<\/jats:p>","DOI":"10.1093\/jjco\/hyaf155","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:56:21Z","timestamp":1758282981000},"page":"12-23","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenesis-based treatment strategies for brain metastases from non-small cell cancer"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-0049","authenticated-orcid":false,"given":"Toshihiko","family":"Iuchi","sequence":"first","affiliation":[{"name":"Division of Neurological Surgery, Chiba Cancer Center , 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Shingyoji","sequence":"additional","affiliation":[{"name":"Division of Respirology, Chiba Cancer Center , 666-2 intone-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Ashinuma","sequence":"additional","affiliation":[{"name":"Division of Respirology, Chiba Cancer Center , 666-2 intone-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Respirology, Chiba Cancer Center , 666-2 intone-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzo","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Neurological Surgery, Chiba Cancer Center , 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiki","family":"Setoguchi","sequence":"additional","affiliation":[{"name":"Division of Neurological Surgery, Chiba Cancer Center , 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Hosono","sequence":"additional","affiliation":[{"name":"Division of Neurological Surgery, Chiba Cancer Center , 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukasa","family":"Sakaida","sequence":"additional","affiliation":[{"name":"Division of Neurological Surgery, Chiba Cancer Center , 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"2026012223580477800_ref1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s10545-013-9608-0","article-title":"Blood\u2013brain barrier structure and function and the challenges for CNS drug delivery","volume":"36","author":"Abbott","year":"2013","journal-title":"J Inherit Metab Dis"},{"key":"2026012223580477800_ref2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/nm.2072","article-title":"Real-time imaging reveals the single steps of brain metastasis formation","volume":"16","author":"Kienast","year":"2010","journal-title":"Nat Med"},{"key":"2026012223580477800_ref3","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s40478-019-0788-1","article-title":"Response of the neurovascular unit to brain metastatic breast cancer cells","volume":"7","author":"Hask\u00f3","year":"2019","journal-title":"Acta Neuropathol Commun"},{"key":"2026012223580477800_ref4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s43018-021-00321-6","article-title":"Keeping brain metastases dormant. Nat","volume":"3","author":"Khan","year":"2022","journal-title":"Cancer."},{"key":"2026012223580477800_ref5","doi-asserted-by":"publisher","first-page":"5277","DOI":"10.1074\/jbc.M210063200","article-title":"Vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability","volume":"278","author":"Lee","year":"2003","journal-title":"J Biol Chem"},{"key":"2026012223580477800_ref6","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1111\/cts.12978","article-title":"Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer","volume":"14","author":"Bao","year":"2021","journal-title":"Clin Tranl Sci"},{"key":"2026012223580477800_ref7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12987-020-00196-2","article-title":"Choroid plexus and the blood\u2013cerebrospinal fluid barrier in disease","volume":"17","author":"Sol\u00e1r","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"2026012223580477800_ref8","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1093\/jnen\/nlv030","article-title":"The choroid plexus in healthy and diseased brain","volume":"75","author":"Kaur","year":"2016","journal-title":"J Neuropathol Exp Neurol"},{"key":"2026012223580477800_ref9","doi-asserted-by":"publisher","first-page":"506","DOI":"10.3171\/jns.1970.33.5.0506","article-title":"PC, human choroid plexus: a light and electron microscopic study","volume":"33","author":"DohrmannGJ","year":"1970","journal-title":"J Neurosurg"},{"key":"2026012223580477800_ref10","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1126\/science.aaz5626","article-title":"Human CNS barrier-forming organoids with cerebrospinal fluid production","volume":"369","author":"Pellegrini","year":"2020","journal-title":"Science."},{"key":"2026012223580477800_ref11","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.2174\/1381612822666160726112115","article-title":"Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier","volume":"22","author":"Strazielle","year":"2016","journal-title":"Curr Pharm Des"},{"key":"2026012223580477800_ref12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1158\/1078-0432.CCR-19-1871","article-title":"Prelinical comparison of the blood-brain barrier permeability of osimertinib with other EGFR TKIs","volume":"27","author":"Colclough","year":"2021","journal-title":"Clin Cancer Res"},{"key":"2026012223580477800_ref13","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.expneurol.2015.07.027","article-title":"A balanced view of the cerebrospinal liquid composition and functions: focus on adult humans","volume":"273","author":"Spector","year":"2015","journal-title":"Exp Neurol"},{"key":"2026012223580477800_ref14","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.cell.2017.02.025","article-title":"Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis","volume":"168","author":"Boire","year":"2017","journal-title":"Cell."},{"key":"2026012223580477800_ref15","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2","volume":"4","author":"Ilife","year":"2012","journal-title":"Sci Tranl Med"},{"key":"2026012223580477800_ref16","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature."},{"key":"2026012223580477800_ref17","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol"},{"key":"2026012223580477800_ref18","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.tins.2021.07.002","article-title":"Macrophages on the margin: choroid plexus immune responses","volume":"44","author":"Cui","year":"2021","journal-title":"Trends Neurosci"},{"key":"2026012223580477800_ref19","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1016\/j.cell.2020.05.007","article-title":"Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells","volume":"181","author":"Klemm","year":"2020","journal-title":"Cell."},{"key":"2026012223580477800_ref20","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1093\/annonc\/mdz207","article-title":"Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer","volume":"30","author":"Kudo","year":"2019","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref21","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/cas.12941","article-title":"Gene aberrations for precision medicine against lung adenocarcinoma","volume":"107","author":"Saito","year":"2016","journal-title":"Cancer Sci"},{"key":"2026012223580477800_ref22","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1007\/s10147-014-0760-9","article-title":"Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations","volume":"20","author":"Iuchi","year":"2015","journal-title":"Int J Clin Oncol"},{"key":"2026012223580477800_ref23","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1093\/neuonc\/nov266","article-title":"Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor","volume":"18","author":"Takano","year":"2016","journal-title":"Neuro Oncol"},{"key":"2026012223580477800_ref24","first-page":"457","article-title":"Stereotactic radiosurgery with and without whole-brain radiation therapy for brain metastases. Secondary analyses of the JROSG 99-1 randomized clinical trial. JAMA","volume":"1","author":"Aoyama","year":"2015","journal-title":"Oncol."},{"key":"2026012223580477800_ref25","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1001\/jama.2016.9839","article-title":"Whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases","volume":"316","author":"Brown","year":"2016","journal-title":"A randomized clinical trial JAMA"},{"key":"2026012223580477800_ref26","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.scr.2016.02.031","article-title":"Implications of irradiating the subventricular zone stem cell niche","volume":"16","author":"Capilla-Gonzalez","year":"2016","journal-title":"Stem Cell Res"},{"key":"2026012223580477800_ref27","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/S1470-2045(17)30441-2","article-title":"Postoperative stereotactic radiosurgery compared with whole-brain radiotherapy for resected metastatic brain disease (NCCTG N107C\/CEC\u00b73): a multicentre, randomised, controlled, phase 3 trial","volume":"18","author":"Brown","year":"2017","journal-title":"Lancet Oncol"},{"key":"2026012223580477800_ref28","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ijrobp.2024.09.029","article-title":"An exploratory analysis of the conditional neurocognitive function failure risk in patients receiving whole-brain radiation therapy for brain metastases on NRG oncology CC001","volume":"121","author":"Cherng","year":"2025","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026012223580477800_ref29","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1200\/JCO.19.02767","article-title":"Hippocampal avoidance during whole-brain radiation therapy plus memantine for patients with brain metastases: phase III trial NRG oncology CC001","volume":"38","author":"Brown","year":"2020","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref30","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1093\/neuonc\/not114","article-title":"Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial","volume":"15","author":"Brown","year":"2013","journal-title":"Neuro-Oncol."},{"key":"2026012223580477800_ref31","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S1470-2045(14)70061-0","article-title":"Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study","volume":"15","author":"Yamamoto","year":"2014","journal-title":"Lancet Oncol"},{"key":"2026012223580477800_ref32","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1200\/JCO.2025.43.16_suppl.2011","article-title":"Stereotactic radiation versus hippocampal avoidance whole brain radiation in patients with 5\u201320 brain metastases: a multicenter, phase 3 randomized trial","volume":"43","author":"Aizer","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref33","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.3390\/cancers15092432","article-title":"Novel mechanism and future opportunities for the management of radiation necrosis in patients treated for brain metastases in the era of immunotherapy","volume":"15","author":"Varios","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2026012223580477800_ref34","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0360-3016(99)00507-6","article-title":"Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05","volume":"47","author":"Shaw","year":"2000","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026012223580477800_ref35","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13014-020-01522-6","article-title":"A multi-center analysis of single-fraction versus hypofractionated stereotactic radiosurgery for the treatment of brain metastasis","volume":"15","author":"Remick","year":"2020","journal-title":"Radiat Oncol"},{"key":"2026012223580477800_ref36","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13014-019-1228-x","article-title":"Radiological diagnosis of brain radiation necrosis after cranial irradiation for brain tumor: a systematic review","volume":"14","author":"Furuse","year":"2019","journal-title":"Radiat Oncol"},{"key":"2026012223580477800_ref37","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11060-010-0222-9","article-title":"Morphologic magnetic resonance imaging features of therapy-induced cerebral necrosis","volume":"101","author":"Rogers","year":"2011","journal-title":"J Neurooncol"},{"key":"2026012223580477800_ref38","first-page":"272","article-title":"A prospective multicenter single-arm clinical trial of bevacizumab for patients with surgically untreatable symptomatic brain radiation necrosis","volume":"3","author":"Furuse","year":"2016","journal-title":"Neurooncol Pract"},{"key":"2026012223580477800_ref39","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1200\/JCO.2018.79.0006","article-title":"Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non\u2013small-cell lung cancer","volume":"36","author":"Arbour","year":"2018","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref40","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s11060-021-03790-y","article-title":"The effect of surgery on radiation necrosis in irradiated brain metastases: extent of resection and long-term clinical and radiographic outcomes","volume":"153","author":"Newman","year":"2021","journal-title":"J Neurooncol"},{"key":"2026012223580477800_ref41","doi-asserted-by":"publisher","first-page":"555","DOI":"10.3171\/2021.9.JNS211797","article-title":"Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis","volume":"137","author":"Yomo","year":"2021","journal-title":"J Neurosurg"},{"key":"2026012223580477800_ref42","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.ijrobp.2017.04.006","article-title":"Single-fraction stereotactic radiosurgery (SRS) alone versus surgical resection and SRS for large brain metastases: a multi-institutional analysis","volume":"99","author":"Prabhu","year":"2017","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026012223580477800_ref43","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.ijrobp.2008.05.035","article-title":"A matched-pair analysis comparing whole-brain radiotherapy plus stereotactic radiosurgery versus surgery plus whole-brain radiotherapy and a boost to the metastatic site for one or two brain metastases","volume":"73","author":"Rades","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026012223580477800_ref44","doi-asserted-by":"publisher","first-page":"246","DOI":"10.14791\/btrt.2023.0032","article-title":"Treatment outcome of the brain metastases in Peri-Rolandic area: comparison between surgery and stereotactic radiosurgery","volume":"11","author":"Jung","year":"2023","journal-title":"Brain Tumor Res Treat"},{"key":"2026012223580477800_ref45","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s13014-017-0917-6","article-title":"Early motor function after local treatment of brain metastases in the motor cortex region with stereotactic radiotherapy\/radiosurgery or microsurgical resection: a retrospective study of two consecutive cohorts","volume":"12","author":"Pintea","year":"2017","journal-title":"Radiat Oncol"},{"key":"2026012223580477800_ref46","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s11060-018-03008-8","article-title":"Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases","volume":"140","author":"Dohm","year":"2018","journal-title":"J Neurooncol"},{"key":"2026012223580477800_ref47","doi-asserted-by":"publisher","DOI":"10.1093\/nop\/npae118","article-title":"Risk factors for type I leptomeningeal metastasis derived from non-small cell lung cancer and the impact of treatment for brain metastases on its development","volume":"12","author":"Iuchi","year":"2024","journal-title":"Neurooncol Pract"},{"key":"2026012223580477800_ref48","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1093\/annonc\/mds529","article-title":"Erlotinib as second-line treatment in patients with advanced non-small cell lung cancer and asymptomatic brain metastases","volume":"24","author":"Wu","year":"2013","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref49","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.lungcan.2013.08.016","article-title":"Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma","volume":"82","author":"Iuchi","year":"2013","journal-title":"Lung Cancer"},{"key":"2026012223580477800_ref50","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.1200\/JCO.2018.78.3118","article-title":"CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small cell lung cancer","volume":"36","author":"Reungwetwattana","year":"2018","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref51","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1200\/JCO.2018.77.9363","article-title":"CNS efficacy of osimertinib in patients with T790M-positive advanced non\u2013small-cell lung cancer: data from a randomized phase III trial (AURA3)","volume":"36","author":"Wu","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref52","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1913662","article-title":"Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC","volume":"382","author":"Ramalingam","year":"2020","journal-title":"N Engl J Med"},{"key":"2026012223580477800_ref53","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1200\/JCO.23.02219","article-title":"CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor\u2013mutated advanced non\u2013small-cell lung cancer","volume":"42","author":"J\u00e4nne","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref54","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/s41467-023-35961-y","article-title":"Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer","volume":"14","author":"Chmielecki","year":"2023","journal-title":"Nat Commun"},{"key":"2026012223580477800_ref55","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.annonc.2024.05.541","article-title":"Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA","volume":"35","author":"Felip","year":"2024","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref56","doi-asserted-by":"publisher","first-page":"S1245","DOI":"10.1016\/j.annonc.2024.08.2297","article-title":"Mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: an early analysis from the phase III MARIPOSA study","volume":"35","author":"Besse","year":"2024","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref57","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1200\/JCO.2015.63.5888","article-title":"Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non\u2013small-cell lung cancer: results from PROFILE 1014","volume":"34","author":"Solomon","year":"2016","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref58","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1704795","article-title":"Alectinib versus crizotinib in untreated ALK-positive non\u2013xmall-cell lung cancer","volume":"377","author":"Peters","year":"2017","journal-title":"N Engl J Med"},{"key":"2026012223580477800_ref59","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1056\/NEJMoa1810171","article-title":"Brigatinib versus crizotinib in ALK-positive non\u2013small-cell lung cancer","volume":"379","author":"Camidge","year":"2018","journal-title":"N Engl J Med"},{"key":"2026012223580477800_ref60","doi-asserted-by":"publisher","first-page":"3592","DOI":"10.1200\/JCO.20.00505","article-title":"Brigatinib versus crizotinib in advanced ALK inhibitor-na\u00efve ALK positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial","volume":"38","author":"Camidge","year":"2020","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref61","doi-asserted-by":"publisher","first-page":"4720","DOI":"10.1021\/jm500261q","article-title":"Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetra-hydro-2H-8,4-(metheno) pyrazolo [4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations","volume":"57","author":"Johnson","year":"2014","journal-title":"J Med Chem"},{"key":"2026012223580477800_ref62","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1200\/JCO.21.02278","article-title":"Post hoc analysis of lorlatinib intracranial efficacy and safety in patients with ALK-positive advanced non-small cell lung cancer from the phase III CROWN study","volume":"40","author":"Solomon","year":"2022","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref63","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S2213-2600(22)00437-4","article-title":"Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study","volume":"11","author":"Solomon","year":"2023","journal-title":"Lancet Respir Med"},{"key":"2026012223580477800_ref64","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1016\/j.jtho.2021.07.035","article-title":"Brigatinib versus crizotinib in ALK inhibitor naive advanced ALK-positive NSCLC: final results of phase3 ALTA-1L trial","volume":"16","author":"Camidge","year":"2021","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref65","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.annonc.2020.04.478","article-title":"Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study","volume":"31","author":"Mok","year":"2020","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref66","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1200\/JCO.24.00581","article-title":"Lorlatinib versus crizotinib in patients with advanced ALK-positive non\u2013small cell lung cancer: 5-year outcomes from the phase III CROWN study","volume":"42","author":"Solomon","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref67","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for lung cancers with KRAS p.G12C mutation","volume":"384","author":"Skoulidis","year":"2021","journal-title":"N Engl J Med"},{"key":"2026012223580477800_ref68","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/S0140-6736(23)00221-0","article-title":"Sotorasib versus docetaxel for previously treated non-small- cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial","volume":"401","author":"Langen","year":"2023","journal-title":"Lancet"},{"key":"2026012223580477800_ref69","doi-asserted-by":"publisher","first-page":"e2200621","DOI":"10.1200\/PO.22.00621","article-title":"Incidence of brain metastases and preliminary evidence of intracranial activity with sotorasib in patients with KRASG12C-mutant non-small-cell lung cancer","volume":"7","author":"Lamberti","year":"2023","journal-title":"JCO Precis Oncol"},{"key":"2026012223580477800_ref70","doi-asserted-by":"crossref","first-page":"107425","DOI":"10.1016\/j.lungcan.2023.107425","article-title":"Brief report on the efficacy of sotorasib in KRAS-mutated NSCLC patients with brain metastases","volume":"87","author":"Lebouille-Veldman","year":"2024","journal-title":"Lung Cancer"},{"key":"2026012223580477800_ref71","doi-asserted-by":"publisher","first-page":"4852","DOI":"10.1200\/JCO.23.01361","article-title":"Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial","volume":"41","author":"Goto","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref72","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s10143-025-03418-z","article-title":"The safety and efficacy of anti-PD-1\/PD-L1 monoclonal antibodies for lung cancer brain metastasis: a systematic review and meta-analysis on brain metastasis","volume":"48","author":"Delbari","year":"2025","journal-title":"Neurosurg Rev"},{"key":"2026012223580477800_ref73","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1200\/JCO.19.03136","article-title":"Updated analysis from KEYNOTE-189: Pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non\u2013small-cell lung cancer","volume":"38","author":"Gadgeel","year":"2020","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref74","doi-asserted-by":"publisher","first-page":"S845","DOI":"10.1016\/j.annonc.2024.08.1387","article-title":"Effects of immune checkpoint inhibitors for EGFR-wild\/ALK-negative NSCLC patients with untreated brain metastases","volume":"35","author":"Iuchi","year":"2024","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref75","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijrobp.2022.03.020","article-title":"Graded prognostic assessment (GPA) for patients with lung cancer and brain metastases: initial report of the small cell lung cancer GPA and update of the non-small cell lung cancer GPA including the effect of programmed death ligand 1 and other prognostic factors","volume":"114","author":"Sperduto","year":"2022","journal-title":"Int J Radiation Oncol Biol Phys"},{"key":"2026012223580477800_ref76","doi-asserted-by":"publisher","first-page":"S278","DOI":"10.1016\/j.ijrobp.2010.07.663","article-title":"Brain deformation after planning for IMRT may affect the outcome of patients with glioblastoma","volume":"78","author":"Iuchi","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026012223580477800_ref77","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1227\/NEU.0000000000001096","article-title":"Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis","volume":"79","author":"Patel","year":"2016","journal-title":"Neurosurgery."},{"key":"2026012223580477800_ref78","volume-title":"WHO classification of tumours","author":"Central Nervous System Tumours","year":"2021","edition":"5th"},{"key":"2026012223580477800_ref79","doi-asserted-by":"publisher","first-page":"iv84","DOI":"10.1093\/annonc\/mdx221","article-title":"EANO\u2013ESMO clinical practice guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours","volume":"28","author":"Le Rhun","year":"2017","journal-title":"Ann Oncol"},{"key":"2026012223580477800_ref80","first-page":"448","article-title":"Risk factors for type I leptomeningeal metastasis derived from non-small cell lung cancer and the impact of treatment for brain metastases on its development","volume":"12","author":"Iuchi","year":"2024","journal-title":"Neurooncology Pract"},{"key":"2026012223580477800_ref81","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1016\/j.jtho.2016.06.029","article-title":"Leptomeningeal metastases in patients with NSCLC with EGFR mutations","volume":"11","author":"Li","year":"2016","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref82","first-page":"4177","article-title":"Cerebrospinal fluid penetration rate and efficacy of afatinib in patients with EGFR mutation-positive non-small cell lung cancer with leptomeningeal carcinomatosis: a multicenter prospective study","volume":"37","author":"Tamiya","year":"2017","journal-title":"Anticancer Res"},{"key":"2026012223580477800_ref83","doi-asserted-by":"crossref","first-page":"4527","DOI":"10.18632\/oncotarget.2886","article-title":"A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer","volume":"6","author":"Jackman","year":"2015","journal-title":"Oncotarget."},{"key":"2026012223580477800_ref84","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1097\/JTO.0b013e318294c8e8","article-title":"Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer","volume":"8","author":"Lee","year":"2013","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref85","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.jtho.2019.12.113","article-title":"Osimertinib for patients with leptomeningeal metastases associated with EGFR T790M-positive advanced NSCLC: the AURA leptomeningeal metastases analysis","volume":"15","author":"Ahn","year":"2020","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref86","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1200\/JCO.19.00457","article-title":"Osimertinib in patients with epidermal growth factor receptor mutation-positive non\u2013small-cell lung cancer and leptomeningeal metastases: the BLOOM study","volume":"38","author":"Yang","year":"2019","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref87","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/1759-7714.13738","article-title":"Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR-mutation non-small cell lung cancer: a phase II single-arm prospective clinical trial","volume":"12","author":"Lu","year":"2012","journal-title":"Thoracic Cancer"},{"key":"2026012223580477800_ref88","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s11060-013-1199-y","article-title":"Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung","volume":"115","author":"Lee","year":"2013","journal-title":"J Neurooncol"},{"key":"2026012223580477800_ref89","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1002\/jcph.2056","article-title":"Evaluation of lorlatinib cerebrospinal fluid concentrations in relation to target concentrations for anaplastic lymphoma kinase (ALK) inhibition","volume":"62","author":"Sun","year":"2022","journal-title":"J Clin Pharmacol"},{"key":"2026012223580477800_ref90","doi-asserted-by":"publisher","first-page":"S382","DOI":"10.1016\/j.jtho.2018.08.379","article-title":"Brain penetration of lorlatinib and cumulative incidence rates for CNS and non C-NS progression from a phase 1\/2 study","volume":"13","author":"Bauer","year":"2018","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref91","doi-asserted-by":"publisher","first-page":"e443","DOI":"10.1200\/JCO.2010.34.1313","article-title":"CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib","volume":"29","author":"Costa","year":"2011","journal-title":"J Clin Oncol"},{"key":"2026012223580477800_ref92","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/s11060-016-2184-z","article-title":"Alectinib\u2019s activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case series","volume":"129","author":"Metro","year":"2016","journal-title":"J Neurooncol"},{"key":"2026012223580477800_ref93","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s11523-020-00702-4","article-title":"Brain penetration of lorlatinib: cumulative incidences of CNS and non-CNS progression with lorlatinib in patients with previously treated ALK-positive non-small-cell lung cancer","volume":"15","author":"Bauer","year":"2020","journal-title":"Target Oncol"},{"key":"2026012223580477800_ref94","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1016\/j.jtho.2020.04.019","article-title":"An international real-world analysis of the efficacy and safety of lorlatinib through early or expanded access programs in patients with tyrosine kinase inhibi- tor\u2013refractory ALK-positive or ROS1-positive NSCLC","volume":"15","author":"Zhu","year":"2020","journal-title":"J Thorac Oncol"},{"key":"2026012223580477800_ref95","doi-asserted-by":"publisher","first-page":"1758835920980558","DOI":"10.1177\/1758835920980558","article-title":"Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program","volume":"13","author":"Frost","year":"2021","journal-title":"Ther Adv Med Oncol"},{"key":"2026012223580477800_ref96","doi-asserted-by":"publisher","first-page":"5955","DOI":"10.1038\/s41467-021-25860-5","article-title":"Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases","volume":"12","author":"Prakadan","year":"2021","journal-title":"Nat Commun"},{"key":"2026012223580477800_ref97","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41591-020-0918-0","article-title":"Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis","volume":"26","author":"Brastianos","year":"2020","journal-title":"Nat Med"},{"key":"2026012223580477800_ref98","doi-asserted-by":"publisher","first-page":"5954","DOI":"10.1038\/s41467-021-25859-y","article-title":"Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis","volume":"12","author":"Brastianos","year":"2021","journal-title":"Nat Commun"},{"key":"2026012223580477800_ref99","doi-asserted-by":"publisher","first-page":"4109","DOI":"10.1158\/1078-0432.CCR-21-1694","article-title":"Single-cell characterization of the immune microenvironment of melanoma brain and leptomeningeal metastases","volume":"27","author":"Smalley","year":"2021","journal-title":"Clin Cancer Res"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/1\/12\/64539330\/hyaf155.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/56\/1\/12\/64539330\/hyaf155.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T04:58:10Z","timestamp":1769144290000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/56\/1\/12\/8276973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,10,7]]},"published-print":{"date-parts":[[2026,1,9]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyaf155","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,10,7]]}}}