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LM remains largely refractory to treatment and lacks standardized treatment consensus, with a low intracranial objective response rate (iORR) of 20% and a short median intracranial progression\u2010free survival (iPFS) of 2.2 months. In this study, adult patients with breast cancer\u2010related LM received intraventricular thiotepa combined with methotrexate. The primary endpoint was achieved with an iORR of 45.8% (11 out of 24, 95% CI: 25.55\u201367.18%), and the intracranial disease control rate was 58.3% (14 out of 24, 95% CI: 36.64\u201377.89%). From treatment initiation, the median iPFS and overall survival were 7.9 months (95% CI: 5.3\u2013not estimable) and 11.7 months (95% CI: 5.7\u2013not estimable), respectively. Grade 3\u20134 treatment\u2010related adverse events occurred in 62.5% (15 out of 24) of patients, most commonly thrombocytopenia (37.5%) and leukopenia (33.3%), with no Grade 5 toxicities. The exploratory study indicated that two proteins in CSF and four plasma proteins were significantly associated with iORR. Overall, the regimen was feasible and demonstrated a manageable safety profile, with a preliminary signal of clinical benefit warranting further investigation.<\/jats:p>","DOI":"10.1002\/mco2.71014","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:31:38Z","timestamp":1789021898000},"source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Intraventricular Thiotepa in Combination With Methotrexate for Leptomeningeal Metastasis From Breast Cancer (NJMU\u2010BC04): A Single\u2010Arm Phase II Study"],"prefix":"10.1002","volume":"7","author":[{"given":"Wenbin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Breast Surgery Department of General Surgery The First Affiliated Hospital with Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hehui","family":"Fang","sequence":"additional","affiliation":[{"name":"Brain Metastases Diagnosis and Treatment Centre The Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Oncology Jiangsu Cancer Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology Shanghai Medical College Fudan University  Shanghai China"},{"name":"Phase I Unit Fudan University Shanghai Cancer Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shencun","family":"Fang","sequence":"additional","affiliation":[{"name":"Brain Metastases Diagnosis and Treatment Centre The Affiliated Brain Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Department of General Surgery The First Affiliated Hospital with Nanjing Medical University  Nanjing China"},{"name":"Jiangsu Key Lab of Cancer Biomarkers Prevention and Treatment Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital with Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.01.020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-2042-y"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19910315)67:6<1685::AID-CNCR2820670635>3.0.CO;2-M"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5911"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cad.0000236313.50833.ee"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdi371"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-019-05317-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx221"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa298"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.35.9.1274"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005956925637"},{"issue":"4","key":"e_1_2_11_13_1","first-page":"703","article-title":"Clinical Pharmacology of Intrathecal Methotrexate. 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