{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:40:30Z","timestamp":1788903630218,"version":"build-2803163510"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Gastric cancer is the fifth most common cancer worldwide and leptomeningeal carcinomatosis (LM) occurs in 0.06% of gastric cancers. As such, trials are difficult to power and quantitative analyses difficult to standardize. We composed a review and analysis of 47 recent cases to be used as a comprehensive resource for an oncologist faced with managing this highly morbid, rapidly fatal disease. Gold-standard of diagnosis of LM is through cerebral spinal fluid (CSF) cytology; MRI is the preferred imaging modality to identify LM. However, repeated lumbar punctures and imaging studies are often required to establish diagnosis. Negative results do not rule out LM. Treatment includes radiation and intrathecal chemotherapy, most commonly with methotrexate. Systemic treatment with chemotherapy and immunotherapy is also used. Median survival was 2\u00a0months. Intrathecal methotrexate was most commonly dosed at 10-12\u00a0mg and treatment continued till symptom resolution, serial lumbar punctures with negative cytology, decrease and stabilization of CSF carcinoembryonic antigen (CEA) levels, progression of disease, or poor functional status. The maximum survival was 12\u00a0months. The results of this review indicate that suspicion for leptomeningeal disease should be high in any patient with gastric malignancy or with symptoms consistent with malignancy. Treatment on a biweekly to bi-monthly basis and the addition of systemic therapy to intrathecal therapy should be studied in a matched prospective manner. And in the absence of this information, treatment with at least intrathecal chemotherapy and radiation therapy should be considered in those with a performance status conducive to continued treatment.<\/jats:p>","DOI":"10.1007\/s10120-025-01597-8","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T04:23:38Z","timestamp":1741926218000},"page":"311-325","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Leptomeningeal carcinomatosis in gastric cancer: A Review"],"prefix":"10.1007","volume":"28","author":[{"given":"Simran","family":"Arjani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyein","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawneet","family":"Chadha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda","family":"Yousuf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-8748","authenticated-orcid":false,"given":"Enrico","family":"Castellucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"1597_CR1","unstructured":"Worldwide cancer data: Global cancer statistics for the most common cancers in the world. WCRF International. Updated Mar 23, 2022."},{"key":"1597_CR2","unstructured":"Key Statistics About Stomach Cancer. American Cancer Society. Updated Jan 19, 2024."},{"key":"1597_CR3","unstructured":"Stomach: Stage Distribution of SEER Incidence Cases, 2012\u20132021. National Cancer Institute. Updated Apr 17, 2024."},{"key":"1597_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30060442","author":"A Nguyen","year":"2023","unstructured":"Nguyen A, Nguyen A, Dada OT, et al. Leptomeningeal metastasis: a review of the pathophysiology, diagnostic methodology, and therapeutic landscape. Current Oncol. 2023. https:\/\/doi.org\/10.3390\/curroncol30060442.","journal-title":"Current Oncol"},{"key":"1597_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030685","author":"L Marenco-Hillembrand","year":"2023","unstructured":"Marenco-Hillembrand L, Bamimore MA, Rosado-Philippi J, et al. The evolving landscape of leptomeningeal cancer from solid tumors: a systematic review of clinical trials. Cancers. 2023. https:\/\/doi.org\/10.3390\/cancers15030685.","journal-title":"Cancers"},{"key":"1597_CR6","doi-asserted-by":"publisher","DOI":"10.1023\/a:1006156204385","author":"M Kim","year":"1999","unstructured":"Kim M. Intracranial involvement by metastatic advanced gastric carcinoma - PubMed. J neuro-oncol. 1999. https:\/\/doi.org\/10.1023\/a:1006156204385.","journal-title":"J neuro-oncol."},{"issue":"6","key":"1597_CR7","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1227\/NEU.0000000000000132","volume":"73","author":"S Knafo","year":"2013","unstructured":"Knafo S, Pallud J, Le Rhun E, et al. Intradural extramedullary spinal metastases of non-neurogenic origin: a distinct clinical entity or a subtype of leptomeningeal metastasis? A case-control study Neurosurgery. 2013;73(6):923\u201332. https:\/\/doi.org\/10.1227\/NEU.0000000000000132.","journal-title":"A case-control study Neurosurgery"},{"issue":"6","key":"1597_CR8","first-page":"1103","volume":"68","author":"DA Seehusen","year":"2003","unstructured":"Seehusen DA, Reeves MM, Fomin DA. Cerebrospinal fluid analysis. Am Family Phys. 2003;68(6):1103\u20138.","journal-title":"Am Family Phys"},{"key":"1597_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042745","author":"WG Leen","year":"2012","unstructured":"Leen WG, Willemsen MA, Wevers RA, Verbeek MM. Cerebrospinal Fluid Glucose and Lactate: Age-Specific Reference Values and Implications for Clinical Practice. PLoS ONE. 2012. https:\/\/doi.org\/10.1371\/journal.pone.0042745.","journal-title":"PLoS ONE"},{"key":"1597_CR10","unstructured":"Indicator Metadata Registry List: Mean fasting blood glucose. World Health Organization. https:\/\/www.who.int\/data\/gho\/indicator-metadata-registry\/imr-details\/2380"},{"issue":"11","key":"1597_CR11","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/s0009-9260(99)91181-9","volume":"54","author":"DA Collie","year":"1999","unstructured":"Collie DA, Brush JP, Lammie GA, et al. Imaging features of leptomeningeal metastases. Clin Radiol. 1999;54(11):765\u201371. https:\/\/doi.org\/10.1016\/s0009-9260(99)91181-9.","journal-title":"Clin Radiol"},{"issue":"2","key":"1597_CR12","doi-asserted-by":"publisher","first-page":"619","DOI":"10.21873\/anticanres.15519","volume":"42","author":"P Palmisciano","year":"2022","unstructured":"Palmisciano P, Sagoo NS, Kharbat AF, et al. Leptomeningeal Metastases of the Spine: A Systematic Review. Anticancer Res. 2022;42(2):619\u201328. https:\/\/doi.org\/10.21873\/anticanres.15519.","journal-title":"Anticancer Res"},{"issue":"4","key":"1597_CR13","first-page":"639","volume":"15","author":"DJ Schumacher","year":"1994","unstructured":"Schumacher DJ, Tien RD, Friedman H. Gadolinium enhancement of the leptomeninges caused by hydrocephalus: a potential mimic of leptomeningeal metastasis. AJNR Am J Neuroradiol. 1994;15(4):639\u201341.","journal-title":"AJNR Am J Neuroradiol"},{"issue":"2","key":"1597_CR14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1053\/ctrv.1999.0119","volume":"25","author":"SA Grossman","year":"1999","unstructured":"Grossman SA, Krabak MJ. Leptomeningeal carcinomatosis. Cancer Treat Rev. 1999;25(2):103\u201319. https:\/\/doi.org\/10.1053\/ctrv.1999.0119.","journal-title":"Cancer Treat Rev"},{"key":"1597_CR15","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20272","author":"G Nayar","year":"2017","unstructured":"Nayar G, Ejikeme T, Chongsathidkiet P, et al. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget. 2017. https:\/\/doi.org\/10.18632\/oncotarget.20272.","journal-title":"Oncotarget"},{"key":"1597_CR16","unstructured":"Batool A, Kasi A. Leptomeningeal Carcinomatosis. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK499862\/"},{"key":"1597_CR17","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i8.2120","author":"J-W Guo","year":"2014","unstructured":"Guo J-W, Zhang X-T, Chen X-S, et al. Leptomeningeal carcinomatosis as the initial manifestation of gastric adenocarcinoma: A case report. WJG. 2014. https:\/\/doi.org\/10.3748\/wjg.v20.i8.2120.","journal-title":"WJG"},{"key":"1597_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4116-0","author":"X-D Jiao","year":"2018","unstructured":"Jiao X-D, Ding C, Zang Y-S, Yu G. Rapid symptomatic relief of HER2-positive gastric cancer leptomeningeal carcinomatosis with lapatinib, trastuzumab and capecitabine: a case report. BMC Cancer. 2018. https:\/\/doi.org\/10.1186\/s12885-018-4116-0.","journal-title":"BMC Cancer"},{"key":"1597_CR19","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_108_19","author":"JH Cho","year":"2021","unstructured":"Cho JH, Sim M-H, Kim SY, et al. Analysis of intrapatient heterogeneity of circulating tumor cells at the single-cell level in the cerebrospinal fluid of a patient with metastatic gastric cancer. J Cancer Res Therapeutics. 2021. https:\/\/doi.org\/10.4103\/jcrt.JCRT_108_19.","journal-title":"J Cancer Res Therapeutics"},{"key":"1597_CR20","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2017.1373218","author":"Y Liu","year":"2017","unstructured":"Liu Y. Leptomeningeal carcinomatosis from gastric cancer successfully treated by the intrathecal methotrexate plus temozolomide and simultaneous radiotherapy: Case report and literatures review. Cancer Biol Ther. 2017. https:\/\/doi.org\/10.1080\/15384047.2017.1373218.","journal-title":"Cancer Biol Ther"},{"key":"1597_CR21","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.55.5129","author":"T Yamasaki","year":"2016","unstructured":"Yamasaki T, Fukui H, Sei H, et al. Efficacy of intrathecal MTX\/Ara-C combined with systemic chemotherapy in a gastric cancer patient with meningeal carcinomatosis - pubmed. Int Med. 2016. https:\/\/doi.org\/10.2169\/internalmedicine.55.5129.","journal-title":"Int Med"},{"key":"1597_CR22","doi-asserted-by":"publisher","DOI":"10.15386\/mpr-1654","author":"TR Moldovan","year":"2022","unstructured":"Moldovan TR, C\u0103inap C, Fekete Z, et al. Signet ring cell gastric carcinoma with breast and leptomeningeal metastases: a case report. Med Pharm Rep. 2022. https:\/\/doi.org\/10.15386\/mpr-1654.","journal-title":"Med Pharm Rep"},{"key":"1597_CR23","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v10.i1.56","author":"P Kountourakis","year":"2018","unstructured":"Kountourakis P, Papamichael D, Haralambous H, et al. Leptomeningeal metastases originated from esophagogastric junction\/gastric cancer: A brief report of two cases. World J Gastrointes Oncol. 2018. https:\/\/doi.org\/10.4251\/wjgo.v10.i1.56.","journal-title":"World J Gastrointes Oncol."},{"key":"1597_CR24","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.26658","author":"Z Falk","year":"2022","unstructured":"Falk Z, Bou Nasif M, Fallouh N. Ophthalmoplegia in a Her2+ and \u03b2-hCG+ patient with leptomeningeal carcinomatosis secondary to gastric adenocarcinoma. Cureus. 2022. https:\/\/doi.org\/10.7759\/cureus.26658.","journal-title":"Cureus."},{"key":"1597_CR25","doi-asserted-by":"publisher","DOI":"10.1007\/s13691-019-00373-7","author":"M Kano","year":"2019","unstructured":"Kano M, Hihara J, Hirabayashi N, Sueda T. A case of leptomeningeal carcinomatosis in advanced gastric adenocarcinoma with controlled peritoneal dissemination. Int Cancer Conf J. 2019. https:\/\/doi.org\/10.1007\/s13691-019-00373-7.","journal-title":"Int Cancer Conf J."},{"issue":"4","key":"1597_CR26","doi-asserted-by":"publisher","first-page":"732","DOI":"10.3390\/cancers13040732","volume":"13","author":"M Dankner","year":"2021","unstructured":"Dankner M, Lam S, Degenhard T, Garzia L, Guiot M-C, Petrecca K, Siegel PM. The underlying biology and therapeutic vulnerabilities of leptomeningeal metastases in adult solid cancers. Cancers. 2021;13(4):732. https:\/\/doi.org\/10.3390\/cancers13040732.","journal-title":"Cancers"},{"key":"1597_CR27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12987-017-0070-5","volume":"14","author":"C Conrad","year":"2017","unstructured":"Conrad C, Dorzweiler K, Miller MA, et al. Profiling of metalloprotease activities in cerebrospinal fluids of patients with neoplastic meningitis. Fluids Barriers CNS. 2017;14:22. https:\/\/doi.org\/10.1186\/s12987-017-0070-5.","journal-title":"Fluids Barriers CNS"},{"key":"1597_CR28","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-023-04519-9","author":"JH Wijaya","year":"2023","unstructured":"Wijaya JH, Patel UD, Quintero-Consuegra MD, et al. Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis - PubMed. J Neuro-Oncol. 2023. https:\/\/doi.org\/10.1007\/s11060-023-04519-9.","journal-title":"J Neuro-Oncol."},{"key":"1597_CR29","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdad002","author":"Y Nakasu","year":"2023","unstructured":"Nakasu Y, Deguchi S, Nakasu S, et al. Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis - PubMed. Neuro-Oncol Adv. 2023. https:\/\/doi.org\/10.1093\/noajnl\/vdad002.","journal-title":"Neuro-Oncol Adv"},{"key":"1597_CR30","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2010.6.1.33","author":"SJ Kang","year":"2010","unstructured":"Kang SJ, Kim KS, Ha YS, et al. Diagnostic value of cerebrospinal fluid level of carcinoembryonic antigen in patients with leptomeningeal carcinomatous metastasis. J Clin Neurol. 2010. https:\/\/doi.org\/10.3988\/jcn.2010.6.1.33.","journal-title":"J Clin Neurol"},{"key":"1597_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010119","author":"AA Khosla","year":"2023","unstructured":"Khosla AA, Saxena S, Ozair A, Venur VA, Peereboom DM, Ahluwalia MS. Novel therapeutic approaches in neoplastic meningitis. Cancers. 2023. https:\/\/doi.org\/10.3390\/cancers15010119.","journal-title":"Cancers"},{"key":"1597_CR32","doi-asserted-by":"publisher","DOI":"10.18926\/AMO\/62781","author":"R Ino","year":"2021","unstructured":"Ino R, Sada K-E, Miyauchi A, et al. Added Diagnostic value of cerebrospinal fluid carcinoembryonic antigen in a patient with leptomeningeal carcinomatosis as the initial manifestation of gastric cancer - pubMed. Acta Med Okayama. 2021. https:\/\/doi.org\/10.18926\/AMO\/62781.","journal-title":"Acta Med Okayama"},{"key":"1597_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.821594","author":"W Yu","year":"2022","unstructured":"Yu W, Liu Y, Zhao Y, et al. Deep learning-based classification of cancer cell in leptomeningeal metastasis on cytomorphologic features of cerebrospinal fluid. Front Oncol. 2022. https:\/\/doi.org\/10.3389\/fonc.2022.821594.","journal-title":"Front Oncol"},{"key":"1597_CR34","unstructured":"Leptomeningeal Metastases. Central Nervous System Cancers. 1.2024 ed. National Comprehensive Cancer Network; 2024. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/cns.pdf"},{"key":"1597_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70034-6","author":"P Beauchesne","year":"2010","unstructured":"Beauchesne P. Intrathecal chemotherapy for treatment of leptomeningeal dissemination of metastatic tumours - PubMed. Lancet Oncol. 2010. https:\/\/doi.org\/10.1016\/S1470-2045(10)70034-6.","journal-title":"Lancet Oncol"},{"issue":"4","key":"1597_CR36","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1158\/1078-0432.CCR-04-1807","volume":"11","author":"SS Jacobs","year":"2005","unstructured":"Jacobs SS, Fox E, Dennie C, Morgan LB, McCully CL, Balis FM. Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates. Clin Cancer Res. 2005;11(4):1669\u201374. https:\/\/doi.org\/10.1158\/1078-0432.CCR-04-1807.","journal-title":"Clin Cancer Res"},{"issue":"7","key":"1597_CR37","first-page":"1735","volume":"33","author":"RS Bourke","year":"1973","unstructured":"Bourke RS, West CR, Chheda G, Tower DB. Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res. 1973;33(7):1735\u201346.","journal-title":"Cancer Res"},{"issue":"16","key":"1597_CR38","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1182\/blood.2021014506","volume":"139","author":"MR Wilson","year":"2022","unstructured":"Wilson MR, Eyre TA, Kirkwood AA, et al. Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients. Blood. 2022;139(16):2499\u2013511. https:\/\/doi.org\/10.1182\/blood.2021014506.","journal-title":"Blood"},{"key":"1597_CR39","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-020-03555-z","author":"R Malani","year":"2020","unstructured":"Malani R, Fleisher M, Kumthekar P, et al. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer - PubMed. J Neuro-Oncol. 2020. https:\/\/doi.org\/10.1007\/s11060-020-03555-z.","journal-title":"J Neuro-Oncol."},{"key":"1597_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25860-5","author":"SM Prakadan","year":"2021","unstructured":"Prakadan SM, Alvarez-Breckenridge CA, Markson SC, et al. Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases. Nat Commun. 2021. https:\/\/doi.org\/10.1038\/s41467-021-25860-5.","journal-title":"Nat Commun"},{"key":"1597_CR41","doi-asserted-by":"publisher","DOI":"10.21037\/tcr.2019.09.27","author":"JH Cho","year":"2019","unstructured":"Cho JH, Kim SY, Lee J, et al. Detection of circulating tumor cells (CTCs) in cerebrospinal fluid of a patient with HER2-overexpressing gastric cancer and single cell analysis of intra-patient heterogeneity of CTCs. Translat Cancer Res. 2019. https:\/\/doi.org\/10.21037\/tcr.2019.09.27.","journal-title":"Translat Cancer Res."}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01597-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-025-01597-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-025-01597-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T09:28:24Z","timestamp":1744450104000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-025-01597-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["1597"],"URL":"https:\/\/doi.org\/10.1007\/s10120-025-01597-8","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"assertion":[{"value":"1 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2025","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 authors have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}