{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:41:48Z","timestamp":1789764108325,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI","award":["R43CA281429"],"award-info":[{"award-number":["R43CA281429"]}]},{"name":"NCI","award":["R44NS135792"],"award-info":[{"award-number":["R44NS135792"]}]},{"name":"NINDS","award":["R43CA281429"],"award-info":[{"award-number":["R43CA281429"]}]},{"name":"NINDS","award":["R44NS135792"],"award-info":[{"award-number":["R44NS135792"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The blood\u2013brain barrier and blood-CSF barrier limit the uptake of CNS-targeted therapeutics, warranting utilization of intra-cerebrospinal fluid (CSF) drug delivery. Here we review and compare the safety and distribution of different intra-CSF delivery methods reported in clinical literature. Methods: A retrospective literature review of three common CSF access methods was performed. A search consisting of clinical trials published on PubMed from 2000\u20132024 using the following search terms\u2014intracerebroventricular\/intraventricular\/ICV, intrathecal\/IT, intralumbar\/lumbar puncture, cisterna magna\/ICM\/IT-CM, drug delivery, drug administration, and CSF\u2014yielded 38 intracerebroventricular (ICV), 110 lumbar intrathecal (LIT), and six intra-cisterna magna (ICM) studies. Results: After final exclusion criteria were applied, there were 12 ICV, two LIT, and zero ICM publications remaining for analysis. ICV-specific safety was addressed in 11 ICV publications, with headache, nausea, and vomiting being among the most frequently mentioned procedure-associated adverse events (AEs). LIT-specific safety was provided in only one of the two studies, reporting mostly grade 1\/2 AEs but also an instance of grade 4 myelosuppression. For clinical efficacy, progression-free survival (PFS), overall survival (OS), and disease progression rates were largely variable across studies. Pharmacokinetics were analyzed in four ICV studies. Conclusions: The safety profiles of both ICV and LIT injections are acceptable, showing mostly mild to moderate procedure-associated AEs and less common treatment-related AEs than systemically administered therapies. Additionally, ICV achieves therapeutic goals more consistently than the other intra-CSF delivery methods. To date, there are insufficient data to show dose-related response with intra-CSF delivery. Novel tools are being developed to improve upon intra-CSF delivery that will ideally lead to improved patient outcomes in the near future.<\/jats:p>","DOI":"10.3390\/cancers17081263","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:32:53Z","timestamp":1744169573000},"page":"1263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Retrospective Review of Intra-Cerebrospinal Fluid (CSF) Drug Delivery in CNS Malignancies: Safety, Clinical Efficacy and Pharmacokinetic Profiles of Intracerebroventricular (ICV), Lumbar Intrathecal (LIT), and Intra-Cisterna Magna (ICM) Injections"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-8021","authenticated-orcid":false,"given":"Grace Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcie A.","family":"Glicksman","sequence":"additional","affiliation":[{"name":"EnClear Therapies, Newburyport, MA 01950, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajan","family":"Patel","sequence":"additional","affiliation":[{"name":"EnClear Therapies, Newburyport, MA 01950, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5322-5815","authenticated-orcid":false,"given":"Saaz","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Moelis","sequence":"additional","affiliation":[{"name":"EnClear Therapies, Newburyport, MA 01950, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisheka N.","family":"Vanjani","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-0677","authenticated-orcid":false,"given":"Priya","family":"Kumthekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern Memorial Hospital, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Redzic, Z. 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