{"doi":"10.1007/s11060-024-04904-y","title":"A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma","abstract":"BACKGROUND: Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients. METHODS: Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified 'personalized' drug volume but fixed concentration of 20 mg/mL of liposomal irinotecan in the first cohort escalating to 40 mg/mL in the second cohort. RESULTS: Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1-4 cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20-680 mg in a total volume of 2-17 ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented. CONCLUSIONS: CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing.","journal":"Journal of Neuro-Oncology","year":2025,"id":510699,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1368453,"name":"Karishma Kumar","orcid":null,"position":1,"is_corresponding":false},{"id":170611,"name":"Krystof Bankiewicz","orcid":null,"position":2,"is_corresponding":false},{"id":330930,"name":"Alastair J. Martin","orcid":"0000-0002-7963-4000","position":3,"is_corresponding":false},{"id":267249,"name":"Mitchel S. Berger","orcid":"0000-0003-1983-4892","position":4,"is_corresponding":false},{"id":238092,"name":"Jennifer Clarke","orcid":"0000-0002-8054-7342","position":5,"is_corresponding":false},{"id":267676,"name":"Jennie Taylor","orcid":"0000-0003-3980-5626","position":6,"is_corresponding":false},{"id":267245,"name":"Nancy Ann Oberheim Bush","orcid":"0000-0001-8302-5008","position":7,"is_corresponding":false},{"id":879030,"name":"Annette M Molinaro","orcid":null,"position":8,"is_corresponding":false},{"id":267246,"name":"Manish K. Aghi","orcid":"0000-0002-2949-2227","position":9,"is_corresponding":false},{"id":88539,"name":"Nicholas Butowski","orcid":"0000-0001-5162-2406","position":10,"is_corresponding":false},{"id":364164,"name":"Kazim Narsinh","orcid":"0000-0002-2019-5461","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:47:50.575618Z","pmid":"39760796","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}