title: Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.
abstract: Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.
authors: Department of Surgery, Division of Neurosurgery, Duke university Medical Center, Durham, NC 27710, USA. john.sampson@duke.edu
authors: John H
authors: JH
authors: Sampson
authors: Raghu
authors: R
authors: Raghavan
authors: Martin L
authors: ML
authors: Brady
authors: James M
authors: JM
authors: Provenzale
authors: James E
authors: JE
authors: Herndon
authors: David
authors: D
authors: Croteau
authors: Allan H
authors: AH
authors: Friedman
authors: David A
authors: DA
authors: Reardon
authors: R Edward
authors: RE
authors: Coleman
authors: Terence
authors: T
authors: Wong
authors: Darell D
authors: DD
authors: Bigner
authors: Ira
authors: I
authors: Pastan
authors: María Inmaculada
authors: MI
authors: Rodríguez-Ponce
authors: Philipp
authors: P
authors: Tanner
authors: Raj
authors: R
authors: Puri
authors: Christoph
authors: C
authors: Pedain
mesh_terms: D000328:Adult; D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005098:Exotoxins / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007276:Injections, Intraventricular; D018793:Interleukin-13 / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010865:Pilot Projects; D011993:Recombinant Fusion Proteins; D012680:Sensitivity and Specificity; D012984:Software
chemical_list: D000970:Antineoplastic Agents; D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins