Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.
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.
Sampson
John H
JH
Department of Surgery, Division of Neurosurgery, Duke university Medical Center, Durham, NC 27710, USA. john.sampson@duke.edu
Raghavan
Raghu
R
Brady
Martin L
ML
Provenzale
James M
JM
Herndon
James E
JE
Croteau
David
D
Friedman
Allan H
AH
Reardon
David A
DA
Coleman
R Edward
RE
Wong
Terence
T
Bigner
Darell D
DD
Pastan
Ira
I
Rodríguez-Ponce
María Inmaculada
MI
Tanner
Philipp
P
Puri
Raj
R
Pedain
Christoph
C
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
D000970:Antineoplastic Agents; D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D011993:Recombinant Fusion Proteins