Dataset Information

Convection-Enhanced Delivery.

ABSTRACT: Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood-brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to deliver a variety of therapeutic compounds for a diversity of diseases, including malignant gliomas, Parkinson's disease, and Alzheimer's disease. While a number of technological advances have been made since its development in the early 1990s, clinical trials with CED have been largely unsuccessful, and have illuminated a number of parameters that still need to be addressed for successful clinical application. This review addresses the physical principles behind CED, limitations in the technique, as well as means to overcome these limitations, clinical trials that have been performed, and future developments.

SUBMITTER: Mehta AM

PROVIDER: S-EPMC5398992 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Convection-Enhanced Delivery.

Mehta A M AM Sonabend A M AM Bruce J N JN

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20170401 2

Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood-brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to del ...[more]

PMID: 28299724

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Project description:Abstract INTRODUCTION While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single dose drug infusions, agents for oncologic therapy require repeated or chronic infusions to maintain therapeutic concentrations. Repeat/chronic CED infusions have rarely been described for oncologic purposes. We report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma (DIPG). METHODS Patients were enrolled in a phase I single center clinical trial using 124I-8H9 monoclonal antibody (124I-Omburtamab, Y-mAbs Therapeutics) administered by CED (NCT01502917). Retrospective chart review was used to assess demographic data, CED infusion data, and post-operative neurologic and surgical outcomes. MRI scans were analyzed using iPlan® Flow software (Brainlab AG, Munich, Germany) for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the Clearpoint imaging software (Clearpoint®, MRI Interventions Inc. Irvine, USA). RESULTS Seven patients underwent two or more sequential CED infusions. No patients experienced deficits Clinical Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater. One patient had persistent grade 2 cranial nerve deficit after a second infusion. No patients experienced hemorrhage or stroke post-operatively. There was a statistically significant decrease in radial error (p= 0.005) and absolute tip error (p=0.008) for infusion two compared to the initial infusion. Sequential infusions did not result in significantly different distribution capacity between the first and second infusion (Vd:Vi ratio: 2.66 ± 0.35 versus 2.42 ± 0.75; p=0.45). CONCLUSIONS This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural work flow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncologic purposes.

Dataset Information

Convection-Enhanced Delivery.

Publications

Convection-Enhanced Delivery.

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