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SURG-09. CORTICOSPINAL TRACT TOLERANCE TO CATHETER POSITIONING FOR CONVECTION ENHANCED DELIVERY IN THE BRAIN STEM

ABSTRACT: Abstract INTRODUCTION Convection enhanced delivery (CED) has recently been explored as a therapeutic strategy for children with diffuse intrinsic pontine glioma (DIPG). An anterior or supratentorial approach for catheter positioning risks conflict with descending white matter bundles where they become concentrated in the internal capsule and crural pyramid. We describe our experience planning catheter trajectories in the context of eloquent structures and outcomes this patient population. METHODS As part of a Phase 1 clinical trial using CED with 124I-8H9, a radiolabeled monoclonal antibody (NCT01502917), a flexible step-design infusion catheter (Brainlab Flexible Catheter, BrainLab, Munich, Germany) was surgically placed via a supratentorial approach. Surgical planning was conducted based on 3D T1, T2, and SWI sequences. A fully compatible MR-guidance platform was used for trajectory planning catheter deployment. A neurologic exam was performed immediately post-procedure, prior to initiating infusion, to assess for procedure-related deficits. Intra- and post-procedural MR images were analyzed for the anatomic position of catheter trajectories. Conflicts between the catheter tract and the posterior limb of the internal capsule and the pyramid of the crus cerebri were recorded. Correlation between motor deficits and the catheter path was evaluated. RESULTS Thirty catheter insertions were performed for children with DIPG. Nine patients (30%) experienced transient hemiparesis associated with drug infusion, but no permanent deficits were identified. The posterior limb of the internal capsule and the pyramid of the crus cerebri frequently overlapped the catheter tract without incident. CONCLUSIONS Transgression of descending corticospinal motor tracts by catheters for intracranial infusion is acceptable. We observed that a supratentorial approach to the brainstem crossing eloquent fibers resulted in one neurologic deficit. There does not appear to be a functional risk requiring a need for avoidance of the dominant motor fiber tracts during trajectory planning.

SUBMITTER: Morgenstern P

PROVIDER: S-EPMC5691955 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Project description:Abstract INTRODUCTION: Convection enhanced delivery (CED) has recently been explored as a therapeutic strategy for children with diffuse intrinsic pontine glioma (DIPG). An anterior or supratentorial approach for catheter positioning risks conflict with descending white matter bundles where they become concentrated in the internal capsule and crural pyramid. We describe our experience planning catheter trajectories in the context of eloquent structures and outcomes this patient population. METHODS: As part of a Phase 1 clinical trial using CED with 124I-8H9, a radiolabeled monoclonal antibody (NCT01502917), a flexible step-design infusion catheter (Brainlab Flexible Catheter, BrainLab, Munich, Germany) was surgically placed via a supratentorial approach. Surgical planning was conducted based on 3D T1, T2, and SWI sequences. A fully compatible MR-guidance platform was used for trajectory planning catheter deployment. A neurologic exam was performed immediately post-procedure, prior to initiating infusion, to assess for procedure-related deficits. Intra- and post-procedural MR images were analyzed for the anatomic position of catheter trajectories. Conflicts between the catheter tract and the posterior limb of the internal capsule and the pyramid of the crus cerebri were recorded. Correlation between motor deficits and the catheter path was evaluated. RESULTS: Thirty-three catheter insertions were performed for 28 children with DIPG. One patient experienced a slight worsening of an existing ipsilateral facial palsy likely related to the course of facial nerve fibers in the brainstem. The posterior limb of the internal capsule and the pyramid of the crus cerebri frequently overlapped the catheter tract without incident. CONCLUSIONS: Transgression of descending corticospinal motor tracts by catheters for intracranial infusion is acceptable. We observed that a supratentorial approach to the brainstem crossing eloquent fibers resulted in one neurologic deficit. There does not appear to be a functional risk requiring a need for avoidance of the dominant motor fiber tracts during trajectory planning.

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.

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SURG-09. CORTICOSPINAL TRACT TOLERANCE TO CATHETER POSITIONING FOR CONVECTION ENHANCED DELIVERY IN THE BRAIN STEM

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