Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma

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  • 1 Department of Neurological Surgery, NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York;
  • 2 Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York;
  • 3 Brainlab AG, Munich, Germany; and
  • 4 Departments of Neurosurgery and
  • 5 Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York
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OBJECTIVE

While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors 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.

METHODS

Patients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software 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.

RESULTS

Seven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean ± SD]: 2.66 ± 0.35 vs 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 workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.

ABBREVIATIONS BBB = blood-brain barrier; CED = convection-enhanced delivery; CTCAE = Clinical Terminology Criteria for Adverse Events version 4.0; DIPG = diffuse intrinsic pontine glioma; Vd = volume of distribution determined by the PET signal; Vi = volume of infusion.

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Contributor Notes

Correspondence Mark M. Souweidane: Cornell University, Weill Medical College, New York, NY. mmsouwei@med.cornell.edu.

INCLUDE WHEN CITING Published online September 25, 2020; DOI: 10.3171/2020.6.PEDS20280.

E.D.B. and A.D.R. contributed equally to this work.

Disclosures Memorial Sloan Kettering Cancer Center has institutional financial interests related to this research in the form of intellectual property rights and equity interests in Y-mAbs, the company licensing the intellectual property from Memorial Sloan Kettering Cancer Center. Omburtamab was licensed to Y-mAbs Therapeutics in 2015. This clinical trial was sponsored by Y-mAbs Therapeutics since 2017. Ms. Wembacher-Schroeder and Dr. Thomson are employees of Brainlab.

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