Phase I trial of convection-enhanced delivery of IL13-Pseudomonas toxin in children with diffuse intrinsic pontine glioma

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In Brief

This article reports the results of a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via convection-enhanced delivery into tumors in 5 pediatric patients with diffuse intrinsic pontine glioma. Clinical safety, imaging, and outcome methods from this trial could be used in future clinical trials.

ABBREVIATIONS CED = convection-enhanced delivery; DIPG = diffuse intrinsic pontine glioma; IL-13 = interleukin 13; IL13R = IL-13 receptor; IPI = Impact of Pediatric Illness; KPS = Karnofsky Performance Status; LPS = Lansky Performance Status; MRS = MR spectroscopy; NAA = n-acetyl aspartate; QOL = quality of life; Vd = volume of distribution; Vi = volume of infusion.

Article Information

Correspondence John D. Heiss: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

INCLUDE WHEN CITING Published online December 7, 2018; DOI: 10.3171/2018.9.PEDS17225.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    Second infusion in patient 5. Intraoperative coronal (A) and sagittal-oblique (B) T1-weighted MR images demonstrating retrograde flow of infusate back into the old cannula tract from the infusion 4 weeks prior.

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    Patient 3. Sagittal contrast-enhanced T1-weighted MR images obtained preoperatively (A) and 1 month (B) and 2 (C) and 3 (D) months postoperatively. The 1-month follow-up image (B) shows minimal enhancement, low perfusion, and necrosis at the infusion site consistent with treatment response.

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    Patient 5. Sagittal contrast-enhanced T1-weighted MR images obtained preoperatively (A) and 1 month (B) and 2 (C) and 3 (D) months postoperatively. The 1-month follow-up image (B) shows minimal enhancement, low perfusion, and necrosis at the infusion site consistent with treatment response.

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    Patient 5. MRS findings. A: Before initial infusion: NAA/creatine (Cr) ratio of 0.60, choline (Cho)/Cr ratio of 4.47, and Cho/NAA ratio of 7.44. B: One month postoperatively: NAA/Cr ratio of 10.4, Cho/Cr ratio of 38.3, and Cho/NAA ratio of 3.68. C: Three months postoperatively: NAA/Cr ratio of 0.31, Cho/Cr ratio of 2.76, and Cho/NAA ratio of 8.93.

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    Patient 2. Intraparenchymal air effects on infusate distribution. A–F: Serial axial T1-weighted MR images obtained every 50 minutes, demonstrating the impact of an intraparenchymal air bubble (hypointensity) introduced at the start of the infusion. While there was a small decrease in the volume of air over time, the serial images demonstrate the restriction of anteromedial spread of infusate (hyperintensity) by the air in the parenchyma.



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