Deformational changes after convection-enhanced delivery in the pediatric brainstem

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>In the brainstem, there are concerns regarding volumetric alterations following convection-enhanced delivery (CED). The relationship between distribution volume and infusion volume is predictably greater than one. Whether this translates into deformational changes and influences clinical management is unknown. As part of a trial using CED for diffuse intrinsic pontine glioma (DIPG), the authors measured treatment-related volumetric alterations in the brainstem and ventricles.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Enrolled patients underwent a single infusion of radioimmunotherapy. Between 2012 and 2019, 23 patients with volumetric pre- and postoperative day 1 (POD1) and day 30 (POD30) MRI scans were analyzed using iPlan<jats:sup>®</jats:sup> Flow software for semiautomated volumetric measurements of the ventricles and pontine segment of the brainstem.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Children in the study had a mean age of 7.7 years (range 2–18 years). The mean infusion volume was 3.9 ± 1.7 ml (range 0.8–8.8 ml). Paired t-tests demonstrated a significant increase in pontine volume immediately following infusion (p &lt; 0.0001), which trended back toward baseline by POD30 (p = 0.046; preoperative 27.6 ± 8.4 ml, POD1 30.2 ± 9.0 ml, POD30 29.5 ± 9.4 ml). Lateral ventricle volume increased (p = 0.02) and remained elevated on POD30 (p = 0.04; preoperative 23.5 ± 15.4 ml, POD1 26.3 ± 16.0, POD30 28.6 ± 21.2). Infusion volume had a weak, positive correlation with pontine and lateral ventricle volume change (r<jats:sup>2</jats:sup> = 0.22 and 0.27, respectively). Four of the 23 patients had an increase in preoperative neurological deficits at POD30. No patients required shunt placement within 90 days.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>CED infusion into the brainstem correlates with immediate but self-limited deformation changes in the pons. The persistence of increased ventricular volume and no need for CSF diversion post-CED are inconsistent with obstructive hydrocephalus. Defining the degree and time course of these deformational changes can assist in the interpretation of neuroimaging along the DIPG disease continuum when CED is incorporated into the treatment algorithm.</jats:p></jats:sec>

Theragnostic Aspects and Radioimmunotherapy in Pediatric Tumors

“…The same research group demonstrated similar results in a previous study [23]. Nevertheless, the main drawback of CED infusion in children with DIPG may be represented by subsequent but self-limited volumetric alterations in the pons [29].…”

Convection-Enhanced Delivery in Children: Techniques and Applications

“…None of the patients required a shunt within 90 days. The infusion volume had a weak positive correlation with the volume change in the pons and lateral ventricles, but changes in pontine volume did not relate to neurological deficits [82]. This study also suggests that an increase in pontine volume in the first month after CED is expected and not representative of tumour progression.…”

“…The deformational changes in the brainstem caused by infusion of fluid into DIPG have been investigated [82]. This is particularly concerning, as the volume of distribution within the pons is greater than the volume of fluid infused, and any increase in pontine swelling can potentially worsen obstructive hydrocephalus or increase pressure on tracts and cranial nerve nuclei.…”

Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities

“…However, due to individual variation, one geometric model cannot be used for another patient. Therefore, obtaining patient-specific models is also a hot topic and has been widely explored [ 38 , 144 , 145 , 146 , 147 ].…”