Protocols and safety profile of convection enhanced delivery in pediatric patients: a systematic review

Convection-enhanced delivery (CED) is a developmental drug delivery system enabling direct, intraparenchymal placement of therapeutics that bypass the blood-brain barrier. This systematic review aggregates and outlines the available data surrounding current applications and adverse events of pediatric CED to benchmark safety as protocols expand. A comprehensive search through CINAHL, Cochrane, OVID Medline, and Scopus databases was conducted using a modified PRISMA analysis. After deduplication and screening, final articles were selected for data extraction. Of 108 unique articles, 12 studies met the inclusion criteria, including 162 patients (51% males, 44% females, and 5% not reported). The average age was 8.64 years (range 5-14.1 years). The most common indication for CED was for unresectable high-grade glioma (92%), predominantly diffuse intrinsic pontine glioma (83%). CED also addressed genetic enzyme deficiency (8%). The trans-frontal approach was most common (58%), with single catheter systems employed in 50% of studies. A total of 285 adverse events were reported. The most common included headache (20%), limb weakness (18.2%), Grade 1 cranial nerve deficits (6.3%), and general pain (4.9%). Of 132 CTCAE-graded events, 125 were Grade 1 or Grade 2 (94.7%) and 7 were Grade 3 (5.3%). No Grade 4 or Grade 5 adverse events occurred. This first systematic review of CED of pediatric patients demonstrates that while mild side effects are common, severe adverse events are rare. Multi-institutional and longitudinal data are needed to further define CED's role in pediatric applications. These findings support CED as a viable platform for investigational therapies in treatment-resistant pediatric pathologies.