Convection Enhanced Delivery for Diffuse Intrinsic Pontine Glioma: Review of a Single Institution Experience

Abstract

Diffuse intrinsic pontine gliomas (DIPGs) are a pontine subtype of diffuse midline gliomas (DMGs), primary central nervous system (CNS) tumors of childhood that carry a terrible prognosis. Because of the highly infiltrative growth pattern and the anatomical position, cytoreductive surgery is not an option. An initial response to radiation therapy is invariably followed by recurrence; mortality occurs approximately 11 months after diagnosis. The development of novel therapeutics with great preclinical promise has been hindered by the tightly regulated blood–brain barrier (BBB), which segregates the tumor comportment from the systemic circulation. One possible solution to this obstacle is the use of convection enhanced delivery (CED), a local delivery strategy that bypasses the BBB by direct infusion into the tumor through a small caliber cannula. We have recently shown CED to be safe in children with DIPG (NCT01502917). In this review, we discuss our experience with CED, its advantages, and technical advancements that are occurring in the field. We also highlight hurdles that will likely need to be overcome in demonstrating clinical benefit with this therapeutic strategy.

Convection-Enhanced Delivery In Silico Study for Brain Cancer Treatment

“…Following data from relevant clinical CED studies ( Barua et al, 2013 ; Shi and Sanche, 2019 ; Stine and Munson, 2019 ; Tosi and Souweidane, 2020 ), the infusion flow rate, Q f , ranged from 0.025 to 0.75 ml/h and the infusion volume varied between 0.25 and 185 ml. A flow rate of 0.5 ml/h and an infusion volume of 3 ml were selected for all simulations.…”

Pediatric high‐grade glioma: moving toward subtype‐specific multimodal therapy

“…A phase 1 dose-escalation study evaluating [ 124 I]-8H9 (NCT01502917), a radioimmunotherapy compound targeting B7-H3, in new DIPG patients following radiation established the safety of CED in DIPG. The design of the study precluded formal analysis of survival benefit from the treatment, but a follow-up report showed a preliminary median survival of 17.5 months, a 1-year survival rate of 58.5%, and multiple patients surviving more than 3 years [122,123]. Another phase 1 CED trial for brainstem gliomas utilized ACNU (nimustine hydrochloride) and included six DIPG patients.…”

Childhood Malignant Brain Tumors: Balancing the Bench and Bedside

“…The paradigm shift in understanding of the molecular heterogeneity of pHGG, together with the failure of conventional therapeutics to significantly improve outcomes for several years, has shifted focus towards developing novel agents that manipulate the epigenetic and genomic aberrations inherent in pHGG molecular subgroups, immunotherapies, and the development of alternative drug administration routes to penetrate the blood–brain barrier such as convection enhanced delivery for diffuse midline glioma H3K27 mutant/DIPG [ 92 , 101 , 102 , 103 , 104 , 105 ].…”