Abstract
Diffuse midline gliomas harboring the H3 K27M mutation—including the previously named diffuse intrinsic pontine glioma (DIPG)—are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions. The challenge in treating this deadly disease relies on effective delivery of a therapeutic agent to the bulk tumor as well as infiltrating cells. Therefore, methods that can enhance drug delivery to the brain are of great interest. Convection-enhanced delivery (CED) is a strategy that bypasses the BBB entirely and enhances drug distribution by applying hydraulic pressure to deliver agents directly and evenly into a target region. This technique reliably distributes infusate homogenously through the interstitial space of the target region and achieves high local drug concentrations in the brain. Moreover, recent studies have also shown that continuous delivery of drug over an extended period of time is safe, feasible, and more efficacious than standard single session CED. Therefore, CED represents a promising technique for treating midline tumors with the H3K27M mutation.
Highlights
Clinical Presentation of Diffuse Intrinsic Pontine Glioma (DIPG)Primary pediatric brain tumors are rare entities, with an incidence of ∼2,200 cases annually [1,2,3]
Diffuse intrinsic pontine glioma (DIPG), which makes up ∼20% of these primary pediatric primary brain tumors, carries among the direst prognosis [4, 5]
In the largest study of classically defined DIPG tumors that have been biopsied in the molecular era (91 patients), researchers in France found all but one tumor had either a somatic mutation in H3K27M and/or loss of H3K27 trimethylation, highlighting the importance of histone H3 in the pathology of this disease [10]
Summary
Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges. The challenge in treating this deadly disease relies on effective delivery of a therapeutic agent to the bulk tumor as well as infiltrating cells. Convection-enhanced delivery (CED) is a strategy that bypasses the BBB entirely and enhances drug distribution by applying hydraulic pressure to deliver agents directly and evenly into a target region. This technique reliably distributes infusate homogenously through the interstitial space of the target region and achieves high local drug concentrations in the brain. CED represents a promising technique for treating midline tumors with the H3K27M mutation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
