Adjuvant convection-enhanced delivery for the treatment of brain tumors

Abstract

Background: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies.

Methods: The authors performed a review of the literature for the terms "convection enhanced delivery", "glioblastoma", and "glioma". Selectclinical trials were summarized based on their various biological mechanisms and technological innovation, focusing on more recently publisheddata when possible.

Results: We describe the properties, features and landmark clinical trials associated with convection-enhanced delivery for malignant gliomas.We also discuss future trends that will be vital to CED innovation and improvement.

Conclusion: Efficacy of CED for malignant glioma to date has been mixed, but improvements in technology and therapeutic agents arepromising.

Keywords: Adjuvant; Convection-enhanced delivery; Glioblastoma; Glioma; Treatment.

Fig. 1

Case depiction and artist’s rendition (A) of a convective infusion via stereotactically placed cannula. Infusion of drug mixed with Gd-DTPA allows for tracking of distribution. (B-E) Real-time, serially obtained coronal MR images with hypodense tumor region in the pons (arrows), showing growth of the perfused area, with total tumor coverage obtained in (E). Figure adapted from Lonser et al. 2007 [16]

Fig. 2

Evaluation of infusions without vs with active catheter adjustments during CED to a non-human primate putamen. (A) Axial MR images depicting the entire putamen (green) and the postcommissural sub-region (pink) following two separate deposits of infusate. Infusion volumes are listed in the figure. Final 3-dimensional computation of volume showed 35% final coverage achieved. (B) A single occipital trajectory is shown via MR images, utilizing the infuse-as-you-go method of infusion (sequential images taken, ordered left to right). Both MR image depictions (upper: whole putamen [green] and postcommissural putamen [pink]) and 3D reconstruction views (lower) are shown. The cannula (black line) is advanced in a stepwise fashion after defined volumes of infusate were delivered (100 mL total over 32 min). Improved infusion volume and target coverage can be seen over serial infusions. The cannula tip location is indicated by the colored arrowheads. (C) Axial MR and 3-dimensional reconstruction images depicting final putaminal coverage. The final total was 61% of putamen with 68% of the postcommisural putamen, improved coverage compared to two separate infusions. Figure adapted from Sudhakar et al. 2020 [14]