Focused Ultrasound-Mediated Blood-Brain Barrier Opening Enhances Panobinostat Efficacy in a Murine Diffuse Intrinsic Pontine Glioma Model

Abstract

AAPM TG 132. The mean score was below 1.0 for all volumes. Editing thecal sac and vertebrae auto contours only required 1 min or less for all patients. The models reduced contouring time by 84 and 40 min for thecal sac and vertebrae, respectively. Conclusion:The deep-learning models provided high-quality auto contours, directly acceptable for lungs and requiring only minor editing in less than one min for thecal sac, vertebrae and kidneys. Given the labor-intensive nature of manually contouring thecal sac and vertebrae, the high accuracy of the auto contours resulted in substantial reduction of contouring time and thus faster turnaround for CSI treatment. The models can provide a uniform starting point for CSI contouring in our field, which is particularly beneficial to clinics with less experiences.

Therapeutic HDAC inhibition in hypermutant diffuse intrinsic pontine glioma

“…Preclinical studies remain limited by the ability of HDACis to consistently traffic across the blood-brain barrier and into tumor, particularly into the pons and it is a limitation of this study to rely on flank model systems, though we believe this does support biological anti-tumor activity of the drug in vivo . The observed efficacy of quisinostat in this study further supports generation of blood-brain penetrating versions of quisinostat as well as continued development of drug conjugates and enhanced locoregional delivery systems such as intra-ommaya approaches used in locoregional CAR T cell trials [42] , intra-pontine approaches used in convention-enhanced delivery (CED) trials [43] or strategies to increase the permeability of the blood-brain barrier to enhance penetrance of HDACi [44] . Other preclinical work has shown benefit of blood brain barrier penetrant quisinostat [45 , 46] and hopefully can be preclinically evaluated in future orthotopic xenograft and genetically-induced models of DIPG.…”

MRI-Guided Focused Ultrasound Blood-Brain Barrier Opening Increases Drug Delivery and Efficacy in a Diffuse Midline Glioma Mouse Model

“…Several groups have looked into this technology to deliver drugs to solid tumors. Some of these trials have shown increased survival and reduced tumor growth 23,35,[48][49][50][51][52][53][54][55][56][57] 54,57,58 .…”

“…As a consequence, this technology has been translated into clinical trials showing the safety of FUS/MB treatments, and current clinical trials are focused on efficacy with tumor types other than DIPG, including glioblastomas. Due to the depth and targeting complexity of the brainstem, only a few groups have investigated using this technology for pontine DMG54,55,[57][58][59] . Over the last 5 years, two groups have looked into using MRI-guided FUS/…”