Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT), which provides transient symptomatic relief and limited survival advantage. Successful implementation of radiosensitization strategies in DMG remains elusive. In this project, we identify Napabucasin, an NAD(P)H Quinone Dehydrogenase 1 (NQO1)-bioactivatable reactive oxygen species (ROS) inducer, as a potent radiosensitizer in DMG both in vitro and in vivo. We show Napabucasin-mediated ROS production and cytotoxicity are dependent on NQO1, and establish the novel safety, feasibility, and survival benefit of convection-enhanced drug delivery (CED) of Napabucasin to circumvent the blood-brain barrier (BBB) concurrent with RT in an orthotopic DMG mouse model. Using this multi-modality strategy, we identify a promising treatment paradigm in DMG that may also be utilized to develop novel therapeutic treatments for other brain tumors.

No description available.

This study examined the relationship between executive and psychosocial functioning in 45 children and adolescents age 6 to 17 years who had been treated for a brain tumor. Executive functioning deficits can profoundly impact an adult's ability to function successfully in life. The purpose of the study was to evaluate the potential impact of executive functioning deficits on the day-to-day functioning in a pediatric population. The domains of executive functioning assessed included cognitive flexibility, conceptual thinking, sustained attention, and response inhibition. Psychosocial functioning was assessed using both parent and child report. Several significant relationships were found for adolescents ages 15 and older, with effect sizes ranging from medium to large. In particular, cognitive flexibility and conceptual thinking were significantly related to parent report of depression and adaptive functioning. Fewer significant relationships with smaller effect sizes were found for younger children. The results may reflect the developmental emergence of executive functioning abilities and late effects of executive functioning deficits upon psychosocial functioning. The correlational design of this study precludes definitive statements regarding the temporal nature of the relationship. Additional research, including longitudinal research and replicatory studies, will be needed to further investigate the developmental consequences of executive functioning impairment.