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Introduction: Despite much progress, the prognosis for H3K27-altered diffuse midline glioma (DMG), previously known as diffuse intrinsic pontine glioma when located in the brainstem, remains dark and dismal., Areas Covered: A wealth of research over the past decade has revolutionized our understanding of the molecular basis of DMG, revealing potential targetable vulnerabilities for treatment of this lethal childhood cancer. However, obstacles to successful clinical implementation of novel therapies remain, including effective delivery across the blood-brain barrier (BBB) to the tumor site. Here, we review relevant literature and clinical trials and discuss direct drug delivery via convection-enhanced delivery (CED) as a promising treatment modality for DMG. We outline a comprehensive molecular, pharmacological, and procedural approach that may offer hope for afflicted patients and their families., Expert Opinion: Challenges remain in successful drug delivery to DMG. While CED and other techniques offer a chance to bypass the BBB, the variables influencing successful intratumoral targeting are numerous and complex. We discuss these variables and potential solutions that could lead to the successful clinical implementation of preclinically promising therapeutic agents.

Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor. While there are a number of in vivo rodent models for evaluating tumor biology and response to therapy, these models require significant time and resources. Here, we established the chick-embryo chorioallantoic (CAM) assay as an affordable and time efficient xenograft model for testing a variety of treatment approaches for DIPG. We found that patient-derived DIPG tumors develop in the CAM and maintain the same genetic and epigenetic characteristics of native DIPG tumors. We monitored tumor response to pharmaco- and radiation therapy by 3-D ultrasound volumetric and vasculature analysis. In this study, we established and validated the CAM model as a potential intermediate xenograft model for DIPG and its use for testing novel treatment approaches that include pharmacotherapy or radiation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Diffuse intrinsic pontine glioma (DIPG) is a lethal high-grade pediatric brainstem tumor without a cure. Despite numerous clinical trials over the last decades, the prognosis has remained poor. The aim of this update was to report on the status and outcomes of all clinical trials for DIPG performed to better understand the landscape of research efforts for this diagnosis to date., Methods: The ClinicalTrials.gov database was reviewed in May 2019 for all possible interventional clinical trials that included DIPG as a diagnosis of primary investigation. These were then screened against selection criteria to identify pertinent clinical trials., Results: Ninety-five clinical trials satisfied all inclusion criteria, with 55 (58%) trials specific to the DIPG diagnosis only. In terms of the most prevalent design features, 42 (44%) were phase I trials, with median expected start and completion years in 2011 (range, 1994-2020) and 2018 (range, 2005-2047), respectively. Median target number of patients to enroll was 38 (range, 1-1500), and the most common primary outcome was safety and toxicity (56%). There were 69 (73%) trials originating from the USA, with 49 (52%) of them being single institutional. Only 10 (11%) trials have reported results to date., Conclusions: To date, 95 clinical trials investigating DIPG with specific emphasis have been registered on ClinicalTrials.gov. There were only a small number of trials that had study results available, and they uniformly reported non-significant improvement to prognosis. Given the rarity and lethality of DIPG, which limits the accumulation of large cohorts, our results mandate the need for more robust, systematic clinical trial design to minimize redundancies and maximize yield in the future.

Purpose: Although the dismal clinical prognosis of diffuse intrinsic pontine glioma (DIPG) has not changed, there has been significant progress in the academic literature made in the biological understanding of this brainstem tumor. The aim of this analysis was to evaluate citation and other bibliometric characteristics of the 100 most-cited DIPG articles in the current literature in order to better understand the current state of our academic efforts in this area., Methods: Elsevier's Scopus database was searched for the 100 most-cited articles that focussed on DIPG. Articles were dichotomized as either primarily basic science (BSc) or clinical (CL) articles. Various bibliometric parameters were summarized and comparison between BSc and CL articles was performed using Pearson's chi-square and Mann-Whitney U tests., Results: Of the 100 most-cited articles, 36 (36%) were BSc and 64 (64%) were CL articles. Overall median values were as follows: citation count, 52 (range, 27-261); citation rate per year, 8.6 (range, 1.7-104); number of authors, 9 (range, 1-63); and publication year, 2011 (range, 1997-2017). Articles were published in a total of 43 different journals and predominately originated in the USA (n = 67, 67%). When compared with CL articles, BSc articles reported significantly greater citation count (P = 0.03), citations rate per year (P < 0.01), number of authors (P < 0.01), and more recent years of publication (P < 0.01)., Conclusions: The 100 most-cited articles about DIPG were characterized in this analysis. Although smaller in overall proportion, BSc articles demonstrated significantly increased bibliometric parameters, supporting the recent dominance of BSc in this field, primarily involving histone biology of the H3K27M mutation. Moving forward, it will be of great interest to see how the findings of these high-impact BSc articles will translate into future high-impact CL articles.