Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

Abstract

Introduction Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. Methods Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. Results Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. Conclusion This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

Development of a human in vitro blood–brain tumor barrier model of diffuse intrinsic pontine glioma to better understand the chemoresistance

“…Indeed, patients with DIPG are not eligible for surgical resection due to the anatomic location and the diffuse pattern of the tumor. Moreover, as chemotherapy has failed to show any benefit [3], the standard of care remains focal radiotherapy [4], which provides only temporary relief [5]. Despite the numerous clinical trials held on high-grade glioma (HGG), many of them were inconclusive because of the persistent assumption that pediatric HGGs are similar to their adult counterparts.…”

Personalized Treatment of H3K27M-Mutant Pediatric Diffuse Gliomas Provides Improved Therapeutic Opportunities

“…To date, focal irradiation therapy remains the mainstay of therapy for H3K27M glioma, resulting in improved overall survival rates (11). Although additional systemic therapy is generally considered as beneficial (7,12), no therapy regimen has yet been shown to exert superior effects (11,(13)(14)(15). Consequently, novel, improved therapeutic strategies for H3K27M glioma are needed.…”

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

“…Only forty percent of the pHGGs originated from cerebral hemispheres and the remaining 60% are located in the midline (half in the brainstem and pons and half in the thalamus) [2]. The common standard protocol to treat hemispheric pHGG is largely inspired by adult glioblastomas and starts with surgical resection of the tumor, followed by radiotherapy and chemotherapy [3][4][5].…”