ID #645 Clinical Trials for Diffuse Intrinsic Pontine Glioma and Diffuse Midline Gliomas: A Systematic Review

Background Diffuse intrinsic pontine gliomas (DIPG) and diffuse midline gliomas (DMG) are rare tumors, predominantly affecting children, that are universally fatal despite decades of clinical investigation. Numerous clinical trials have been conducted, yet a modern comprehensive analysis of published trial results has not been completed. Methods PubMed, Web of Science, Scopus, and Global Index Medicus were searched using the terms “diffuse intrinsic pontine glioma” and “diffuse midline glioma.” Clinical trials were included for analysis if they enrolled patients ≤21 years of age with DIPG or DMG and reported outcomes in a peer-reviewed manuscript between 2005 and 2025. Data extracted included trial design, population characteristics, treatment modalities, trial endpoints, and outcomes. Results Of 7,910 studies screened, 77 studies met inclusion criteria. Most trials evaluated upfront therapy (46/77, 60%), with fewer conducted in the relapsed setting (18/77, 23%) or including both (13/77, 17%). The majority were conducted in the United States (46/77, 60%) and were early-phase studies (Phase I: 32/77, 42%; Phase II: 25/77, 32%). Median reported ages at enrollment ranged from 4.2 to 30 years, with wide variability in sex distribution (16.7–100% male). The median number of enrolled patients on these trials was 19 (range 3-253). Biopsy was not required for enrollment in most trials (58/77, 75%). Treatment strategies included adjuvant cytotoxic chemotherapy (22/77, 29%), targeted therapy (29/77, 38%), immunotherapy (12/77, 16%), combination approaches (9/77, 12%), and novel radiotherapy approaches (5/77, 6%). Primary endpoints were heterogeneous, most commonly overall survival and progression-free survival. Only 16/77 studies (21%) incorporated quality-of-life measures. Conclusions Two decades of recent DIPG/DMG trials have been dominated by small, early-phase, heterogeneous studies with limited incorporation of patient-centered outcomes. These findings underscore the need for harmonized trial design, consistent endpoint selection, and greater emphasis on biologically informed and quality-of-life–focused approaches.