Preliminary findings of German-sourced ONC201 treatment in H3K27 altered pediatric pontine diffuse midline gliomas.

PURPOSE: H3K27 altered pediatric pontine diffuse midline gliomas (pDMG) have a poor prognosis, and conventional treatments offer limited benefits. However, recent advancements in molecular evaluations and targeted therapies have shown promise. The aim of this retrospective analysis was to evaluate the effectiveness of German-sourced ONC201, a selective antagonist of dopamine receptor DRD2, for the treatment of pediatric H3K27 altered pDMGs. METHODS: Pediatric patients with H3K27 altered pDMG treated between January 2016 and July 2022 were included in this retrospective analysis. Tissue samples were acquired from all patients via stereotactic biopsy for immunohistochemistry and molecular profiling. All patients received radiation treatment with concurrent temozolomide, and those who could acquire GsONC201 received it as a single agent until progression. Patients who could not obtain GsONC201 received other chemotherapy protocols. RESULTS: Among 27 patients with a median age of 5.6 years old (range 3.4-17.9), 18 received GsONC201. During the follow-up period, 16 patients (59.3%) had progression, although not statistically significant, the incidence of progression tended to be lower in the GsONC201 group. The median overall survival (OS) of the GsONC201 group was considerably longer than of the non-GsONC201 group (19.9 vs. 10.9 months). Only two patients receiving GsONC201 experienced fatigue as a side effect. 4 out of 18 patients in the GsONC201 group underwent reirradiation after progression. CONCLUSION: In conclusion, this study suggests that GsONC201 may improve OS in pediatric H3K27-altered pDMG patients without significant side effects. However, caution is warranted due to retrospective design and biases, highlighting the need for further randomized clinical studies to validate these findings.

At what speed does spinal degeneration gear up?: Aging Paradigm in patients with Low Back Pain.

OBJECTIVE: Aging is a cause of spinal degeneration. However, the natural history of degeneration process is unclear. We aimed to analyze change of intervertebral disc degeneration (IVDD) and Modic changes in Caucasians with LBP decade by decade. We also aimed to find out breaking points of having severe IVDD and Modic changes throughout human life. PATIENTS AND METHODS: We conducted a cross-sectional analysis of a retrospective database in patients aged between 10 and 100 years. All patients were evaluated in terms of IVDD and Modic changes. Optimal binning was conveyed to group age of the patients in terms of major changes in percentages of severe IVDD and Modic changes. RESULTS: We evaluated 2434 patients (female: 1328 and male: 1106; mean age: 47.2 ± 17.2 years; age range = 10-98 years). In all patients, 50.5% and 23.6% had severe IVDD and Modic changes at any lumbar level, respectively. Women were significantly more likely to have severe IVDD than men. Frequency of Modic changes at any lumbar level significantly increased in 40 s and 60 s, whereas frequency of severe IVDD at any lumbar level significantly increased in 20 s, 30 s, 50 s and 70 s CONCLUSION: Spinal degeneration had specific gear-up periods in human life. Age groups of future spine studies could be defined according to the new defined change periods of severe IVDD and Modic changes in human life.