bims-malgli 2026-07-26 papers

Neuro Oncol. 2026 Jul 21. pii: noag164. [Epub ahead of print]

Early increase in apparent diffusion coefficient predicts favorable response to Dordaviprone (ONC201) therapy in H3K27M-mutant diffuse midline glioma.

BACKGROUND: Dordaviprone (ONC201) is the first FDA-approved therapy for H3K27M-mutant diffuse midline glioma (DMG). However, therapeutic response varies among patients, and no imaging biomarkers currently predict long-term benefit. Diffusion-weighted MRI and apparent diffusion coefficient (ADC) obtained during standard clinical imaging reflects tissue cellularity and necrosis, offering potential as an early response indicator.
METHODS: Clinical and imaging data from patients treated with dordaviprone (n = 83) on completed studies underwent centralized neuroradiology review, ADC histogram analysis, and Functional Diffusion Mapping (fDM), which were compared and correlated to CSF tumor DNA (tDNA) and metabolomics when available. Final analysis included 38 patients receiving standardized dordaviprone dosing and treatment schedule.
RESULTS: In the pre-progression cohort, early changes in volumetric or cross-sectional RAPNO criteria were not predictive of overall (OS) or progression-free survival (PFS). Importantly, in patients treated pre-progression with dordaviprone post-radiation, tumors with increased diffusion ADC (reduced cellularity) at cycle 3 demonstrated median OS of 732 days versus 360 days for those with decreased ADC (increased cellularity, p = 0.0149); with corresponding PFS of 334 versus 110 days (p = 0.0132).fDM analysis of spatio-temporal changes of ADC did not correlate with outcomes in a sub-cohort analysis but demonstrated predictive patterns in individual patient time course series. CSF metabolomics stratified by ADC change revealed differences in reductive stress metabolites among dordaviprone responders, linking ADC elevation to dordaviprone -driven metabolic effects.
CONCLUSION: Early increase in ADC correlates with improved response to dordaviprone in H3K27M-DMG and correlates with CSF metabolic changes, suggesting ADC warrants prospective validation as a biomarker.

Keywords: Apparent Diffusion Coefficient; Brain tumor; Diffuse Midline Glioma; Diffuse intrinsic Pontine Glioma; Diffusion-weighted imaging

DOI: https://doi.org/10.1093/neuonc/noag164

J Clin Oncol. 2026 Jul 22. JCO2600191

Corticosteroids in Glioblastoma Management: A Reconsideration of a 65-Year Practice.

Bertrand Liang, Michael Weil.

DOI: https://doi.org/10.1200/JCO-26-00191

Neuro Oncol. 2026 Jul 21. pii: noag163. [Epub ahead of print]

Carboplatin induces optic nerve oligodendrocyte loss and impairs myelin sheath microstructure in a mouse model of neurofibromatosis type 1 (NF1).

Benjamin E Aghoghovwia, Kechen Ban, Dimitrios Stavropoulos, Chi-Yu Chen, Bo Wei, Ava S Hamblett, Samer Sharafaldin, Hana El-Toukhy, Momo Harris, Chhay Hok, Varsha K Chandramouli, Carlos Manuel Martínez Cerda, Renae E Bertrand, Sama Alnassiry, Philip L Lorenzi, David H Gutmann, Kun-Che Chang, Rajasekaran Mahalingam, Yuan Pan.

BACKGROUND: Vision impairment is a significant concern for children with Neurofibromatosis type 1 (NF1)-associated optic pathway glioma (OPG). While carboplatin-containing chemotherapy is often first-line therapy for NF1-OPG, it does not consistently improve visual function. Furthermore, chemotherapy is associated with altered white matter microstructure in individuals with NF1-OPG, suggesting a detrimental effect on oligodendroglia. We analyzed the tumor-independent effects of carboplatin on oligodendrocytes in Nf1-mutant mice and evaluated pharmacological strategies for reducing this chemotherapy-associated toxicity.
METHODS: Carboplatin- or vehicle-treated Nf1+/- mice or Nf1-mutant optic glioma cells were employed to assess the effects of restorative interventions on optic nerve oligodendrocytes in vivo and tumor cell growth in vitro, respectively.
RESULTS: Clinically relevant carboplatin dosing induced oligodendrocyte loss and impaired myelin sheath structure in the optic nerves of Nf1+/- mice, an effect not observed following vinca alkaloids or MEK inhibitor (selumetinib) treatment. Carboplatin downregulates genes essential for cholesterol biosynthesis and decreases cholesterol levels in carboplatin-exposed Nf1+/- optic nerves, such that dietary cholesterol supplementation after carboplatin exposure restored oligodendrocyte numbers. Carboplatin also increases the density of monocytes (microglia/macrophages) in the Nf1+/- optic nerves. Using PLX5622 (a CSF1R inhibitor) to reduce monocytes numbers or using clemastine to promote the generation and survival of oligodendrocytes, alleviated the oligodendrocyte loss caused by carboplatin treatment. Notably, PLX5622 and clemastine reduced the viability of Nf1-mutant optic glioma tumor cells.
CONCLUSIONS: Our findings demonstrate that carboplatin induces oligodendroglial toxicity in Nf1-mutant optic nerves, which can be mitigated by clemastine, PLX5622, or dietary cholesterol following carboplatin exposure.

Keywords: carboplatin; chemotherapy-induced toxicity; neurofibromatosis type 1; oligodendrocytes

DOI: https://doi.org/10.1093/neuonc/noag163