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

Clicks: 51
ID: 321888
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #34 of 289 articles by views in journal of neuro-oncology

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 289 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
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.
Reference Key
openalex_W7170087365 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Benison Lau, Diala P Ajaero, Benjamin A. Hoff, Ashley Pearson, Peter Sajjakulnukit, Jack Wadden, Tiffany Adam, Sunjong Ji, Adam L. Green, Ali Nabavizadeh, Yue Cao, M Aryal, Santhosh Upadhyaya, Andrea Franson, Stefanie Galbán, Sriram Venneti, Bryan Federowicz, Mark Shapiro, Timothy J. Stuhlmiller, Costas Lyssiotis, Craig J Galban, Hemant A Parmar, Mohannad Ibrahim, Carl Koschmann
Are you one of these authors? Claim your profile
Journal journal of neuro-oncology
Year 2026
DOI
10.1093/neuonc/noag164
URL
https://doi.org/10.1093/neuonc/noag164
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.