ArticleNeuro-oncology2022
Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03416530 (ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3 K27M Gliomas), which is not on this map. Cited by 76 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
ONC201 in Newly Diagnosed Diffuse Intrinsic Pontine Glioma and Recurrent/Refractory Pediatric H3 K27M Gliomas
Who cites it
76 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Cerebrospinal fluid ctDNA as a diagnostic and prognostic tool in gliomas: a systematic review and meta-analysis.Frontiers in oncology · 2025Pooled it
- Biopsy of diffuse midline glioma is safe and impacts targeted therapy: a systematic review and meta-analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Pooled it
- Cerebrospinal Fluid biomarkers in pediatric brain tumors: A systematic review.Neoplasia (New York, N.Y.) · 2023Pooled it
- Tumor-derived cell-free DNA detected in cerebrospinal fluid enables minimally invasive profiling of pediatric brain tumors.The Journal of clinical investigation · 2026Trial
- Dynamics of tumor in situ fluid circulating tumor DNA in recurrent glioblastomas forecasts treatment efficacy of immune checkpoint blockade coupled with low-dose bevacizumab.Journal of cancer research and clinical oncology · 2024Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- The DIPG/DMG National Tumor Board: The power of advocacy.Neuro-oncology pediatrics · 2026Article
- Understanding DMG: current treatment options and prospective solutions using nanoparticles.Drug delivery and translational research · 2026Review
- Cerebrospinal fluid cell-free DNA sequencing in pediatric CNS tumors: towards liquid molecular neuropathology.Acta neuropathologica · 2026Review
- ONC206 demonstrates potent antitumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.Neuro-oncology · 2026Article
- Tumor extracellular vesicle RNA profiling predicts treatment response in pediatric diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Extracellular Vesicles in the Biology and Liquid Biopsy Diagnostics of Pediatric High-Grade Glioma - Emerging Findings and Opportunities.Journal of extracellular biology · 2026Review
- Cerebrospinal Fluid in Pediatric Neuro-Oncology: Molecular Diagnosis, Disease Monitoring, and Clinical Translation.International journal of molecular sciences · 2026Review
- Limited reliability of H3K27M detection using a commercially available blood-based comprehensive genomic profiling test in patients with diffuse midline gliomas: analysis of the nationwide C-CAT database in Japan.International journal of clinical oncology · 2026Article
- Diffuse Midline Gliomas: Clinical, Diagnostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors.Nature cancer · 2026Article
- The use of plasma miRNAs to better manage pediatric brain gliomas.Pediatric research · 2026Article
- Circulating miRNAs as potential liquid biomarkers for pediatric gliomas.Pediatric research · 2026Article
- Histologically indolent but widely disseminated diffuse midline glioma H3K27-altered revealed by autopsy.Brain tumor pathology · 2026Article
- The role of dordaviprone in the multidisciplinary management of diffuse midline glioma.Surgical neurology international · 2026Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundDiffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis.
methodsWe conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI).
resultsChange in H3.3K27M VAF over time ("VAF delta") correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF "spikes" (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (>1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression.
conclusionOur work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.