MOLECULAR PROFILING TO UNDERSTAND TREATMENT RESISTANCE AND RESPONSE IN GLIOBLASTOMA
Bibliographic record
Abstract
Abstract Patients with glioblastoma experience a wide variation in response to standard treatment, with nearly 30% experiencing tumour progression during treatment, and nearly 7% surviving more than 5 years. CEST-MRI is sensitive to treatment-induced changes in tumour metabolism and can be used to evaluate treatment response, allowing for the differentiation between early and late progressors before treatment initiation. OBJECTIVE: The purpose of this study is to establish genomic and transcriptomic profiles of early and late progressors in patients with glioblastoma who have undergone CEST-MRI. METHODS: Patients (n=25) were imaged with CEST-MRI at multiple time points throughout standard chemoradiation treatment. DNA and RNA were co-extracted from 25 fresh-frozen matched normal and tumour pairs and processed for whole genome sequencing and gene expression analysis using Nanostring. RESULTS: Early progressors (n = 12) and late progressors (n =13) had significant differences in OS and PFS (log rank <0.0001) as well as in gene expression and pathway deregulation. Genes significantly expressed in early progressors compared to late progressors include CCNA1 (p =0.000557), IGFBP3 (p = 0.000602), ASS1 (p = 0.000698), and ID1 (p= 0.000993), which were also prognostic of PFS and OS in a Cox regression model. CONCLUSION: Upon validation in a larger cohort, this data may serve as a radiogenomic biomarker to assess treatment response within early phases of treatment and adapt the treatment plan to individual biology.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".