P08.40 The prognostic and predictive value of an explant assay of gliomas in response to temozolomide
Bibliographic record
Abstract
Introduction: Glioblastoma multiforme (GBM) is the most common and lethal primary adult brain tumor, with significant variability in therapeutic response due to its underlying molecular and pathological heterogeneity. This study investigated the prognostic and predictive value of an established explant assay in response to the clinically relevant chemotherapy temozolomide (TMZ). METHODS: 138 patients with pathologically-verified gliomas and ongoing follow-up of clinical outcomes were included in the study. Tumor specimens at the time of resection were plated onto a collagen matrix with and without TMZ. Using photo-microscopy, the migratory distance of invading cells was quantified over 5 days. Results: 111 viable and malignant explant assays were collected in glioma patients with overall survival outcomes available on 80% of them. GBMs showed increased invasiveness compared to anaplastic and grade II gliomas on the assay. Glioma patients whose tumors showed a greater invasive distance on the assay at 5 days had reduced overall survival. Inhibition of invasion by 20% by TMZ on the explant assay predicted the time to recurrence after TMZ treatment and the overall survival of GBM patients. Response in this assay was compared to additional parameters including induction of apoptosis and MGMT methylation status. There was a correlation of 75% with TMZ sensitivity and MGMT methylation. Apoptosis marker caspase was increased in TMZ sensitive tumours by 15 % over non-treated control tumours when examined post-treatment. This increase in caspase was only 5% in non-sensitive tumors. CONCLUSION: This study demonstrates that an explant assay, by reproducing the in vivo environment, can predict overall survival of gliomas patients and response to temozolomide. This study demonstrates that this assay is of individualized prognostic value.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".