BIOM-09. PROGNOSTIC AND PREDICTIVE MARKERS FOR OUTCOME IN PATIENTS WITH IDHMT TUMORS TREATED IN THE EORTC CATNON TRIAL ON ADJUVANT AND/OR CONCURRENT TEMOZOLOMIDE IN ANAPLASTIC ASTROCYTOMA
Bibliographic record
Abstract
Abstract INTRODUCTION In a four-arm study, the CATNON trial investigated the role of concurrent and/or adjuvant temozolomide as addition to radiotherapy in anaplastic astrocytoma patients. The results of the final database lock in October 2024 confirmed benefit of adjuvant temozolomide in IDHmt grade 3 astrocytoma patients, without benefit of concurrent temozolomide. We present the prognostic and predictive molecular analyses of the 444 randomized astrocytoma-IDHmt patients. METHODS Glioma relevant DNA alterations were assessed using dedicated next generation sequencing panels. Genome-wide DNA methylation profiling was performed with the HumanMethylationEPIC beadchip., Tumors were graded by both the Epignostix and the NIH-NCI glioma classifier (astrocytomaIDHmt vs astrocytomaIDHmt high-grade). Two 3-tier methylation-based grading scores were used: Continuous Grading Coefficient (CGC) and Global Methylation Score (GMS). MGMT promoter methylation status was determined using the MGMT-STP27 algorithm. For predictive factor analysis, the outcome of patients in the arm treated with radiotherapy alone was compared to that of patients in the three arms treated with radiotherapy and temozolomide. RESULTS With 10.5 years follow-up, 55% of the IDHmt astrocytoma patients were deceased. PDGFRA gene amplification was associated with worse outcome (HR 3.5 (95% CI 2.2, 5.6) comparable to CDKN2A homozygous deletion (HR 3.6 (95% CI 2.5, 5.1). Grading by the NIH-NCI and the Epignostix classifier were highly correlated, with 10% discrepancy. Both identified a prognostic favorable astrocytoma IDHmt subset (HR 0.37 (95% CI 0.28, 0.49), but CGC and GMS were stronger prognosticators in multivariate analysis. Additional prognostic alterations with lower HR include LOH PTEN locus, total Copy Number Variation and CDK4 amplification. MGMT promoter methylation was not prognostic. None of the prognostic molecular factors was predictive for benefit to temozolomide. DISCUSSION PDGFR amplification is equally prognostic to HD-CDKN2A. Methylation-based grading identifies clinically relevant prognostic subgroups. Assessment of MGMT promoter status in these tumors has neither prognostic nor predictive 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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".