CTNI-23. IDH1/2wt ANAPLASTIC GLIOMAS OF THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON TRIAL: OVERALL SURVIVAL RELATED TO TREATMENT, MGMT STATUS AND MOLECULAR FEATURES OF GLIOBLASTOMA
Bibliographic record
Abstract
Abstract BACKGROUND The phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. Here, we present the molecular analysis of the IDH1/2wt subgroup, and associations between molecular characteristics and patient outcomes. METHODS CNV data and MGMT promoter methylation status were assessed from EPIC methylation array data. IDH1/2 and H3F3A mutation status were determined with a glioma tailored next-generation sequencing panel and TERT promoter mutation status using a SNaPshot assay. Overall survival (OS) was measured from date of randomization. RESULTS Of 654 assessed tumors, 211 (32%) were IDH1/2wt. An H3F3A mutation was present in 14 tumors (K27M: n=10; G34R: n=4). Of the remaining 197 patients, 154 tumors had molecular features of glioblastoma according to cIMPACT-NOW 3 criteria (‘IDH1/2wt astrocytomas WHO IV’), 39 tumors did not (‘IDH1/2wt astrocytomas WHO III’), and 4 had inconclusive molecular data. IDH1/2wt astrocytomas WHO III patients had significantly better survival than WHO IV patients: median OS of 2.83 yrs vs 1.43 yrs respectively [log-rank test: p< 0.001]. Of the 154 IDH1/2wt astrocytoma WHO IV, 55 (36%) were found MGMT promoter methylated. MGMT promoter methylation was prognostic in IDH1/2wt astrocytomas WHO IV patients, with a median OS of 1.86 yrs for methylated vs 1.34 yrs for unmethylated [HR 1.62, p=0.006]. In the IDH1/2wt astrocytomas WHO IV, no effect of concurrent and/or adjuvant TMZ was observed; the HR for OS after RT with any TMZ vs RT alone was 1.31 [95% CI 0.73–2.36, p=0.4] for MGMT promoter methylated and 0.90 [95% CI 0.55–1.45, p=0.7] for unmethylated glioma patients. CONCLUSIONS Our study validated the prognostic value of the cIMPACT-NOW 3 criteria. MGMT promoter methylation is prognostic but not predictive for outcome to TMZ treatment in this cohort of IDH1/2wt anaplastic gliomas with molecular features of glioblastoma.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".