PATH-11. PROGNOSTIC SIGNIFICANCE OF EPIGENETIC SUBTYPES AND CpGs ASSOCIATED WITH PROGRESSION TO G-CIMP LOW IN THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON
Bibliographic record
Abstract
Abstract BACKGROUND Uncontrolled studies have suggested that methylation-based epigenetic subtypes can be used for prognostication of glioma. We used the prospective randomized CATNON trial to validate the clinical relevance of these epigenetic subtypes. METHODS 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. CNV data and methylation data were derived from Infinium MethylationEPIC arrays. Epigenetic subtyping and risk of progression to G-CIMP low were determined from random forest models and 7 specific CpGs (PMID: 29642018). IDH1/2 status was determined with a glioma-tailored NGS panel. Overall survival (OS) was measured from date of randomization. RESULTS Methylation analysis was performed on 654 tumors: 440 were IDH1/2mt, 204 IDH1/2wt and of 10 IDH1/2 status was unknown; 8 IDH1/2mt were 1p/19q codeleted. Based on methylation, tumors were classified as G-CIMP high (n=409), G-CIMP low (n=19), codel-like (n=18), mesenchymal-like (n=107), classic-like (n=48), and PA-like tumors (n=53). Median OS between these epigenetic subtypes varied considerably: codel-like 9.1 yrs, G-CIMP high 9.5 yrs, G-CIMP low 2.8 yrs, mesenchymal-like 1.3 yrs, classic-like 1.6 yrs, and PA-like 2.8 yrs. The difference in OS of the IDH1/2mt astrocytoma subgroup patients was prominent [G-CIMP low vs G-CIMP high: HR 4.12, 95% CI 2.37-7.19, p < 0.001]. Within the IDH1/2mt G-CIMP high astrocytoma patients, 115 tumors were predicted to have risk of progression to G-CIMP low and patients with such tumors indeed had poorer survival [risk vs no-risk: HR 1.59, 95% CI 1.10-2.31, p = 0.02]. Median OS in G-CIMP high tumors with (n=37) and without (n=366) CDKN2A/B HD was 3.3 yrs versus not reached [p< 0.001], in G-CIMP low tumors it was 1.2 yrs (n=6) versus 4.4 yrs (n=12) [p=0.008]. CONCLUSIONS In IDH1/2mt anaplastic astrocytoma, G-CIMP status and CDKN2A/B HD are of independent 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 | 0.006 | 0.003 |
| 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 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".