MPTH-41. MGMT STATUS PREDICTS SURVIVAL OUTCOMES IN NRG ONCOLOGY/RTOG 0424: A PHASE II TRIAL OF TEMOZOLOMIDE-BASED CHEMORADIOTHERAPY FOR HIGH RISK LOW-GRADE GLIOMAS
Bibliographic record
Abstract
This study sought to determine the proportion of patients with MGMT promoter methylation within NRG Oncology/RTOG 0424 and its prognostic significance in the setting of high-risk low-grade glioma treated with radiation and temozolomide. The MGMT-STP27 prediction model was used to calculate MGMT promoter methylation status from Illumina HM-450K data. Univariable (UVAs) and multivariable analyses (MVAs) were performed using the Cox proportional hazard model, to analyze the effect of MGMT status on survival outcomes. Patient pretreatment characteristics were included as covariates in MVAs. Of all the eligible patients in NRG Oncology/RTOG 0424, 75 (58.1%) have MGMT status available: 57 (76.0%) methylated and 18 (24.0%) unmethylated. Between the two groups, no significant difference was observed on age and performance status at baseline. Majority (72.2%) of the unmethylated patients had astrocytoma as opposed to oligoastrocytoma/oligodendroglioma, whereas 40.4% of methylated patients had astrocytoma. Upon UVAs, MGMT methylation was significantly correlated with better OS and PFS. Upon MVAs, the statistical significance was maintained, with a HR=2.89 (p=0.009) for OS and a HR=2.88 (p=0.003) for PFS. MGMT promoter methylation, as determined by the MGMT- STP27 model, was an independent prognostic biomarker of high-risk low-grade glioma treated with temozolomide and radiation. The large percentage of methylated patients in this study may be a contributing factor to the high survival rates reported previously relative to historical controls. Importantly, this is the first study to validate the prognostic significance of MGMT promoter methylation in temozolomide-treated grade II glioma patients using rigorous MVAs with prospectively-collected, well-annotated clinical data. Analysis of the prognostic significance of MGMT promoter methylation relative to IDH and 1p/19q status is ongoing. FUNDING: U10CA21661, U10CA180868, U10CA180822, and U10CA37422 (NCI) & Merck & Co. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).
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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 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".