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Record W4309018548 · doi:10.1093/neuonc/noac209.588

PATH-15. THE PROGNOSTIC IMPLICATION OF MGMT PROMOTER METHYLATION IN IDH-MUTANT GLIOMAS

2022· article· en· W4309018548 on OpenAlexaff
Gilbert Youssef, Elisa Aquilanti, Alona Muzikansky, Julie J. Miller, Jayne Vogelzang, Emily Lapinskas, Mary Jane Lim-Fat, Rifaquat Rahman, Rameen Beroukhim, Wenya Linda Bi, Ugonma Chukwueke, L. Nicolas Gonzalez Castro, Eudocia Q. Lee, J Ricardo McFaline-Figueroa, Lakshmi Nayak, David A. Reardon, Keith L. Ligon, Patrick Y. Wen

Bibliographic record

VenueNeuro-Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsHealth Sciences CentreUniversity of TorontoSunnybrook Health Science Centre
Fundersnot available
KeywordsOligodendrogliomaCDKN2AAstrocytomaGliomaOncologyMedicineMethylationIDH1Internal medicineUnivariate analysisCancer researchBiologyMultivariate analysisMutantCancerGene

Abstract

fetched live from OpenAlex

Abstract BACKGROUND MGMT promoter methylation in IDH-mutant gliomas was associated with improved survival in a recent study (PMID 35386566) but did not account for the updated WHO classification of CNS tumors. We evaluated the prognostic value of MGMT methylation in IDH-mutant gliomas incorporating the 2021 WHO classification. METHODS We retrospectively identified 431 patients with IDH-mutant gliomas treated at a single institution from 2010-2020. Kaplan-Meier method was used to estimate OS and PFS rates. Log-Rank test was used to evaluate differences between groups. RESULTS Median age was 36.2 years. MGMT promoter was methylated in 49.6%, unmethylated in 17.2%, partially methylated in 6.7%, and untested in 26.5%. Histological diagnosis was consistent with astrocytoma in 45.7%, oligodendroglioma in 33.9%, glioblastoma in 16.4%, and oligoastrocytoma in 4%. After accounting for 1p/19q and CDKN2A statuses, 190 patients had an integrated diagnosis of astrocytoma, grade 2 or 3; 94 had astrocytoma, grade 4; and 147 had oligodendroglioma, grade 2 or 3. There were 101 death events. Median OS was 33.36 years and median PFS was 5.67 years in MGMT methylated gliomas, compared to median OS of 12.54 years (p=0.0064) and median PFS of 3.91 years (p=0.0034) in unmethylated tumors. Upon univariate subgroup analysis, MGMT methylation was associated with significantly longer OS in histological astrocytomas, grade 2 or 4. However, when stratifying patients according to 2021 WHO classification of CNS tumors, there was no significant difference in OS between MGMT methylated and unmethylated astrocytomas or oligodendrogliomas, irrespective of WHO grade. CONCLUSION MGMT promoter methylation was associated with prolonged OS in histological astrocytomas, IDH-mutant. However, MGMT status did not impact survival after incorporating 2021 WHO classification of CNS tumors, suggesting that 1p/19q co-deletion and CDKN2A homozygous deletion are stronger prognostic factors in our cohort. The number of survival events was limited; larger datasets are required for more definitive conclusions.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.023
GPT teacher head0.306
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2022
Admission routes1
Has abstractyes

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