MGMT promoter methylation in IDH-WT glioblastoma is the strongest validated predictor of...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-MGMT-METHYLATION-GBM |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-GBM |
| Sources | SRC-CIVIC SRC-EANO-GBM-2024 SRC-NCCN-CNS-2025 |
Actionability Facts
| Biomarker | BIO-MGMT-METHYLATION |
|---|---|
| Variant | MGMT promoter methylation (positive vs unmethylated; ~40% of newly-diagnosed glioblastoma IDH-WT) |
| Disease | DIS-GBM |
| ESCAT tier | IA |
| Recommended combinations | Stupp protocol: concurrent RT + temozolomide → 6 cycles adjuvant TMZ (1L MGMT-methylated GBM per SRC-NCCN-CNS-2025, SRC-EANO-GBM-2024), hypofractionated RT + TMZ (elderly ≥65y MGMT-methylated per SRC-EANO-GBM-2024), lomustine + TMZ + RT (alternative MGMT-methylated 1L per CeTeG/NOA-09 — listed as option in SRC-EANO-GBM-2024) |
| Contraindicated monotherapy | TMZ monotherapy without RT in newly-diagnosed GBM (excluding very elderly poor performance per SRC-EANO-GBM-2024) |
| Evidence summary | MGMT promoter methylation in IDH-WT glioblastoma is the strongest validated predictor of temozolomide benefit (Stupp NEJM 2005 / 2009 long-term — methylated patients derive ~2x OS benefit from RT+TMZ vs RT alone). Standard 1L for newly-diagnosed GBM remains Stupp protocol (concurrent RT + temozolomide → 6 cycles adjuvant TMZ) per SRC-NCCN-CNS-2025, SRC-EANO-GBM-2024 — but methylation status drives intensification decisions: in elderly MGMT-methylated patients, hypofractionated RT + TMZ (Perry NEJM 2017) is preferred, while elderly MGMT-unmethylated patients can receive RT alone with much smaller TMZ benefit. CeTeG/NOA-09 (Herrlinger Lancet 2019) showed lomustine + TMZ + RT may extend OS in newly-diagnosed MGMT- methylated GBM but is not standard worldwide. |
Notes
ESCAT IA / OncoKB Level 2 (predictive biomarker; not a target). MGMT testing recommended for ALL newly-diagnosed GBM; methodology = MS-PCR or pyrosequencing; mosaic / weakly-methylated intermediate cases remain therapeutically ambiguous. In MGMT-unmethylated GBM, the benefit of TMZ is small but Stupp remains standard outside of trials per SRC-EANO-GBM-2024 — see notes on contradictions: NCCN does not withhold TMZ from unmethylated patients while EANO 2024 explicitly considers RT-alone an acceptable alternative for unmethylated elderly. This represents a documented evidence-based disagreement between guidelines — flagged for clinical-co-lead review. Source-gap: SRC-STUPP-NEJM-2005, SRC-PERRY-NEJM-2017, SRC-CETEG-NOA09 not ingested.
Used By
No reverse references found in the YAML corpus.