Glioblastoma with adverse molecular biology under WHO CNS5 classification: MGMT promoter...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-GBM-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-GBM`
Sources	`SRC-EANO-GBM-2024` `SRC-NCCN-CNS-2025`

Red Flag Origin

Definition	Glioblastoma with adverse molecular biology under WHO CNS5 classification: MGMT promoter unmethylated (poor TMZ response — Stupp benefit attenuated), IDH-wildtype (defines true glioblastoma per WHO 2021 — IDH-mutant astrocytomas reclassified), CDKN2A/B homozygous deletion (independent poor-prognostic marker), or TERT promoter mutation. Drives MDT discussion of clinical-trial enrollment and intensified follow-up.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "mgmt_methylation_status",
      "value": "unmethylated"
    },
    {
      "finding": "idh_status",
      "value": "wildtype"
    },
    {
      "finding": "cdkn2a_b_homozygous_deletion",
      "value": true
    },
    {
      "finding": "tert_promoter_mutation",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

MGMT-unmethylated GBM: TMZ benefit substantially smaller (median OS 12-15 mo vs 21-23 mo for methylated per Stupp / EORTC 26981); strong rationale for clinical-trial enrollment (CeTeG / NOA-09 lomustine + TMZ for elderly methylated; tumor-treating fields TTF per EF-14 add 4-5 mo OS; bevacizumab does not extend OS but benefits steroid-sparing and symptomatic care). IDH-wildtype is now the defining molecular feature of GBM per WHO CNS5 (2021) — IDH-mutant astrocytomas grade 4 are a separate entity with substantially better prognosis and different algorithms (vorasidenib emerging). CDKN2A/B deletion in IDH-mut grade 3-4 astrocytoma upgrades behavior to grade 4-equivalent.

Used By

No reverse references found in the YAML corpus.