Glioblastoma with adverse molecular biology under WHO CNS5 classification: MGMT promoter...
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| ID | RF-GBM-HIGH-RISK-BIOLOGY |
|---|---|
| Tipo | Sinal de alerta |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff |
| Doenças | DIS-GBM |
| Fontes | SRC-EANO-GBM-2024 SRC-NCCN-CNS-2025 |
Origem da bandeira vermelha
| Definição | 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. |
|---|---|
| Direcção clínica | intensificar |
| Categoria | high-risk-biology |
Lógica de Desencadeamento
{
"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"
}
Notas
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.
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