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OpenOnco · DIS-GLIOMA-LOW-GRADE · BIO-MAP2K1 (ESCAT IIA)
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OpenOnco · Treatment Plan
Treatment plan — DIS-GLIOMA-LOW-GRADE
PLAN-BMA-MAP2K1_LGG-V1 · v1 · 2026-05-04
Patient
BMA-MAP2K1_LGG · Algorithm: ALGO-GLIOMA-LGG-1L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-MAP2K1MAP2K1 activating mutation — low-grade glioma (LGG); BRAF-fusion-negative, IDH-wildtype or IDH-mutant; MAPK pathway alternative activationIIA
  • SRC-NCCN-CNS-2025: Level Category 2A (Supports, Sensitivity/Response)
  • SRC-EANO-LGG-2024: Level B (Supports, Sensitivity/Response)
MAPK pathway activation is the hallmark of pediatric-type low-grade glioma (pLGG) and occurs in ~90% via BRAF-KIAA1549 fusion (~70%), BRAF V600E (~15%), or alternative MAPK alterations including MAP2K1 mutations (~5–10% of BRAF-fusion-negative pLGG). The FIREFLY-1 phase II trial (Kilburn et al., JCO 2024) demonstrated tovorafenib (type II RAF inhibitor) activity in pLGG with MAPK pathway alterations including MAP2K1 mutations: ORR 67% overall; MAP2K1 cohort showed responses. Trametinib (MEK1/2 inhibitor) has demonstrated activity in MAPK-pathway-altered pLGG in the TRAM-01 and FIREFLY-2 trials. In adult LGG, MAP2K1 mutations occur in ~5% (predominantly IDH-wildtype histiocytic NEC); data more limited. For adult IDH-mutant LGG, vorasidenib (IDH1/2 inhibitor) is now standard (INDIGO trial; FDA 2024) — see BMA-IDH-MUTATION-GLIOMA-LOW-GRADE. MAP2K1 mutations in adult LGG without IDH: MEK inhibitors investigational. NCCN CNS 2025: trametinib / tovorafenib Category 2A for MAPK-altered pLGG.trametinib 0.025 mg/kg PO QD (pediatric dosing; adult 2 mg/day) — MAP2K1-mutant LGG investigational (TRAM-01 regimen)
tovorafenib 420 mg/m² PO QW — BRAF-altered or MAPK-pathway-altered pLGG (FIREFLY-1 eligible)
clinical trial enrollment preferred for MAP2K1-mutant LGG (adult or pediatric)
  • SRC-NCCN-CNS-2025
  • SRC-EANO-LGG-2024

Treatment options (1 tracks)

Aggressive plan
★ DEFAULT
Indication
IND-GLIOMA-LOW-GRADE-1L-RT-PCV
Regimen
—
Reason
Engine default per algorithm ALGO-GLIOMA-LGG-1L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-GLIOMA-LOW-GRADE-1L-RT-PCV'}, 'fired_red_flags': [], 'winner_red_flag': None}

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-GLIOMA-LOW-GRADE-1L-RT-PCV)
  • Do not skip molecular profiling (IDH1/2, 1p/19q, ATRX, MGMT, CDKN2A) — defines grade per WHO 5th ed. and choice of adjuvant
  • Do not prescribe RT+PCV to patients with IDH-wildtype LGG — reclassify to GBM, requires Stupp protocol
  • Do not start PCV without baseline LFTs, CBC + contraception (procarbazine teratogen + EtOH-disulfiram-like reaction)
  • Do not skip levetiracetam-based AED in patients with seizures — does not induce P450, unlike phenytoin/carbamazepine

MDT brief

Skills (recommended) — for consideration (1)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
    skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

  • OQ-LDH-CURRENT
    What is the current LDH? Marker of tumor burden and transformation.
    LDH is part of the prognostic indices of indolent lymphomas.
    → hematologist

Data quality

  • Unevaluated RedFlags: RF-GLIOMA-LOW-GRADE-FRAILTY-AGE, RF-GLIOMA-LOW-GRADE-HIGH-RISK-BIOLOGY, RF-GLIOMA-LOW-GRADE-INFECTION-SCREENING, RF-GLIOMA-LOW-GRADE-INTRACRANIAL-PRESSURE, RF-GLIOMA-LOW-GRADE-ORGAN-DYSFUNCTION, RF-GLIOMA-LOW-GRADE-TRANSFORMATION-PROGRESSION

Skill catalog (1/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.
NCTTitlePhaseStatusSponsorUAEligibility (excerpt)
NCT04923126SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade GliomaPHASE1 / PHASE2RECRUITINGSt. Jude Children's Research Hospital—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
OptionUA registrationNSZUCost orientationAccess pathway
Aggressive plan
—
No regimen components on this track — availability unknown
— unknown— unknown₴-? — verify pathwaynot recorded
Trial · NCT04923126
SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-MAP2K1_LGG-V1 | version: 1 | generated: 2026-05-04T14:13:16.635448+00:00
Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.
Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.
This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.