OpenOnco · Treatment Plan

Treatment plan — Low-grade glioma

PLAN-BMA-MAP2K1_LGG-V1 · v1 · 2026-08-17

Patient

BMA-MAP2K1_LGG · Algorithm: ALGO-GLIOMA-LGG-1L

DiagnosisLow-grade glioma

MOH / ICD-10C71

ICD-O-39400/3; C71

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
ESCAT: clinical review pendingBIO-MAP2K1	MAP2K1 activating mutation — low-grade glioma (LGG); BRAF-fusion-negative, IDH-wildtype or IDH-mutant; MAPK pathway alternative activation	IIA	Standard care 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

Primary current-line option

Aggressive plan

★ DEFAULT

Indication

IND-GLIOMA-LOW-GRADE-1L-RT-PCV

Regimen

Radiotherapy + PCV (procarbazine/lomustine/vincristine) — high-risk low-grade glioma

Drugs + NSZU

Procarbazine (DRUG-PROCARBAZINE) 60 mg/m² PO days 8-21 of each cycle · q6w (42-day cycles) × 6 cycles · PO ✗ Not registered in UA
Lomustine (DRUG-LOMUSTINE) 110 mg/m² PO day 1 of each cycle · q6w × 6 cycles · PO ✗ Not registered in UA
Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² IV (cap 2 mg) days 8 and 29 of each cycle · q6w × 6 cycles · IV ⚠ NSZU — not for this indication

Reason

Primary current-line option selected by ALGO-GLIOMA-LGG-1L at step 3.

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

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Radiotherapy + PCV (procarbazine/lomustine/vincristine) — high-risk low-grade glioma

42-day cycles × 6 cycles adjuvant (after RT 54 Gy/30 fx)

MDT brief

Discussion questions (2, 1 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
BLOCKING OQ-BIOMARKER-IDH-MUTATION
What is the status of IDH1 / IDH2 mutation status (BIO-IDH-MUTATION)? It is required by track(s): IND-GLIOMA-LOW-GRADE-1L-RT-PCV. Expected value: IDH1 R132H mutation (or non-canonical IDH1/IDH2) — defines IDH-mutant astrocytoma / oligodendroglioma.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist

MDT talk tree (3 steps)

#	Owner	Topic	Action
1	molecular_geneticist	Biomarker status BLOCKING	What is the status of IDH1 / IDH2 mutation status (BIO-IDH-MUTATION)? It is required by track(s): IND-GLIOMA-LOW-GRADE-1L-RT-PCV. Expected value: IDH1 R132H mutation (or non-canonical IDH1/IDH2) — defines IDH-mutant astrocytoma / oligodendroglioma.
2	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (2)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-IDH-MUTATION

Data quality

Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.

Biomarker coverage: 0/1 known (0%), 1 missing, 1 default-track gaps
Unevaluated RedFlags: RF-CMMRD-CONFIRMED-CARRIER, 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, RF-NF1-CONFIRMED-CARRIER, RF-NF1-FAMILY-HISTORY-SUSPICION, RF-NF2-SCHWANNOMATOSIS-CARRIER, RF-RHABDOID-PREDISPOSITION-CONFIRMED-CARRIER

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-IDH-MUTATION`	IDH1 / IDH2 mutation status	molecular_geneticist	yes	IND-GLIOMA-LOW-GRADE-1L-RT-PCV	Verify result, method, specimen, and report date before sign-off. Expected/constraint: IDH1 R132H mutation (or non-canonical IDH1/IDH2) — defines IDH-mutant astrocytoma / oligodendroglioma

Technical MDT skill metadata (2/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-EANO-GBM-2024: EANO Guidelines on Diagnosis and Treatment of Diffuse Gliomas of Adulthood (2024 update)
SRC-NCCN-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)

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: 2026-08-17.

NCT	Title	Phase	Status	Sponsor	UA	Signals	Eligibility (excerpt)
NCT04923126	SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma	PHASE1 / PHASE2	RECRUITING	St. Jude Children's Research Hospital	—	Surrogate endpoint only Single country

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).

Option	UA registration	NSZU	Cost orientation	Access pathway
Aggressive plan Radiotherapy + PCV (procarbazine/lomustine/vincristine) — high-risk low-grade glioma (REG-RT-PCV-LGG) 2/3 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not 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: 2026-08-17.

plan_id: PLAN-BMA-MAP2K1_LGG-V1 | version: 1 | generated: 2026-08-17T08:06:31.904238+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.