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
BIO-SMARCB1	SMARCB1/INI1 biallelic loss-of-function — confirmed by loss of INI1 nuclear expression on IHC (BAF47/INI1 antibody); NGS/FISH for deletion confirmation optional	IA	SRC-EZH202-GOUNDER-2020: Level B (Supports, Sensitivity/Response) SRC-NCCN-SARCOMA: Level Category 2A (Supports, Sensitivity/Response) SRC-ESMO-SARCOMA-2024: Level B (Supports, Sensitivity/Response)	Tazemetostat (EPZ-6438), an EZH2 methyltransferase inhibitor, is FDA-approved (January 2020) for adults and pediatric patients (≥16 years) with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. This was the first FDA approval in this disease and the first EZH2-targeted approval in solid tumors. EZH-202 phase II (Gounder et al., Lancet Oncology 2020): N=62 evaluable; primary endpoint ORR by RECIST 1.1. ORR: 15% (9/62; 1 CR, 8 PR); clinical benefit rate (CR+PR+SD ≥32 weeks): 26%. mDOR in responders: not reached at time of analysis. Disease control rate: ~26% with durable SD. Safety profile: generally well-tolerated; rare secondary T-cell lymphoma risk (class-wide EZH2 inhibitor concern); myeloid malignancy risk with long-term use (monitoring recommended). INI1 loss (IHC) is the companion diagnostic — required for diagnosis and eligibility. Standard chemotherapy (doxorubicin-based) remains an option for fit patients with rapidly progressive disease; tazemetostat preferred for slow-growing/indolent course.	tazemetostat 800 mg PO BID continuously (no food restriction; 28-day cycles; continue until disease progression or unacceptable toxicity)	SRC-EZH202-GOUNDER-2020 SRC-NCCN-SARCOMA SRC-ESMO-SARCOMA-2024

Treatment options (1 tracks)

Standard plan

★ DEFAULT

Indication

IND-EPITHELIOID-SARCOMA-1L-TAZEMETOSTAT

Regimen

Tazemetostat monotherapy (advanced epithelioid sarcoma, SMARCB1/INI1-deficient)

Drugs + NSZU

Tazemetostat (DRUG-TAZEMETOSTAT) 800 mg PO twice daily (1600 mg/day total) · Continuous until progression or unacceptable toxicity · PO ✗ Not registered in UA

Reason

Engine default per algorithm ALGO-EPITHELIOID-SARCOMA-1L: {'step': 1, 'outcome': False, 'branch': {'result': 'IND-EPITHELIOID-SARCOMA-1L-TAZEMETOSTAT'}, 'fired_red_flags': [], 'winner_red_flag': None}

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-EPITHELIOID-SARCOMA-1L-TAZEMETOSTAT)

Do NOT prescribe without confirmed SMARCB1/INI1 loss by IHC — mandatory eligibility criterion
Do NOT combine with strong CYP3A4 inhibitors without dose reduction (reduce to 400 mg BID)
Do NOT ignore secondary malignancy risk — T-LBL/AML reported in pediatric sarcoma trials
Do NOT prescribe in pregnancy — embryo-fetal toxicity

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Tazemetostat monotherapy (adva

28-day cycles × Continuous until progression

MDT brief

Skills (recommended) — for consideration (1)

Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
skill: molecular_geneticistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Skill catalog (1/16 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-ESMO-SARCOMA-2024: ESMO soft-tissue sarcoma guideline (2024) (TODO: confirm citation) ()
SRC-EZH202-GOUNDER-2020: EZH-202: Tazemetostat in Epithelioid Sarcoma (Gounder et al., Lancet Oncology 2020) ()

Experimental options (clinical trials)

Last synced: 2026-05-04 · ctgov.

No active trials matched this scenario in ctgov.

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
Standard plan Tazemetostat monotherapy (advanced epithelioid sarcoma, SMARCB1/INI1-deficient) (REG-TAZEMETOSTAT-EPITHELIOID-SARCOMA) 1/1 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded

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

plan_id: PLAN-BMA-SMARCB1_EPITHELIOID_SARCOMA-V1 | version: 1 | generated: 2026-05-04T14:13:16.654143+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.