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-IDH-MUTATION	IDH1 R132 hotspot (R132C ~70%, R132L, R132G, R132H, R132S; ~13-20% of intrahepatic cholangiocarcinoma)	IA	SRC-CIVIC: Level A (Supports, Sensitivity/Response) SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level B (Supports, Better Outcome) SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	IDH1 R132 hotspot mutations occur in ~13-20% of intrahepatic cholangiocarcinoma and are FDA Level-1 actionable. Ivosidenib was FDA-approved 2021 for previously-treated IDH1-mutated locally advanced/metastatic cholangiocarcinoma based on ClarIDHy (Abou-Alfa Lancet Oncol 2020 — mPFS 2.7 vs 1.4 mo, HR 0.37; OS benefit on rank-preserving structural failure time analysis adjusted for crossover) per SRC-NCCN-HEPATOBILIARY. Comprehensive molecular profiling at diagnosis is recommended to identify IDH1-R132 patients who can be sequenced to ivosidenib in 2L after gemcitabine/cisplatin ± durvalumab (TOPAZ-1) 1L.	ivosidenib monotherapy (2L+ IDH1 R132-mutated cholangio per SRC-NCCN-HEPATOBILIARY)	SRC-NCCN-HEPATOBILIARY

Treatment options (1 tracks)

Standard plan

★ DEFAULT

Indication

IND-CHOLANGIO-ADVANCED-GEM-CIS

Regimen

Gemcitabine + cisplatin (advanced biliary tract cancer, 1L — ABC-02)

Drugs + NSZU

Gemcitabine (DRUG-GEMCITABINE) Gemcitabine 1000 mg/m² · Per regimen schedule · IV ⚠ NSZU — not for this indication
Cisplatin (DRUG-CISPLATIN) cisplatin 25 mg/m² IV d1, d8 q3w × 8 cycles · Per regimen schedule · IV ⚠ NSZU — not for this indication

Reason

Engine default per algorithm ALGO-CHOLANGIO-1L: {'step': None, 'note': 'decision tree fell through; using default_indication', 'result': 'IND-CHOLANGIO-ADVANCED-GEM-CIS', 'fired_red_flags': []}

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Gemcitabine + cisplatin (advan

21-day cycles × 6 cycles or until progression / toxicity

MDT brief

Data quality

Unevaluated RedFlags: RF-CHOLANGIO-FGFR2-FUSION-ACTIONABLE, RF-CHOLANGIOCARCINOMA-FRAILTY-AGE, RF-CHOLANGIOCARCINOMA-HIGH-RISK-BIOLOGY, RF-CHOLANGIOCARCINOMA-INFECTION-SCREENING, RF-CHOLANGIOCARCINOMA-ORGAN-DYSFUNCTION, RF-CHOLANGIOCARCINOMA-TRANSFORMATION-PROGRESSION

Skill catalog (0/16 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-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: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA	Eligibility (excerpt)
NCT03991832	Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors	PHASE2	RECRUITING	University Health Network, Toronto	—

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
Standard plan Gemcitabine + cisplatin (advanced biliary tract cancer, 1L — ABC-02) (REG-GEMCITABINE-CISPLATIN-CHOLANGIO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT03991832 Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors 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-IDH1_R132_CHOLANGIO-V1 | version: 1 | generated: 2026-05-04T14:13:16.597201+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.