OpenOnco · Treatment Plan

Treatment plan — Endometrial carcinoma

PLAN-BMA-CTNNB1_ENDOMETRIAL-V1 · v1 · 2026-08-17

Patient

BMA-CTNNB1_ENDOMETRIAL · Algorithm: ALGO-ENDOMETRIAL-ADVANCED-1L

DiagnosisEndometrial carcinoma

MOH / ICD-10C54

ICD-O-38380/3; C54.1

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-CTNNB1	CTNNB1 exon 3 activating mutation (S33C, S37F, T41A, S45P) in endometrial carcinoma; NSMP molecular class; associated with L1CAM overexpression and high recurrence risk despite low stage	IIB	Standard care SRC-ESGO-ENDOMETRIAL-2025: Level B (Supports, Poor Outcome) SRC-NCCN-UTERINE-2025: Level Category 2A (Supports, Poor Outcome)	CTNNB1 exon 3 mutations occur in ~25–30% of endometrial carcinoma (EC), predominantly endometrioid histology within the NSMP (No Specific Molecular Profile) molecular class per TCGA/ESGO/ESMO classification. CTNNB1 mutation is a key risk-stratifier within NSMP/intermediate-risk EC: presence of CTNNB1 exon 3 mutation is associated with L1CAM (L1 cell adhesion molecule) overexpression, which is an independent predictor of lymphovascular invasion and distant metastasis even in FIGO stage I-II disease. PORTEC-3 subset analyses and ESGO/ESMO/ESTRO 2023 EC risk stratification: CTNNB1-mutant FIGO IA-IB endometrioid EC is reclassified to "high-intermediate risk" or "high risk" — warranting consideration of adjuvant chemotherapy (carboplatin/paclitaxel) rather than vaginal brachytherapy alone, which would be standard for low-risk NSMP. No CTNNB1-targeted therapy approved for EC. WNT pathway inhibitors (porcupine inhibitors such as WNT-974, OMP-54F28; tankyrase inhibitors) are in early-phase trials but not endometrial-specific. Nirogacestat (gamma-secretase inhibitor, FDA 2023 for desmoid tumor) targets Notch pathway with WNT pathway intersection but is not approved for EC.	carboplatin AUC 5 + paclitaxel 175 mg/m² q3w × 6 cycles — adjuvant chemotherapy for CTNNB1-mutant FIGO IA-IB endometrioid EC reclassified to high-intermediate/high risk per ESGO/ESMO/ESTRO 2023 guidelines vaginal brachytherapy (VBT) ± external beam RT — per risk stratification; CTNNB1 mutation upgrades VBT-only recommendation to CT consideration	SRC-NCCN-UTERINE-2025 SRC-ESGO-ENDOMETRIAL-2025 SRC-ESMO-ENDOMETRIAL-2022

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-ENDOMETRIAL-ADVANCED-1L-PEMBRO-CHEMO

Regimen

Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w · Continuous up to 2 years · IV ⚠ NSZU — not for this indication
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication

Reason

Primary current-line option selected by ALGO-ENDOMETRIAL-ADVANCED-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Aggressive plan

Indication

IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO

Regimen

Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)

Drugs + NSZU

Dostarlimab (DRUG-DOSTARLIMAB) 500 mg IV q3w → 1000 mg q6w maintenance · With chemo cycles 1-6 + maintenance up to 3 years · IV ✗ Not registered in UA
Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication
Paclitaxel (DRUG-PACLITAXEL) 175 mg/m² IV · Day 1 x 6 cycles · IV ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Pre-treatment investigations

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

ID	Name	Priority	Category	Where to order	Needed for
TEST-CECT-CAP	CECT chest/abdomen/pelvis	Critical	imaging	—	all tracks
TEST-ER-PR-IHC	ER + PR immunohistochemistry on tumor	Critical	—	CSD Lab ✓ (code TBC)	all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

Patient with active or incompletely controlled pre-existing autoimmune or inflammatory disease (sarcoidosis, rheumatoid arthritis, IBD, SLE, autoimmune hepatitis, inflammatory myopathy, myasthenia gravis, or similar) is considered for immune checkpoint inhibitor (ICI) therapy — elevated risk of immune-related adverse events (irAE) flare or de-novo grade 3-4 irAE. Requires specialist (rheumatology / pulmonology / gastroenterology) pre-treatment review; prefer lower-irAE-burden backbone when options exist (pembrolizumab mono > ipilimumab+nivolumab).
Pre-existing autoimmune disease is present in ~10-15% of patients eligible for ICI therapy; historically excluded from pivotal trials. Real-world data (Abdel-Wahab 2018, 3557 pts) shows 55% experienced irAE flare and ~29% required…
RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISKSRC-SITC-ICI-IRAEMANAGEMENT-2021SRC-ESMO-ICI-TOXICITY-2022

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L)

21-day cycles × Chemo x 6; pembro maintenance up to 2 years

Aggressive plan

Induction · Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR)

21-day cycles × Chemo x 6; dostarlimab maintenance up to 3 years

MDT brief

Discussion questions (2, 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
OQ-BIOMARKER-DMMR-IHC
What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
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.
→ pathologist

MDT talk tree (3 steps)

#	Owner	Topic	Action
1	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
2	pathologist	Biomarker status	What is the status of Mismatch repair protein expression by IHC (BIO-DMMR-IHC)? It is required by track(s): IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO. Expected value: deficient.
3	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.

Biomarker coverage: 0/1 known (0%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-ENDOMETRIAL-FIT-FOR-LENVATINIB-COMBO, RF-ENDOMETRIAL-FRAILTY-AGE, RF-ENDOMETRIAL-HIGH-RISK-BIOLOGY, RF-ENDOMETRIAL-INFECTION-SCREENING, RF-ENDOMETRIAL-ORGAN-DYSFUNCTION, RF-ENDOMETRIAL-TRANSFORMATION-PROGRESSION, RF-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-TAMOXIFEN-ENDOMETRIAL-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM, RF-REPRODUCTIVE-PCOS-ENDOMETRIAL-PREVENTION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-DMMR-IHC`	Mismatch repair protein expression by IHC	pathologist	no	IND-ENDOMETRIAL-ADVANCED-1L-DOSTARLIMAB-CHEMO	Verify result, method, specimen, and report date before sign-off. Expected/constraint: deficient

Technical MDT skill metadata (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-ENDOMETRIAL-2022: ESMO-ESGO-ESTRO Endometrial Consensus (2022)
SRC-GY018-MAKKER-2022: Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer ()
SRC-NCCN-UTERINE-2025: NCCN Uterine Neoplasms (2025.v2)
SRC-RUBY: Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer (2023)

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)
NCT05919264	FOG-001 in Locally Advanced or Metastatic Solid Tumors	PHASE1 / PHASE2	RECRUITING	Parabilis Medicines, Inc.	—	Surrogate endpoint only

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 Pembrolizumab + carbo + paclitaxel (endometrial advanced 1L) (REG-PEMBRO-CARBO-PACLI-ENDOM)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Dostarlimab + carbo + paclitaxel (endometrial advanced 1L dMMR) (REG-DOSTARLIMAB-CARBO-PACLI-ENDOM) 1/3 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT05919264 FOG-001 in Locally Advanced or Metastatic 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: 2026-08-17.

plan_id: PLAN-BMA-CTNNB1_ENDOMETRIAL-V1 | version: 1 | generated: 2026-08-17T08:06:31.637174+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.