OpenOnco · Treatment Plan

Treatment plan — Esophageal carcinoma

PLAN-VAR-ESOPHAGEAL-RELAPSED-V1 · v1 · 2026-05-13

Patient

VAR-ESOPHAGEAL-RELAPSED · Algorithm: ALGO-ESOPH-2L

DiagnosisEsophageal carcinoma

MOH / ICD-10C15

ICD-O-38070/3; C15

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-PDL1-CPS	(gene-level)	IA	SRC-NCCN-ESOPHAGEAL-2025 SRC-ESMO-ESOPHAGEAL-2024 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	PD-L1 CPS used as eligibility threshold for ICI in metastatic esophageal cancer. Esophageal SCC: CPS ≥10 — pembrolizumab + cisplatin + fluoropyrimidine 1L (KEYNOTE-590), and pembrolizumab monotherapy 2L (KEYNOTE-181 CPS≥10 subgroup). Esophageal adeno and GEJ: same CPS criteria as gastric adeno (NCCN 2025 treats GEJ adeno with gastric algorithm). Testing by IHC 22C3 pharmDx mandatory. Threshold-gated indication selection is performed by the algorithm layer (IND-ESOPH-METASTATIC-2L-PEMBRO-CPS10); this BMA entry surfaces ESCAT tier context only.	pembrolizumab + cisplatin + fluoropyrimidine (CPS≥10 SCC 1L per SRC-NCCN-ESOPHAGEAL-2025) pembrolizumab monotherapy (CPS≥10 SCC/adeno 2L per SRC-NCCN-ESOPHAGEAL-2025)	SRC-NCCN-ESOPHAGEAL-2025 SRC-ESMO-ESOPHAGEAL-2024

Primary current-line option

Standard plan

★ DEFAULT

Indication

IND-ESOPH-METASTATIC-2L-NIVO-SQUAMOUS

Regimen

Nivolumab monotherapy — 2L esophageal squamous (ATTRACTION-3)

Drugs + NSZU

Nivolumab (DRUG-NIVOLUMAB) 240 mg IV q2w (alternatively 480 mg IV q4w) · IV until progression / unacceptable toxicity / max 2 years · IV ⚠ NSZU — not for this indication

Hard contraindications

CI-PEMBROLIZUMAB-AUTOIMMUNE

Reason

Primary current-line option selected by ALGO-ESOPH-2L at step 2.

Other current-line alternatives (2 tracks)

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

Aggressive plan

Indication

IND-ESOPH-METASTATIC-2L-HER2-POSITIVE-T-DXD

Regimen

Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01)

Drugs + NSZU

Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 6.4 mg/kg · IV q3 weeks until progression / unacceptable toxicity · IV ⚠ NSZU — not for this indication

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-ESOPH-METASTATIC-2L-PEMBRO-CPS10

Regimen

Pembrolizumab monotherapy — 2L esophageal PD-L1 CPS ≥10 (KEYNOTE-181)

Drugs + NSZU

Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3w OR 400 mg IV q6w · IV until progression / unacceptable toxicity / max 35 cycles (~2 years) · IV ⚠ NSZU — not for this indication

Hard contraindications

CI-PEMBROLIZUMAB-AUTOIMMUNE

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-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-CT-CHEST-ABDOMEN-PELVIS	CT chest + abdomen + pelvis with IV contrast	Critical	imaging	—	all tracks
TEST-HER2-IHC-FISH	HER2 IHC + reflex FISH on tumor	Critical	—	CSD Lab ✓ (code TBC)	aggressive
TEST-ECHO	Echocardiography	Standard	imaging	—	aggressive

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). RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK
Frailty profile precluding CROSS / FLOT / definitive CRT in esophageal: ECOG ≥3, OR (age ≥75 + Charlson ≥3), OR composite (age ≥70 + albumin <3.0 + ≥10% weight loss + sarcopenia). Triggers definitive RT-only (palliative-intent), best-supportive-care with palliative stenting + nutrition optimization. RF-ESOPH-FRAILTY-AGE
Severe dysphagia with weight loss / aspiration risk in esophageal cancer: inability to swallow saliva, recurrent aspiration pneumonia, >10% weight loss in 3 months, OR malignant tracheoesophageal fistula. Mandates urgent palliative intervention (stenting OR dilation OR diversion) BEFORE any definitive systemic / RT therapy. RF-ESOPH-SEVERE-DYSPHAGIA-ASPIRATION
Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T). RF-FITNESS-ECOG-FIT

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Pembrolizumab (and other PD-1/PD-L1 inhibitors) augment T-cell responses; in patients with active autoimmunity or post-transplant immunosuppression, this can precipitate severe organ-specific flares (colitis, hepatitis, pneumonitis, transplant rejection) that may be fatal or require transplant loss. CI-PEMBROLIZUMAB-AUTOIMMUNE

What NOT to do

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

Standard plan (IND-ESOPH-METASTATIC-2L-NIVO-SQUAMOUS)

Do not prescribe in active autoimmune disease (lupus, IBD, untreated thyroiditis G3+) — irAE will progress uncontrollably.
Do not continue through Grade ≥3 irAE without permanent discontinuation consideration.
Do not ignore ICI-pneumonitis at the onset of dyspnea / cough — HRCT + corticosteroids.
Do not use at ECOG ≥3 — benefit of ICI in frail population not established; consider best-supportive-care.
Do not use after 1L ICI-exposure — no data on reuse; consider cytotoxic alternative.
Do not confirm the plan without verified funding pathway — NSZU 2026 does NOT cover nivolumab for esophagus.

Aggressive plan (IND-ESOPH-METASTATIC-2L-HER2-POSITIVE-T-DXD)

Do NOT use in squamous-cell esoph carcinoma (ESCC) — DG-01/04 and ToGA did not enroll ESCC, HER2 amplification rare.
Do NOT skip baseline + serial HRCT chest — ILD ~13.9% (DG-04), predominantly G1-2 but historically ~1% fatal.
Do NOT continue at suspicion of pneumonitis — immediate hold + pulmonologist + corticosteroids.
Do NOT prescribe without HER2 reconfirmation on fresh biopsy when feasible — HER2 loss after 1L common (~30%).
Do NOT prescribe at baseline LVEF <50% — cardiotoxicity of trastuzumab-based conjugates.
Do NOT skip prophylactic high-emetogenic antiemetics — T-DXd HEC.
Do NOT confirm the plan without verified funding pathway — NSZU 2026 does NOT cover T-DXd for gastric/esoph indications.

Aggressive plan (IND-ESOPH-METASTATIC-2L-PEMBRO-CPS10)

Do not prescribe without PD-L1 CPS testing — efficacy limited to CPS ≥10 subgroup.
Do not prescribe in active autoimmune disease — irAE will progress.
Do not continue through Grade ≥3 irAE without permanent discontinuation consideration.
Do not use at ECOG ≥3 — benefit of ICI in frail population not established.
Do not use after 1L ICI-exposure (KEYNOTE-590) — no data on reuse.
Do not confirm the plan without verified funding pathway — NSZU 2026 does NOT cover pembrolizumab for esophagus.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Nivolumab monotherapy — 2L esophageal squamous (ATTRACTION-3)

14-day cycles × Until progression / unacceptable toxicity / max 2 years

Aggressive plan

Induction · Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01)

21-day cycles × Until progression or unacceptable toxicity

Aggressive plan

Induction · Pembrolizumab monotherapy — 2L esophageal PD-L1 CPS ≥10 (KEYNOTE-181)

21-day cycles × Until progression / unacceptable toxicity / max 35 cycles

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-HER2-SOLID
What is the status of HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-ESOPH-METASTATIC-2L-HER2-POSITIVE-T-DXD. Expected value: HER2-positive (IHC 3+ OR IHC 2+/ISH-amplified) on archival or fresh biopsy. Reconfirmation on fresh biopsy preferred — HER2 loss after 1L trastuzumab occurs in ~30%..
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 HER2 status (solid tumors — gastric/GEJ/CRC scoring) (BIO-HER2-SOLID)? It is required by track(s): IND-ESOPH-METASTATIC-2L-HER2-POSITIVE-T-DXD. Expected value: HER2-positive (IHC 3+ OR IHC 2+/ISH-amplified) on archival or fresh biopsy. Reconfirmation on fresh biopsy preferred — HER2 loss after 1L trastuzumab occurs in ~30%..
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: 1/2 known (50%), 1 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-ESOPH-FRAILTY-AGE, RF-ESOPH-HIGH-RISK-BIOLOGY, RF-ESOPH-INFECTION-SCREENING, RF-ESOPH-SEVERE-DYSPHAGIA-ASPIRATION, RF-ESOPH-TRANSFORMATION-PROGRESSION, RF-ESOPHAGEAL-POST-CROSS-NON-PCR, RF-OLIGOMET-DEFINITION

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-HER2-SOLID`	HER2 status (solid tumors — gastric/GEJ/CRC scoring)	pathologist	no	IND-ESOPH-METASTATIC-2L-HER2-POSITIVE-T-DXD	Verify result, method, specimen, and report date before sign-off. Expected/constraint: HER2-positive (IHC 3+ OR IHC 2+/ISH-amplified) on archival or fresh biopsy. Reconfirmation on fresh biopsy preferred — HER2 loss after 1L trastuzumab occurs in ~30%.

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-DESTINY-GASTRIC01-SHITARA-2020: Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer (2020)
SRC-DESTINY-GASTRIC04-SHITARA-2025: Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer (2025)
SRC-ESMO-ESOPHAGEAL-2024: ESMO Esophageal Cancer (2024)
SRC-NCCN-ESOPHAGEAL-2025: NCCN Esophageal and EGJ 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: 2026-05-13.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT06787313	Precision Palliative Care for Patients With Advanced Esophageal Cancer	N/A	RECRUITING	Fudan University	—	Single country
NCT05473156	A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients with Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected Malignancies	PHASE1 / PHASE2	RECRUITING	AP Biosciences Inc.	—	Surrogate endpoint only Single country
NCT06790797	Investigating the Biomarkers in Tumor and Peripheral Blood to Evaluate the Efficacy of Cancer Immunotherapy in Chest Cancer Patients	N/A	RECRUITING	Zhao Jun	—	Single country
NCT07070466	Ivonescimab in Comb. With FOLFOX in Advanced HER2 Neg. GEA	PHASE2	RECRUITING	Massachusetts General Hospital	—	Small N (<50) Surrogate endpoint only Single country
NCT05875870	Effects of Bright-light Exposure Combined With Specific Exercise Training (BEST) Program in Patients With Cancer	NA	RECRUITING	Taipei Veterans General Hospital, Taiwan	—	Single country
NCT06535607	Study of Volrustomig as Monotherapy or in Combination With Anti- Cancer Agents in Participants With Advanced/Metastatic Solid Tumors	PHASE2	RECRUITING	AstraZeneca	—	Surrogate endpoint only
NCT03222895	Distribution of Lymph Node Metastases in Esophageal Carcinoma	N/A	RECRUITING	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	—	—
NCT06339619	Combination Immunotherapy of Adebrelimab With Apatinib and Tegafur for Immune Rechallenge Therapy in Esophageal Squamous Cell Carcinoma	PHASE2	RECRUITING	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	—	Small N (<50) Surrogate endpoint only Single country
NCT05775939	PET/CT Imaging to Evaluate Cardiac Radiation Damage in Patients With Lung or Esophageal Cancer, EUCLID Trial	NA	RECRUITING	Thomas Jefferson University	—	Small N (<50) Single country
NCT06077981	Comparison of 0.4% Hyaluronic Acid Solution Versus Hydroxyethylamide Solution in Submucosal Endoscopic Resections	NA	RECRUITING	Instituto do Cancer do Estado de São Paulo	—	Small N (<50) 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
Standard plan Nivolumab monotherapy — 2L esophageal squamous (ATTRACTION-3) (REG-NIVO-MONO-ESOPH-2L)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Trastuzumab deruxtecan (T-DXd) — 2L+ HER2+ gastric (DESTINY-Gastric01) (REG-TDXD-GASTRIC)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Pembrolizumab monotherapy — 2L esophageal PD-L1 CPS ≥10 (KEYNOTE-181) (REG-PEMBRO-MONO-ESOPH-2L)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT06787313 Precision Palliative Care for Patients With Advanced Esophageal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05473156 A Study to Investigate the Safety, Pharmacokinetics, and Clinical Activity of AP203 in Patients with Locally Advanced or Metastatic Solid Tumors, and Expansion to Selected Malignancies No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06790797 Investigating the Biomarkers in Tumor and Peripheral Blood to Evaluate the Efficacy of Cancer Immunotherapy in Chest Cancer Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07070466 Ivonescimab in Comb. With FOLFOX in Advanced HER2 Neg. GEA No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05875870 Effects of Bright-light Exposure Combined With Specific Exercise Training (BEST) Program in Patients With Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06535607 Study of Volrustomig as Monotherapy or in Combination With Anti- Cancer Agents in Participants With Advanced/Metastatic Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT03222895 Distribution of Lymph Node Metastases in Esophageal Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06339619 Combination Immunotherapy of Adebrelimab With Apatinib and Tegafur for Immune Rechallenge Therapy in Esophageal Squamous Cell Carcinoma No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05775939 PET/CT Imaging to Evaluate Cardiac Radiation Damage in Patients With Lung or Esophageal Cancer, EUCLID Trial No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06077981 Comparison of 0.4% Hyaluronic Acid Solution Versus Hydroxyethylamide Solution in Submucosal Endoscopic Resections 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: 2026-05-13.

plan_id: PLAN-VAR-ESOPHAGEAL-RELAPSED-V1 | version: 1 | generated: 2026-05-13T10:01:51.956395+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.