OpenOnco · Treatment Plan

Treatment plan — Colorectal carcinoma

PLAN-CRC-MET-MSI-H-1L-001-V1 · v1 · 2026-05-13

Patient

CRC-MET-MSI-H-1L-001 · Algorithm: ALGO-CRC-METASTATIC-1L

DiagnosisColorectal carcinoma

MOH / ICD-10C18-C20

ICD-O-38140/3; C18, C19, C20

StageIV

Histologyadenocarcinoma_mucinous

Clinical significance of mutations (ESCAT)

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

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-MSI-STATUS	MSI-H	IA	SRC-KEYNOTE-177-ANDRE-2020 SRC-NCCN-COLON-2025 SRC-ESMO-CRC-2024 Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap.	MSI-H (microsatellite instability-high) CRC is the primary biomarker for first-line pembrolizumab monotherapy (KEYNOTE-177; mPFS 16.5 vs 8.2 mo, HR 0.60; FDA-approved 2020 for 1L mCRC MSI-H). Pembrolizumab is also FDA-approved tumor-agnostically for MSI-H/dMMR solid tumors (KEYNOTE-158, 2017). MSS/pMMR CRC does not benefit from ICI monotherapy. MSI-H (~5% of metastatic CRC) is typically detected by PCR-based fragment analysis or NGS; result correlates closely with IHC-based dMMR testing (MLH1/MSH2/MSH6/PMS2 loss). Threshold selection (MSI-H positive/negative) enforced by algorithm layer; this BMA entry surfaces ESCAT tier context only. For Lynch syndrome germline implications see BMA entries for BIO-MLH1 / BIO-MSH2 / BIO-MSH6 / BIO-PMS2.	pembrolizumab monotherapy (MSI-H 1L mCRC per SRC-KEYNOTE-177-ANDRE-2020, SRC-NCCN-COLON-2025) pembrolizumab monotherapy (tumor-agnostic MSI-H per SRC-ESMO-CRC-2024)	SRC-KEYNOTE-177-ANDRE-2020 SRC-NCCN-COLON-2025 SRC-ESMO-CRC-2024

⚠️ Not included in plan

Biomarker	Status
BIO-MMR-STATUS	Not in KB — ask clinician to verify
BIO-BRAF-V600E	Excluded (negative)
KRAS	Not in KB — ask clinician to verify

Primary current-line option

Aggressive plan

★ DEFAULT

Indication

IND-CRC-METASTATIC-1L-MSI-H-PEMBRO

Regimen

Pembrolizumab monotherapy (MSI-H mCRC 1L)

Drugs + NSZU

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

Hard contraindications

CI-PEMBROLIZUMAB-AUTOIMMUNE

Reason

Primary current-line option selected by ALGO-CRC-METASTATIC-1L at step 1; branch-driving red flag: RF-CRC-MSI-H-ACTIONABILITY.

Other current-line alternatives (1 tracks)

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

Aggressive plan

Indication

IND-CRC-OLIGOMET-LIVER-LIMITED

Regimen

FOLFOX (mFOLFOX6)

Drugs + NSZU

Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV over 2h, day 1 · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV over 2h, day 1 (concurrent with oxaliplatin) · IV ✓ NSZU covered
5-Fluorouracil (DRUG-5-FLUOROURACIL) 400 mg/m² IV bolus + 2400 mg/m² CIV over 46h · Day 1 bolus, day 1-2 CIV · IV ✓ NSZU covered

Reason

Current-line alternative presented for HCP consideration

Why this branch was chosen

Triggers from the patient profile that fired and drove the chosen branch.

Step 1 → branch IND-CRC-METASTATIC-1L-MSI-H-PEMBRO

RF-CRC-MSI-H-ACTIONABILITY ★ winner: MSI-high / dMMR mCRC — treatment-defining biomarker. KEYNOTE-177 established pembrolizumab 1L over FOLFOX+bev (PFS 16.5 vs 8.2 mo). This RF intensifies toward the immunotherapy track and overrides the default RAS/BRAF-driven chemo algorithm. SRC-NCCN-COLON-2025SRC-ESMO-COLON-2024

Pre-treatment investigations

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

ID	Name	Priority	Category	Where to order	Needed for
TEST-CT-CHEST-ABDOMEN-PELVIS	CT chest + abdomen + pelvis with IV contrast	Critical	imaging	—	all tracks
TEST-DMMR-IHC	MMR proteins IHC (MLH1 / MSH2 / MSH6 / PMS2)	Critical	histology	CSD Lab ✓ (code TBC)	all tracks
TEST-MSI-PCR-OR-NGS	MSI status by PCR or NGS	Critical	histology	CSD Lab: M065 CSD Lab ✓ (code TBC)	all tracks
TEST-RAS-EXTENDED	RAS extended panel (KRAS exons 2-4 + NRAS exons 2-4)	Critical	histology	CSD Lab: M065	all tracks
TEST-CEA	CEA	Standard	lab	—	all tracks
TEST-MRI-BRAIN-CONTRAST	MRI brain with contrast	Standard	imaging	—	desired (aggressive)
TEST-PET-CT	FDG PET/CT (whole body)	Standard	imaging	—	desired (aggressive)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

MSI-high / dMMR mCRC — treatment-defining biomarker. KEYNOTE-177 established pembrolizumab 1L over FOLFOX+bev (PFS 16.5 vs 8.2 mo). This RF intensifies toward the immunotherapy track and overrides the default RAS/BRAF-driven chemo algorithm. RF-CRC-MSI-H-ACTIONABILITY
Liver-limited oligometastatic colorectal cancer (CRLM, colorectal liver metastases) — a distinct subset of stage IV CRC where intensified treatment with hepatic resection (or ablation) added to systemic chemo is potentially curative. Definition (per NCCN Colon v3.2025 + ESMO CRC 2024 + EORTC 40983 / Nordlinger 2008 trial framework): ≤5 liver metastatic lesions, all R0-resectable on multidisciplinary review, no extrahepatic disease, ECOG 0-1 fitness, controllable primary tumour. Triggers MDT (medical onc + hepatobiliary surgery + radiation onc + radiology) consideration of perioperative FOLFOX (or FOLFOXIRI in selected patients) + hepatic metastasectomy. Distinct from gastroesophageal OMEC-1 oligomet (RF-OLIGOMET-DEFINITION) — CRC oligomet uses ≤5 liver lesions (not ≤3 distant), restricts to liver only (extrahepatic excluded), and HER2-positive does NOT disqualify (anti-HER2 second-line track separate from periop intensification decision). RF-CRC-OLIGOMET-LIVER-DEFINITION

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

Aggressive plan (IND-CRC-METASTATIC-1L-MSI-H-PEMBRO)

Do NOT start FOLFOX/FOLFIRI ± bev/cetux in MSI-H mCRC 1L — substantial PFS loss vs ICI
Do NOT continue pembrolizumab through Grade 3+ immune-related AE without specialist consultation
Do NOT start pembrolizumab without prior MSI/dMMR confirmation by validated assay

Aggressive plan (IND-CRC-OLIGOMET-LIVER-LIMITED)

Do NOT proceed without MDT review (medical onc + hepatobiliary surgery + radiation onc + radiology) — resectability assessment is the gate
Do NOT offer hepatic metastasectomy without ≤5 R0-resectable liver-limited lesions + adequate future liver remnant on imaging review
Do NOT include extrahepatic disease (lung, peritoneal, distant LN, brain) — these are explicit exclusions and route to standard 1L metastatic CRC management
Do NOT continue bevacizumab perioperatively — hold ≥6 weeks before hepatectomy due to wound-healing / hepatic-regeneration risk; resume post-recovery if indicated
Do NOT initiate during ongoing GI bleed / obstruction / perforation — emergency management first (RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION)
Do NOT default to non-MDT single-surgeon decision — refer to a hepatobiliary surgeon at an appropriate-volume centre

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Pembrolizumab monotherapy (MSI-H mCRC 1L)

21-day cycles × Until progression / unacceptable toxicity / max 35 cycles per KEYNOTE-177

Aggressive plan

Induction · FOLFOX (mFOLFOX6)

14-day cycles × 12 cycles (6 mo) for adjuvant stage III; until progression / unacceptable toxicity for metastatic; 4 cycles (8 wk) periop trials

MDT brief

Discussion questions (1, 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

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	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
3	molecular_geneticist	Specialist review	Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.

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.

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: 1/1 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION, RF-CRC-FRAILTY-AGE, RF-CRC-HER2-AMP-ACTIONABLE, RF-CRC-INFECTION-SCREENING, RF-CRC-OLIGOMET-LIVER-DEFINITION, RF-CRC-RAS-MUTANT, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION

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-ESMO-COLON-2024: ESMO CRC Clinical Practice Guideline (2024)
SRC-ESMO-CRC-2024: ESMO colorectal cancer guideline (2024) (TODO: confirm citation) ()
SRC-KEYNOTE-177-ANDRE-2020: Pembrolizumab versus Chemotherapy for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer (2020)
SRC-NCCN-COLON-2025: NCCN Colon / Rectal Cancer (v.4.2025)

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
NCT06819280	Autologous Tumor-Infiltrating Lymphocyte (GT307) for Treatment of Patients With Advanced Colorectal Cancer	NA	RECRUITING	Grit Biotechnology	—	Small N (<50) Surrogate endpoint only Single country
NCT06794086	SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases	PHASE3	RECRUITING	Jun Huang	—	Small N (<50) Surrogate endpoint only Single country
NCT05288205	Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation	PHASE1 / PHASE2	RECRUITING	Allist Pharmaceuticals, Inc.	—	Single country
NCT06848842	Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Liver Metastases	PHASE2	RECRUITING	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	—	Small N (<50) Surrogate endpoint only Single country
NCT07090291	China Colorectal Cancer Screening Trial 1 (C-Cost1)	NA	RECRUITING	Zhejiang University	—	Single country
NCT06167967	Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer	NA	RECRUITING	Sir Run Run Shaw Hospital	—	Single country
NCT06282445	Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer	PHASE2	RECRUITING	The Fourth Affiliated Hospital of Zhejiang University School of Medicine	—	Small N (<50) Surrogate endpoint only Single country
NCT04693377	Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial	NA	RECRUITING	M.D. Anderson Cancer Center	—	Small N (<50) Single country
NCT07333053	Clinical Efficacy of Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer	NA	RECRUITING	Quanda Liu	—	Small N (<50) Surrogate endpoint only Single country
NCT07529301	Functional and Respiratory Predictors of Early Postoperative Outcomes	N/A	RECRUITING	Müşerref Ebru YALÇIN	—	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
Aggressive plan Pembrolizumab monotherapy (MSI-H mCRC 1L) (REG-PEMBROLIZUMAB-MSI-MONO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan FOLFOX (mFOLFOX6) (REG-FOLFOX)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT06819280 Autologous Tumor-Infiltrating Lymphocyte (GT307) for Treatment of Patients With Advanced Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06794086 SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05288205 Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06848842 Ivonescimab Plus Chemotherapy in Patients With Initially Unresectable Colorectal Cancer Liver Metastases No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07090291 China Colorectal Cancer Screening Trial 1 (C-Cost1) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06167967 Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06282445 Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04693377 Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07333053 Clinical Efficacy of Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07529301 Functional and Respiratory Predictors of Early Postoperative Outcomes 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-CRC-MET-MSI-H-1L-001-V1 | version: 1 | generated: 2026-05-13T10:01:52.941119+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.