OpenOnco · Treatment Plan

Treatment plan — Colorectal carcinoma

PLAN-CRC-MET-RAS-MUT-1L-001-V1 · v1 · 2026-05-12

Patient

CRC-MET-RAS-MUT-1L-001 · Algorithm: ALGO-CRC-METASTATIC-1L

DiagnosisColorectal carcinoma

MOH / ICD-10C18-C20

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

StageIV

Histologyadenocarcinoma

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-RAS-MUTATION	KRAS A146T	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS A146T — rare, anti-EGFR contraindication marker. No targeted therapy.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS exon 3 codon 59/61	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS exon 3 codon 59/61 in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS exon 4 codon 117/146	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS exon 4 codon 117/146 in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS G12D	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Better Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12D in mCRC predicts anti-EGFR resistance. No approved targeted therapy 2026; trial-only (MRTX1133, RMC-9805 + cetuximab combos).	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G12V	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12V in mCRC — anti-EGFR contraindication marker, no targeted therapy. Standard chemo ± anti-VEGF.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G12 (any)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G12 (any) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS G13D	IV	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G13D in mCRC — historical signal of partial cetuximab response (De Roock 2010) was not confirmed prospectively. Treat as RAS-mut, anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	KRAS G13 (any non-G13C)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS G13 (any non-G13C) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	KRAS Q61 (any)	IA	Molecular evidence option SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response) SRC-CIVIC: Level E (Supports, Sensitivity/Response)	KRAS Q61 (any) in mCRC — extended-RAS WT criterion fails; anti-EGFR (cetuximab/panitumumab) contraindicated. Standard chemo ± bevacizumab.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024
BIO-RAS-MUTATION	NRAS G12	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS codon 12 mutation in mCRC — extended RAS WT criterion fails; anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS G13	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS codon 13 in mCRC — anti-EGFR contraindicated.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS Q61K	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS Q61K in mCRC — anti-EGFR contraindication.	—	SRC-NCCN-COLON-2025
BIO-RAS-MUTATION	NRAS Q61R	IB	Molecular evidence option SRC-CIVIC: Level B (Supports, N/A) Resistance or avoidance signal SRC-CIVIC: Level A ⚠ Resistance SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level C ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	NRAS Q61R in mCRC — anti-EGFR (cetuximab/panitumumab) contraindication. Standard chemo ± bev; no NRAS-selective drug.	—	SRC-NCCN-COLON-2025 SRC-ESMO-COLON-2024

⚠️ Not included in plan

Biomarker	Status
BIO-MSI-STATUS	BIO definition in KB; no ESCAT BMA entry — verify with clinician
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-FOLFOX-BEV

Regimen

FOLFOX + Bevacizumab

Drugs + NSZU

Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · 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
Bevacizumab (DRUG-BEVACIZUMAB) 5 mg/kg · IV day 1 · IV ✓ NSZU covered

Reason

Primary current-line option selected by ALGO-CRC-METASTATIC-1L at step 6.

Other current-line alternatives (4 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

Aggressive plan

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

Current-line alternative presented for HCP consideration

Standard plan

Indication

IND-CRC-METASTATIC-1L-RAS-WT-LEFT

Regimen

FOLFOX + Cetuximab

Drugs + NSZU

Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV day 1 · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 400 mg/m² · IV day 1 · 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
Cetuximab (DRUG-CETUXIMAB) 500 mg/m² q2w (preferred for FOLFOX schedule; alternatively 400 mg/m² loading then 250 mg/m² weekly) · IV day 1 of each 14-d cycle · IV ✓ NSZU covered

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-CRC-METASTATIC-1L-FOLFOXIRI-BEV

Regimen

FOLFOXIRI + Bevacizumab

Drugs + NSZU

Irinotecan (DRUG-IRINOTECAN) 165 mg/m² · IV over 1h, day 1 · IV ✓ NSZU covered
Oxaliplatin (DRUG-OXALIPLATIN) 85 mg/m² · IV over 2h, day 1 · IV ✓ NSZU covered
Leucovorin (DRUG-LEUCOVORIN) 200 mg/m² · IV over 2h, day 1 · IV ✓ NSZU covered
5-Fluorouracil (DRUG-5-FLUOROURACIL) 3200 mg/m² CIV over 48h · Day 1-2 (no bolus) · IV ✓ NSZU covered
Bevacizumab (DRUG-BEVACIZUMAB) 5 mg/kg · IV day 1, before chemotherapy · IV ✓ NSZU covered

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-CT-CHEST-ABDOMEN-PELVIS	CT chest + abdomen + pelvis with IV contrast	Critical	imaging	—	aggressive
TEST-DMMR-IHC	MMR proteins IHC (MLH1 / MSH2 / MSH6 / PMS2)	Critical	histology	CSD Lab ✓ (code TBC)	aggressive
TEST-MSI-PCR-OR-NGS	MSI status by PCR or NGS	Critical	histology	CSD Lab: M065 CSD Lab ✓ (code TBC)	aggressive
TEST-RAS-EXTENDED	RAS extended panel (KRAS exons 2-4 + NRAS exons 2-4)	Critical	histology	CSD Lab: M065	aggressive
TEST-CEA	CEA	Standard	lab	—	aggressive
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

BRAF V600E mutation in mCRC: ~8-10% prevalence, poor prognosis (median OS halved vs BRAF-WT on standard chemo). Cetuximab/panitumumab ineffective. Encorafenib + cetuximab (BEACON CRC) is preferred 2L+; some 1L data favor FOLFOXIRI + bev intensification in MSS BRAF-mutant. RF-CRC-BRAF-V600E-POOR-PROGNOSIS
Frailty/age profile precluding doublet-intensive or triplet chemo: ECOG ≥3, OR (age ≥80 + Charlson ≥3), OR composite (age ≥75 + albumin <3.0 + ≥2 comorbidities). Triggers de-escalation toward 5-FU/LV mono, capecitabine mono, or best supportive care. RF-CRC-FRAILTY-AGE
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-FOLFOX-BEV)

Do NOT initiate within 28 days of major surgery (perforation / dehiscence risk)
Do NOT continue bevacizumab through uncontrolled HTN >160/100
Do NOT use in patients with high-risk varices / active hemoptysis

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

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

Standard plan (IND-CRC-METASTATIC-1L-RAS-WT-LEFT)

Do NOT use cetuximab/panitumumab in RAS-mutant CRC — bypassed signaling, no benefit
Do NOT use cetuximab in BRAF V600E mutant — confirmed no benefit (BEACON CRC)
Do NOT use cetuximab in right-sided RAS-WT — bevacizumab preferred per CALGB-80405
Do NOT skip rash prophylaxis — strongly correlates with response and impacts QoL

Aggressive plan (IND-CRC-METASTATIC-1L-FOLFOXIRI-BEV)

Do NOT use in ECOG PS ≥ 2 — toxicity unacceptable; use doublet (FOLFOX+bev or FOLFIRI+bev)
Do NOT use in MSI-H/dMMR patients — pembrolizumab 1L is preferred (KEYNOTE-177)
Do NOT use without G-CSF prophylaxis — neutropenia rate ~50%
Do NOT omit irinotecan pre-medication (atropine — cholinergic prevention)
Do NOT add anti-EGFR (cetuximab/panitumumab) — triplet + anti-EGFR vs triplet + bev not superior per MACBETH/VOLFI; use one or the other
Do NOT continue past disease progression — switch promptly to 2L

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · FOLFOX + Bevacizumab

14-day cycles × Until progression / unacceptable toxicity (mCRC 1L)

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

Aggressive plan

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

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

Standard plan

Induction · FOLFOX + Cetuximab

14-day cycles × Until progression / unacceptable toxicity

Aggressive plan

Induction · FOLFOXIRI + Bevacizumab

14-day cycles × Until progression / unacceptable toxicity; consider de-escalation after 4-6 months

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: 2/2 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-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)
SRC-TRIBE-LOUPAKIS-2014: FOLFOXIRI plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Treatment of Metastatic Colorectal Cancer (2014)
SRC-TRIBE2-CREMOLINI-2020: FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE2 study (2020)

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: 2026-05-12.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT05786924	Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies	PHASE1 / PHASE2	RECRUITING	Institut de Recherches Internationales Servier	—	Biomarker: enriched Surrogate endpoint only
NCT07446322	FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer	PHASE2	RECRUITING	Oncolytics Biotech	—	Surrogate endpoint only Single country
NCT06445062	Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors	PHASE1 / PHASE2	RECRUITING	Revolution Medicines, Inc.	—	Biomarker: enriched Single country
NCT07213570	STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer	PHASE2	RECRUITING	National Cancer Institute, Naples	—	Biomarker: enriched Surrogate endpoint only Single country
NCT05970302	XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC	PHASE2	RECRUITING	Cancer Institute and Hospital, Chinese Academy of Medical Sciences	—	Biomarker: enriched Surrogate endpoint only Single country
NCT06763029	Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced Colorectal Cancer	PHASE2	RECRUITING	Fudan University	—	Biomarker: enriched Small N (<50) Surrogate endpoint only Single country
NCT06229340	Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations	PHASE2	RECRUITING	N.N. Petrov National Medical Research Center of Oncology	—	Biomarker: enriched Small N (<50) Surrogate endpoint only Single country
NCT05727163	FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients	PHASE2	RECRUITING	Sun Yat-sen University	—	Surrogate endpoint only Single country
NCT06440902	Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA	PHASE2	RECRUITING	Fudan University	—	Biomarker: enriched Single country
NCT07201519	Study of Safety/Feasibility of a Hybrid Model of Tertiary and Community Delivery of Hepatic Artery Infusion Chemotherapy	PHASE2	RECRUITING	Michael J Cavnar, MD	—	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 FOLFOX + Bevacizumab (REG-FOLFOX-BEV)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan FOLFOX (mFOLFOX6) (REG-FOLFOX)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Pembrolizumab monotherapy (MSI-H mCRC 1L) (REG-PEMBROLIZUMAB-MSI-MONO)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan FOLFOX + Cetuximab (REG-FOLFOX-CETUX)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan FOLFOXIRI + Bevacizumab (REG-FOLFOXIRI-BEV)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT05786924 Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07446322 FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06445062 Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07213570 STREAM-2: Second-line Treatment With REgorafenib in Advanced RAS-Mutant Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05970302 XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06763029 Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced Colorectal Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06229340 Leflunomide or Combination of MEK Inhibitor and Hydroxychloroquine for Refractory Patients With RAS Mutations No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05727163 FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06440902 Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07201519 Study of Safety/Feasibility of a Hybrid Model of Tertiary and Community Delivery of Hepatic Artery Infusion Chemotherapy 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: 2026-05-12.

plan_id: PLAN-CRC-MET-RAS-MUT-1L-001-V1 | version: 1 | generated: 2026-05-12T18:41:26.896444+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.