Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
BMA-POLE_GERMLINE_POLYMERASE_PRO · Algorithm: ALGO-CRC-ADJUVANT
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-POLE-GERMLINE | POLE germline exonuclease-domain pathogenic (PPAP — polymerase proofreading–associated polyposis) | IIA | - SRC-NCCN-GENETIC-FAMILIAL-CRC-2025
Evidence cited from clinical guidelines; per-source evidence levels not yet structured. See Phase-2-of-CIViC-pivot for re-cite roadmap. | POLE germline pathogenic variants in the exonuclease (proofreading) domain cause polymerase proofreading–associated polyposis (PPAP) — characterized by attenuated/oligo-polyposis (typically <100 adenomas), early-onset colorectal cancer, elevated endometrial cancer risk in women, and characteristic ultramutator tumor phenotype (TMB >100 mut/Mb) with potential immunotherapy responsiveness. Confirmed-carrier surveillance protocol (Lynch-like; per NCCN Genetic/Familial CRC 2025): colonoscopy q1-2y starting age 20-25, EGD q3y from age 30, endometrial sampling + TVUS q1-2y from age 30-35 in women, urinalysis annual from 30 (overlap with Lynch organ spectrum). The ultramutator phenotype in POLE-mutant tumors predicts immunotherapy benefit (high TMB) — pembrolizumab is FDA- approved for TMB-high (≥10 mut/Mb) advanced solid tumors regardless of tissue; POLE-mutant CRC and endometrial benefit appears substantial in small series. ESCAT IIA (predisposition + tumor-phenotype actionability). | colonoscopy q1-2y starting age 20-25 with polypectomy
EGD q3y from age 30
endometrial sampling + TVUS q1-2y from age 30-35 (women)
annual urinalysis from age 30
for POLE-mutant advanced CRC / endometrial: pembrolizumab 200 mg q3w — high response rate in ultramutator setting (NCCN Category 1 for TMB-H or MSI-H)
cascade testing to first-degree relatives; specific to exonuclease-domain variants (Pro286Arg, Val411Leu most common) | - SRC-NCCN-GENETIC-FAMILIAL-CRC-2025
|
Primary current-line option
- Indication
- IND-CRC-ADJUVANT-STAGE2-HIGHRISK-FOLFOX
- 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
- Provisional current-line default from ALGO-CRC-ADJUVANT: step 1 did not select a treatment branch. Stage I — observation; Stage IV — metastatic algorithm applies.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CRC-ADJUVANT-STAGE3-FOLFOX
- 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
- Indication
- IND-CRC-ADJUVANT-STAGE3-CAPOX
- Regimen
- CAPOX (XELOX)
- Drugs + NSZU
- Oxaliplatin (DRUG-OXALIPLATIN) 130 mg/m² · IV over 2h, day 1 · IV ✓ NSZU covered
- Capecitabine (DRUG-CAPECITABINE) 1000 mg/m² · PO BID, days 1-14 · PO ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-CRC-ADJUVANT-STAGE2-HIGHRISK-FOLFOX)
- Do NOT offer adjuvant chemo to dMMR/MSI-H stage II — no benefit, possible harm
- Do NOT delay adjuvant beyond 8 weeks post-surgery
- Do NOT add bevacizumab — NSABP C-08 negative
- Do NOT continue oxaliplatin past Grade 2 functional neuropathy — switch to 5-FU/LV
- Do NOT apply IDEA 3-month CAPOX data to FOLFOX (not interchangeable for duration reduction)
Standard plan (IND-CRC-ADJUVANT-STAGE3-FOLFOX)
- Do NOT delay adjuvant beyond 8 weeks post-surgery if avoidable — diminishing benefit thereafter
- Do NOT continue oxaliplatin past Grade 2 functional neuropathy — switch to 5-FU/LV alone
- Do NOT add bevacizumab in adjuvant — NSABP C-08 negative, NOT a standard
Standard plan (IND-CRC-ADJUVANT-STAGE3-CAPOX)
- Do NOT use CAPOX if CrCl <30 mL/min — capecitabine renally cleared
- Do NOT add bevacizumab — adjuvant bevacizumab NSABP C-08 negative
- Do NOT apply IDEA 3-month data from CAPOX to FOLFOX (FOLFOX 3 mo was inferior)
- Do NOT delay adjuvant beyond 8 weeks post-surgery
- Do NOT continue oxaliplatin past Grade 2 functional neuropathy — switch to capecitabine alone
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard 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
Standard plan
Induction · CAPOX (XELOX)
21-day cycles × 8 cycles (6 mo) adjuvant stage III; 4 cycles (3 mo) low-risk T1-3 N1 per IDEA
MDT brief
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: 0/0 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BLM-CONFIRMED-CARRIER, RF-CASCADE-FAP-FDR-POSITIVE, RF-CASCADE-LYNCH-FDR-POSITIVE, RF-CHEK2-CONFIRMED-CARRIER, RF-CHEK2-FAMILY-HISTORY-SUSPICION, RF-CHRONIC-IBD-CROHNS-SPECIFIC-PREVENTION, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-CMMRD-CONFIRMED-CARRIER, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-CRC-BRAF-V600E-POOR-PROGNOSIS, RF-CRC-EMERGENCY-OBSTRUCTION-PERFORATION, RF-CRC-FRAILTY-AGE, RF-CRC-HER2-AMP-ACTIONABLE, RF-CRC-INFECTION-SCREENING, RF-CRC-MSI-H-ACTIONABILITY, RF-CRC-OLIGOMET-LIVER-DEFINITION, RF-CRC-RAS-MUTANT, RF-CRC-RAS-WT, RF-CRC-TRANSFORMATION-PROGRESSION, RF-CRONKHITE-CANADA-CONFIRMED, RF-FAP-CONFIRMED-CARRIER, RF-FAP-FAMILY-HISTORY-SUSPICION, RF-IBD-CRC-PREVENTION, RF-JPS-CONFIRMED-CARRIER, RF-LIFESTYLE-ALCOHOL-CANCER-PREVENTION, RF-LIFESTYLE-HIGH-RED-MEAT-CRC-PREVENTION, RF-LIFESTYLE-LOW-CALCIUM-VIT-D-CRC-PREVENTION, RF-LIFESTYLE-LOW-FIBER-CRC-PREVENTION, RF-LIFESTYLE-LOW-MEDITERRANEAN-DIET-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-PROCESSED-MEAT-PREVENTION, RF-LIFESTYLE-RED-MEAT-HIGH-INTAKE-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-LYNCH-CONFIRMED-CARRIER, RF-LYNCH-FAMILY-HISTORY-SUSPICION, RF-OCC-FIREFIGHTER-PREVENTION, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION, RF-PSC-CHOLANGIOCARCINOMA-PREVENTION
Technical MDT skill metadata (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 | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-ESMO-COLON-2024: ESMO CRC Clinical Practice Guideline (2024)
- SRC-IDEA-GROTHEY-2018: Duration of Adjuvant Chemotherapy for Stage III Colon Cancer (2018)
- SRC-MOSAIC-ANDRE-2004: Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer (2004)
- SRC-NCCN-COLON-2025: NCCN Colon / Rectal Cancer (v.4.2025)
Experimental options (clinical trials)
Last synced: 2026-08-03 · ctgov.
No active trials matched this scenario in ctgov.
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 FOLFOX (mFOLFOX6) (REG-FOLFOX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan FOLFOX (mFOLFOX6) (REG-FOLFOX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan CAPOX (XELOX) (REG-CAPOX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-03.