Patient
BMA-HNF1A_HCC · Algorithm: ALGO-HCC-SYSTEMIC-1L
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-HNF1A | HNF1A somatic mutation in hepatocellular carcinoma and hepatocellular adenoma (H-subtype); diagnostic/risk-stratification marker; no HNF1A-directed systemic therapy | IIB | - SRC-NCCN-HCC-2025: Level Category 2A (Supports, Sensitivity/Response)
- SRC-AASLD-HCC-2023: Level B (Supports, Sensitivity/Response)
| HNF1A somatic inactivating mutations occur in ~10% of HCC and ~35–40% of hepatocellular adenoma (H-subtype, H-HCA). Clinical utility: (1) HCA subtyping: biallelic HNF1A inactivation defines the H-HCA subtype characterized
by steatotic hepatocytes, LFABP (liver fatty acid binding protein) loss by IHC, and
very low malignant transformation risk (<1%). H-HCA management: surveillance rather
than resection for lesions <5 cm in women who discontinue oral contraceptives; resection
for >5 cm or persistent growth.
(2) HCC context: somatic HNF1A mutation in HCC is associated with preserved hepatocyte
differentiation phenotype (low AFP, well-differentiated histology) but does not select
systemic therapy. Standard HCC management applies: lenvatinib or sorafenib 1L; atezolizumab
+ bevacizumab (IMbrave150) preferred 1L for Child-Pugh A patients without contraindications.
(3) Germline HNF1A (MODY3): not an HCC risk factor; separate clinical context (diabetes
management), not oncologically relevant in HCC.
ESCAT IIB: HNF1A mutation is a validated diagnostic/risk-stratification marker for HCA subtyping with management implications; no therapeutic target in HCC. | Atezolizumab 1200 mg + bevacizumab 15 mg/kg IV q3w — preferred 1L advanced HCC (Child-Pugh A, ECOG 0–1; IMbrave150 OS HR 0.66; not HNF1A-specific)
Lenvatinib 12 mg (≥60 kg) or 8 mg (<60 kg) PO QD — 1L alternative HCC (REFLECT; non-inferior to sorafenib; not HNF1A-specific)
Hepatic surveillance (MRI liver q6m) ± resection for H-HCA >5 cm or growth — HNF1A-inactivated HCA management (LFABP IHC surrogate; low malignant risk) | - SRC-NCCN-HCC-2025
- SRC-AASLD-HCC-2023
|
Treatment options (3 tracks)
- Indication
- IND-HCC-SYSTEMIC-1L-ATEZO-BEV
- Regimen
- Atezolizumab + Bevacizumab
- Drugs + NSZU
- Atezolizumab (DRUG-ATEZOLIZUMAB) 1200 mg · IV q3w · IV ⚠ NSZU — not for this indication
- Bevacizumab (DRUG-BEVACIZUMAB) 15 mg/kg · IV q3w (concurrent) · IV ⚠ NSZU — not for this indication
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- Reason
- Engine default per algorithm ALGO-HCC-SYSTEMIC-1L: {'step': 3, 'outcome': True, 'branch': {'result': 'IND-HCC-SYSTEMIC-1L-ATEZO-BEV'}, 'fired_red_flags': ['RF-FITNESS-ECOG-FIT'], 'winner_red_flag': 'RF-FITNESS-ECOG-FIT'}
- Indication
- IND-HCC-SYSTEMIC-1L-DURVA-TREME
- Regimen
- Durvalumab + Tremelimumab (STRIDE)
- Drugs + NSZU
- Tremelimumab (DRUG-TREMELIMUMAB) 300 mg · IV — single priming dose only (cycle 1 day 1) · IV ✗ Not registered in UA
- Durvalumab (DRUG-DURVALUMAB) 1500 mg · IV q4w (cycle 1 with tremelimumab; subsequent cycles mono) · IV ⚠ NSZU — not for this indication
- Hard contraindications
- CI-PEMBROLIZUMAB-AUTOIMMUNE
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-HCC-SYSTEMIC-1L-SORAFENIB
- Regimen
- Sorafenib monotherapy
- Drugs + NSZU
- Sorafenib (DRUG-SORAFENIB) 400 mg PO BID (start 200 mg BID; escalate to 400 mg if tolerated) · Continuous · PO ⚠ NSZU — not for this indication
- Reason
- Alternative track presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 3 → branch IND-HCC-SYSTEMIC-1L-ATEZO-BEV
- RF-FITNESS-ECOG-FIT ★ winner: 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).
SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-AFP | AFP serum | Critical | lab | CSD Lab: B001 | all tracks |
| TEST-CHILD-PUGH-CALCULATION | Child-Pugh classification calculation | Critical | clinical_assessment | — | all tracks |
| TEST-CT-CHEST-ABDOMEN-PELVIS | CT chest + abdomen + pelvis with IV contrast | Critical | imaging | — | all tracks |
| TEST-EGD-VARICES-SCREENING | Esophagogastroduodenoscopy with varices assessment | Critical | imaging | — | standard |
| TEST-HBV-SEROLOGY | Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs) | Critical | lab | — | standard |
| TEST-HCV-ANTIBODY | HCV Antibody | Critical | lab | — | standard |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | standard |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Child-Pugh B or C cirrhosis in HCC patient. CP-A is the only fully- studied class for ICI combinations (atezo+bev, durva+treme); CP-B has partial sorafenib/lenvatinib data but worse safety; CP-C generally precludes systemic therapy (focus on supportive care + transplant evaluation if liver-limited disease).
RF-HCC-CHILD-PUGH-B-C
- Active or recent (≤6 months) variceal hemorrhage in HCC patient with cirrhosis. Mandates EGD assessment + variceal band ligation BEFORE any bevacizumab-containing regimen (atezo+bev, IMbrave150 prerequisite). Active bleeding is an absolute hold on systemic therapy until controlled.
RF-HCC-VARICEAL-BLEED
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-HCC-SYSTEMIC-1L-ATEZO-BEV)
- Do NOT initiate without EGD within 6 months — high-risk varices must be ligated/banded first (perforation/bleed risk)
- Do NOT use in Child-Pugh B/C — atezo+bev not studied; mortality risk
- Do NOT skip HBV prophylaxis in HBsAg+ / anti-HBc+ patients (entecavir or TDF) — HBV reactivation reported under anti-VEGF + ICI; continue ≥12 mo post-therapy
- Do NOT delay HCV-DAA in HCV-RNA+ patients — initiate sofosbuvir/velpatasvir before or concurrently with atezo+bev; SVR12 reduces decompensation risk and may improve OS in HCC-on-HCV-cirrhosis
- Do NOT combine sofosbuvir with amiodarone — severe bradycardia / cardiac arrest
- Do NOT continue bevacizumab through Grade 3+ HTN or proteinuria >3.5 g/24h
Aggressive plan (IND-HCC-SYSTEMIC-1L-DURVA-TREME)
- Do NOT use in Child-Pugh B/C
- Do NOT skip HBV prophylaxis
- Do NOT continue through Grade 3+ irAE without permanent discontinuation consideration (CTLA-4 colitis can be fatal)
Standard plan (IND-HCC-SYSTEMIC-1L-SORAFENIB)
- Do NOT continue through hepatic decompensation onset
- Do NOT delay HFSR prophylaxis (urea cream, emollient, friction avoidance)
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Atezolizumab + Bevacizumab
21-day cycles × Until progression / unacceptable toxicity
Aggressive plan
Induction · Durvalumab + Tremelimumab (STR
28-day cycles × Until progression / unacceptable toxicity
MDT brief
Skills (recommended) — for consideration (1)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Open questions (1, 0 blocking)
Data quality
- Unevaluated RedFlags: RF-HCC-AFP-RAPID-RISE, RF-HCC-CHILD-PUGH-B-C, RF-HCC-FRAILTY-AGE, RF-HCC-HBV-REACTIVATION-RISK, RF-HCC-HIGH-RISK-BIOLOGY, RF-HCC-VARICEAL-BLEED
Skill catalog (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 | 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-AASLD-HCC-2023: AASLD Practice Guidance on HCC (2023)
- SRC-HIMALAYA-ABOU-ALFA-2022: (not in KB)
- SRC-IMBRAVE150-FINN-2020: (not in KB)
- SRC-NCCN-HCC-2025: NCCN Hepatocellular Carcinoma (v.3.2025)
Experimental options (clinical trials)
Last synced: 2026-05-04 · 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 Atezolizumab + Bevacizumab (REG-ATEZO-BEV) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Durvalumab + Tremelimumab (STRIDE) (REG-DURVA-TREME-STRIDE) 1/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Sorafenib monotherapy (REG-SORAFENIB-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.