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OpenOnco · DIS-HCC · BIO-HNF1A (ESCAT IIB)
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Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
OpenOnco · Treatment Plan
Treatment plan — Hepatocellular carcinoma
PLAN-BMA-HNF1A_HCC-V1 · v1 · 2026-08-17
Patient
BMA-HNF1A_HCC · Algorithm: ALGO-HCC-SYSTEMIC-1L
DiagnosisHepatocellular carcinoma
MOH / ICD-10C22.0
ICD-O-38170/3; C22.0

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
ESCAT: clinical review pendingBIO-HNF1AHNF1A somatic mutation in hepatocellular carcinoma and hepatocellular adenoma (H-subtype); diagnostic/risk-stratification marker; no HNF1A-directed systemic therapyIIB
Standard care
  • 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

Primary current-line option

Standard plan
★ DEFAULT
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
Primary current-line option selected by ALGO-HCC-SYSTEMIC-1L at step 3; branch-driving red flag: RF-FITNESS-ECOG-FIT.

Other current-line alternatives (2 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
Aggressive plan
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
Current-line alternative presented for HCP consideration
Standard plan
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
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 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
IDNamePriorityCategoryWhere to orderNeeded for
TEST-AFPAFP serumCriticallabCSD Lab: B001all tracks
TEST-CHILD-PUGH-CALCULATIONChild-Pugh classification calculationCriticalclinical_assessment—all tracks
TEST-CT-CHEST-ABDOMEN-PELVISCT chest + abdomen + pelvis with IV contrastCriticalimaging—all tracks
TEST-EGD-VARICES-SCREENINGEsophagogastroduodenoscopy with varices assessmentCriticalimaging—standard
TEST-HBV-SEROLOGYHepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)Criticallab—standard
TEST-HCV-ANTIBODYHCV AntibodyCriticallab—standard
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallab—standard

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).
    Pre-existing autoimmune disease is present in ~10-15% of patients eligible for ICI therapy; historically excluded from pivotal trials. Real-world data (Abdel-Wahab 2018, 3557 pts) shows 55% experienced irAE flare and ~29% required…
    RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISKSRC-SITC-ICI-IRAEMANAGEMENT-2021SRC-ESMO-ICI-TOXICITY-2022
  • 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).
    Child-Pugh score assesses encephalopathy, ascites, bilirubin, albumin, INR. CP-B: ICI-bev contraindicated (anti-angiogenic stress on decompensated liver); sorafenib partial data (GIDEON registry). CP-C: best supportive care + hepatology /…
    RF-HCC-CHILD-PUGH-B-CSRC-NCCN-HCC-2025SRC-AASLD-HCC-2023
  • 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.
    IMbrave150 explicitly excluded patients with high-risk varices not treated by ligation/banding. Routes patient to durva+treme (STRIDE) alternative (HIMALAYA — no bev exposure) OR to TKI (sorafenib / lenvatinib) alone if anti-angiogenic…
    RF-HCC-VARICEAL-BLEEDSRC-NCCN-HCC-2025SRC-AASLD-HCC-2023

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 (STRIDE)
28-day cycles × Until progression / unacceptable toxicity

MDT brief

Discussion questions (2, 1 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
  • BLOCKING OQ-BIOMARKER-AFP
    What is the status of Alpha-fetoprotein (serum) (BIO-AFP)? It is required by track(s): IND-HCC-SYSTEMIC-1L-ATEZO-BEV, IND-HCC-SYSTEMIC-1L-DURVA-TREME, IND-HCC-SYSTEMIC-1L-SORAFENIB. Expected value: AFP baseline (ng/mL) — required as risk-stratifier and treatment-response marker; AFP-high subgroup (>400) showed comparable atezo-bev OS benefit per IMbrave150 subgroup analysis.
    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.
    → medical_oncologist

MDT talk tree (3 steps)

#OwnerTopicAction
1medical_oncologistBiomarker status BLOCKINGWhat is the status of Alpha-fetoprotein (serum) (BIO-AFP)? It is required by track(s): IND-HCC-SYSTEMIC-1L-ATEZO-BEV, IND-HCC-SYSTEMIC-1L-DURVA-TREME, IND-HCC-SYSTEMIC-1L-SORAFENIB. Expected value: AFP baseline (ng/mL) — required as risk-stratifier and treatment-response marker; AFP-high subgroup (>400) showed comparable atezo-bev OS benefit per IMbrave150 subgroup analysis.
2hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
3clinical_pharmacistSpecialist 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

Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.
  • Biomarker coverage: 2/3 known (67%), 1 missing, 1 default-track gaps
  • Unevaluated RedFlags: RF-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION, RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-CASCADE-VHL-FDR-POSITIVE, RF-CHRONIC-CIRRHOSIS-ETIOLOGY-AGNOSTIC-HCC-PREVENTION, RF-CHRONIC-HBV-MALIGNANCY-PREVENTION, RF-CHRONIC-NAFLD-MASLD-HCC-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, 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, RF-HEMOCHROMATOSIS-HCC-PREVENTION, RF-LIFESTYLE-ALCOHOL-CANCER-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-TOBACCO-CANCER-PREVENTION, RF-OCC-VINYL-CHLORIDE-MALIGNANCY-PREVENTION, RF-PSC-CHOLANGIOCARCINOMA-PREVENTION, RF-VHL-CONFIRMED-CARRIER, RF-WILSONS-DISEASE-HCC-PREVENTION
Missing biomarkerLabelMDT ownerDefault trackRequired byNext action
BIO-AFPAlpha-fetoprotein (serum)medical_oncologistyesIND-HCC-SYSTEMIC-1L-ATEZO-BEV, IND-HCC-SYSTEMIC-1L-DURVA-TREME, IND-HCC-SYSTEMIC-1L-SORAFENIBVerify result, method, specimen, and report date before sign-off. Expected/constraint: AFP baseline (ng/mL) — required as risk-stratifier and treatment-response marker; AFP-high subgroup (>400) showed comparable atezo-bev OS benefit per IMbrave150 subgroup analysis
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).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

Experimental options (clinical trials)

Last synced: 2026-08-17 · 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).
OptionUA registrationNSZUCost orientationAccess pathway
Standard plan
Atezolizumab + Bevacizumab (REG-ATEZO-BEV)
✓ registered✓ covered₴-? — verify pathwayNSZU 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 pathwaynot recorded
Standard plan
Sorafenib monotherapy (REG-SORAFENIB-MONO)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-17.

plan_id: PLAN-BMA-HNF1A_HCC-V1 | version: 1 | generated: 2026-08-17T08:06:31.774236+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.