Patient
VERIFIED-HCC-L1-HCC_SYSTEMIC_1L_DURVA_TREME · 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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-AFP | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- 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
- Primary current-line option selected by ALGO-HCC-SYSTEMIC-1L at step 1; branch-driving red flag: RF-HCC-VARICEAL-BLEED.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- 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
- Current-line alternative 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
- 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-HCC-SYSTEMIC-1L-DURVA-TREME
- RF-HCC-VARICEAL-BLEED ★ winner: 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.
SRC-NCCN-HCC-2025SRC-AASLD-HCC-2023
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
- 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
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-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
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
Aggressive plan
Induction · Durvalumab + Tremelimumab (STRIDE)
28-day cycles × Until progression / unacceptable toxicity
Standard plan
Induction · Atezolizumab + Bevacizumab
21-day cycles × Until progression / unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (2 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. |
Skills (recommended) — for consideration (1)
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: 3/3 known (100%), 0 missing, 0 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
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).
| 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: Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma ()
- SRC-IMBRAVE150-FINN-2020: Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma ()
- SRC-NCCN-HCC-2025: NCCN Hepatocellular Carcinoma (v.3.2025)
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: 2026-07-15.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06311929 | Precision Adjuvant Therapy After Surgery for Hepatocellular Carcinoma | PHASE4 | RECRUITING | — | Surrogate endpoint only Single country | |
| NCT06383520 | Study on the Clinical Application Value of PET Imaging Targeting GPC3 in Hepatocellular Carcinoma | EARLY_PHASE1 | RECRUITING | — | Single country | |
| NCT06718153 | Immunohistochemical Algorithm for the Diagnosis and Classification of Hepatocellular Carcinomas With TERT, TP53 and CTNNB1 Mutation | NA | RECRUITING | — | Single country | |
| NCT07118202 | TheraBionic P1 Device in Subjects With Advanced Hepatocellular Carcinoma | NA | RECRUITING | — | Single country | |
| NCT04912765 | Neoantigen Dendritic Cell Vaccine and Nivolumab in HCC and Liver Metastases From CRC | PHASE2 | RECRUITING | — | Single country | |
| NCT04150744 | RFA Plus Carrizumab vs Carrizumab Alone for HCC | PHASE2 | RECRUITING | — | Surrogate endpoint only Single country | |
| NCT07285044 | The Cancer Connected Access and Remote Expertise Beyond Walls Program to Provide In-Home Cancer Treatment and Improve Treatment Satisfaction in Cancer Patients Living in the Florida Panhandle and Surrounding Areas | PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT07123545 | Autologous Neoantigen-Specific T-Cell Therapy for Advanced Hepatocellular Carcinoma | PHASE1 / PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT03959800 | Molecular Basis of Pediatric Liver Cancer | N/A | RECRUITING | — | Single country | |
| NCT06904170 | Durvalumab and Tremelimumab With or Without Hepatic Arterial Infusion of Chemotherapy in Hepatocellular Carcinoma | PHASE2 / PHASE3 | RECRUITING | — | 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 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 Atezolizumab + Bevacizumab (REG-ATEZO-BEV) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Sorafenib monotherapy (REG-SORAFENIB-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT06311929 Precision Adjuvant Therapy After Surgery for Hepatocellular Carcinoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06383520 Study on the Clinical Application Value of PET Imaging Targeting GPC3 in Hepatocellular Carcinoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06718153 Immunohistochemical Algorithm for the Diagnosis and Classification of Hepatocellular Carcinomas With TERT, TP53 and CTNNB1 Mutation No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07118202 TheraBionic P1 Device in Subjects With Advanced Hepatocellular Carcinoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04912765 Neoantigen Dendritic Cell Vaccine and Nivolumab in HCC and Liver Metastases From CRC No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04150744 RFA Plus Carrizumab vs Carrizumab Alone for HCC No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07285044 The Cancer Connected Access and Remote Expertise Beyond Walls Program to Provide In-Home Cancer Treatment and Improve Treatment Satisfaction in Cancer Patients Living in the Florida Panhandle and Surrounding Areas No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07123545 Autologous Neoantigen-Specific T-Cell Therapy for Advanced Hepatocellular Carcinoma No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT03959800 Molecular Basis of Pediatric Liver Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06904170 Durvalumab and Tremelimumab With or Without Hepatic Arterial Infusion of Chemotherapy in Hepatocellular Carcinoma 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: 2026-07-15.