Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-HCC-L2-HCC_SYSTEMIC_2L_CABOZANTINIB · Algorithm: ALGO-HCC-SYSTEMIC-2L
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. |
Primary current-line option
- Indication
- IND-HCC-SYSTEMIC-2L-CABOZANTINIB
- Regimen
- Cabozantinib (HCC, 2L)
- Drugs + NSZU
- Cabozantinib (DRUG-CABOZANTINIB) 60 mg PO once daily · Continuous daily dosing; do not take with food (≥1h before or ≥2h after meal) · PO ✗ Not registered in UA
- Reason
- Primary current-line option selected by ALGO-HCC-SYSTEMIC-2L at step 4.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-HCC-SYSTEMIC-2L-REGORAFENIB
- Regimen
- Regorafenib (HCC, 2L)
- Drugs + NSZU
- Regorafenib (DRUG-REGORAFENIB) 160 mg PO once daily with low-fat breakfast (< 600 kcal, < 30% fat) · Days 1–21 of 28-day cycle (3 weeks on, 1 week off) · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-HCC-SYSTEMIC-2L-RAMUCIRUMAB
- Regimen
- Ramucirumab (HCC, 2L high AFP)
- Drugs + NSZU
- Ramucirumab (DRUG-RAMUCIRUMAB) 8 mg/kg IV over 60 minutes, day 1 · Day 1 q14 days (every 2 weeks) · IV ⚠ Out-of-pocket
- 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.
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-BILIRUBIN-TOTAL | Total bilirubin | Critical | lab | — | all tracks |
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CHILD-PUGH-SCORE | Child-Pugh score | Critical | clinical_assessment | — | standard |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-CT-CAP | CT chest/abdomen/pelvis | Standard | imaging | — | all tracks |
| TEST-ECG-BASELINE | Baseline electrocardiogram | Standard | clinical_assessment | — | desired (standard) |
| TEST-URINE-PROTEIN | Urine protein assessment | Standard | 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).
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 - Frailty profile precluding intensified 1L systemic in HCC: ECOG ≥3, OR (age ≥75 + Child-Pugh B7 + sarcopenia), OR composite (Karnofsky <70 + active hepatic encephalopathy + albumin <2.8). Triggers BSC discussion + palliative-care referral; sorafenib reduced-dose (200 mg BID) acceptable for selected CP-A frail patients.
IMbrave150 + HIMALAYA both required ECOG ≤1 — frail elderly excluded from pivotal trials. Real-world: sorafenib 200 mg BID start with cautious escalation; lenvatinib body-weight-based dosing (8 mg if ≤60 kg). Best supportive care +…
RF-HCC-FRAILTY-AGESRC-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
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-HCC-SYSTEMIC-2L-CABOZANTINIB)
- Не призначати при Child-Pugh B/C — CELESTIAL включав тільки Child-Pugh A; гепатотоксичnoсть посилена при порушенno функції печінки
- Не приймати з їжею — кабозантиnoб приймати натщесерце (≥1 год до або ≥2 год після їжі)
- Не ігнорувати ЛФТ моnoторинг кожno 4 тижno — при HCC на тлі ЦП гепатотоксичnoсть може спричинити декомпенсацію
- Уникати сильних інгібіторів CYP3A4 — знизити дозу до 40 мг/день (кетоконазол, ітраконазол, ритонавір)
- Не призначати при нещодавньому (<6 місяців) тромбозі артерій — ризик тромботичних ускладнень
- Відрізняти REG-CABOZANTINIB-HCC (60 мг/день монотерапія) від REG-NIVO-CABO-RCC (40 мг/день у комбінації) — різno дози при різних показах
Standard plan (IND-HCC-SYSTEMIC-2L-REGORAFENIB)
- Не призначати якщо сорафеnoб був скасований через токсичnoсть (не прогресування) — RESORCE включав тільки соративно-переносимих пацієнтів; непереносимість сорафеnoбу передбачає вищу токсичnoсть регорафеnoбу
- Не призначати при Child-Pugh B/C — RESORCE включав тільки Child-Pugh A; гепатотоксичnoсть підвищена при порушенno функції печінки
- Не пропускати профілактичну крем з сечовиною для HFSR — Grade 3 HFSR є основною причиною зменшення дози (54% всіх ступеnoв)
- Не ігнорувати прийом їжі — регорафеnoб приймати під час сnoданку з низьким вмістом жиру; голодування або жирна їжа значно змінює AUC
- Не призначати при ECOG >1 — RESORCE включав ECOG 0-1
- Перевірити гепатотоксичnoсть: ЛФТ щотижнево перші 2 місяці — припинити при AST/ALT >5× ULN
Standard plan (IND-HCC-SYSTEMIC-2L-RAMUCIRUMAB)
- НІКОЛИ не призначати при АФП <400 нг/мл — FDA-схвалення біомаркерно-вибіркове; REACH-1 (unselected) НЕ показав ЗВ-переваги (HR 0.87, p=0.14)
- Не призначати при активnoй кровотечі або нелікованому варикозному розширенno вен — анти-VEGFR2 підвищує ризик кровотечі
- Не ігнорувати протеїнурію — UPCR моnoторинг кожno 4 тижno; призупинити при UPCR ≥2 г/добу
- Не призначати при Child-Pugh B/C — REACH-2 включав тільки Child-Pugh A
- Контроль АТ перед кожним введенням — цільовий <150/100; гіпертензія у ~13% Grade 3-4
- Не призначати в Україno без підтвердження доступності — рамуцирумаб не зареєстрований в Україno
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Cabozantinib (HCC, 2L)
28-day cycles × Continue until progression or unacceptable toxicity; continuous daily dosing
Standard plan
Induction · Regorafenib (HCC, 2L)
28-day cycles × Continue until progression or unacceptable toxicity; 3-weeks-on/1-week-off schedule
Standard plan
Induction · Ramucirumab (HCC, 2L high AFP)
14-day cycles × Continue until progression or unacceptable toxicity
MDT brief
Discussion questions (2, 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
OQ-BIOMARKER-AFP
What is the status of Alpha-fetoprotein (serum) (BIO-AFP)? It is required by track(s): IND-HCC-SYSTEMIC-2L-RAMUCIRUMAB. Expected value: AFP ≥ 400 ng/mL (serum AFP; FDA label requirement for ramucirumab in HCC).
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 (4 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | medical_oncologist | Biomarker status | What is the status of Alpha-fetoprotein (serum) (BIO-AFP)? It is required by track(s): IND-HCC-SYSTEMIC-2L-RAMUCIRUMAB. Expected value: AFP ≥ 400 ng/mL (serum AFP; FDA label requirement for ramucirumab in HCC). |
| 3 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
| 4 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
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: 0/1 known (0%), 1 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
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-AFP | Alpha-fetoprotein (serum) | medical_oncologist | no | IND-HCC-SYSTEMIC-2L-RAMUCIRUMAB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: AFP ≥ 400 ng/mL (serum AFP; FDA label requirement for ramucirumab in HCC) |
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 | 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-CELESTIAL-ABOU-ALFA-2018: Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma ()
- SRC-NCCN-HCC-2025: NCCN Hepatocellular Carcinoma (v.3.2025)
- SRC-REACH2-ZHU-2019: Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial ()
- SRC-RESORCE-BRUIX-2017: Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial ()
Experimental options (clinical trials)
Last synced: 2026-09-09 · 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 |
|---|
| Aggressive plan Cabozantinib (HCC, 2L) (REG-CABOZANTINIB-HCC) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Regorafenib (HCC, 2L) (REG-REGORAFENIB-HCC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Ramucirumab (HCC, 2L high AFP) (REG-RAMUCIRUMAB-HCC) 1/1 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-09-09.