Patient
BMA-BRAF_V600E_THYROID_ANAPLASTI · Algorithm: ALGO-THYROID-ANAPLASTIC-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-BRAF-V600E | V600E (exon 15, kinase domain — present in ~25-50% of anaplastic thyroid carcinoma) | IA | | BRAF V600E in anaplastic thyroid carcinoma (ATC, ~25-50% of cases): dabrafenib + trametinib has tumor-agnostic FDA approval for BRAF V600E unresectable/metastatic disease and is preferred 1L for V600E-mutant ATC per SRC-NCCN-THYROID-2025. The pivotal ROAR basket trial (Subbiah JCO 2018 — ATC cohort ORR 69%, mOS ~14 mo, dramatic response in a historically rapid-fatal disease — historical mOS ~5 mo) drove the 2018 FDA accelerated approval (full conversion 2022 with pan-cancer broadening). Consider neoadjuvant dabrafenib+trametinib to enable surgery in initially unresectable V600E ATC per SRC-NCCN-THYROID-2025. | dabrafenib + trametinib (1L V600E ATC per SRC-NCCN-THYROID-2025)
neoadjuvant dabrafenib + trametinib → surgery → adjuvant systemic ± RT (initially unresectable, per SRC-NCCN-THYROID-2025) | |
Treatment options (2 tracks)
- Indication
- IND-ATC-PACLITAXEL-CARBOPLATIN
- Regimen
- Paclitaxel + carboplatin (ATC, palliative 1L)
- Drugs + NSZU
- Paclitaxel (DRUG-PACLITAXEL) Paclitaxel 175 mg/m² · Per regimen schedule · IV ✓ NSZU covered
- Carboplatin (DRUG-CARBOPLATIN) carboplatin AUC 5 IV q3w · Per regimen schedule · IV ⚠ NSZU — not for this indication
- Reason
- Engine default per algorithm ALGO-THYROID-ANAPLASTIC-1L: {'step': 3, 'outcome': True, 'branch': {'result': 'IND-ATC-PACLITAXEL-CARBOPLATIN', 'notes': 'BRAF wild-type / non-V600E / unknown + ECOG 0-2: palliative paclitaxel+carboplatin chemotherapy (historical 1L ATC; mOS ~5-6 mo). If V600E result still pending, begin chemotherapy and switch to dabrafenib+trametinib immediately upon V600E confirmation. Lenvatinib±pembrolizumab (KEYNOTE-B54 emerging) is investigational. Clinical trial enrollment preferred.\n'}, 'fired_red_flags': ['RF-FITNESS-ECOG-FIT'], 'winner_red_flag': 'RF-FITNESS-ECOG-FIT'}
- Indication
- IND-ATC-BRAF-V600E-DAB-TRAM
- Regimen
- —
- 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-ATC-PACLITAXEL-CARBOPLATIN
- 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-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| 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-BRAF-V600E-MUTATION | TEST-BRAF-V600E-MUTATION | Standard | — | — | all tracks |
| TEST-BRAIN-MRI-CONTRAST | Brain MRI with contrast | Standard | — | — | desired (standard) |
| TEST-CT-NECK-THORAX-ABDOMEN-PELVIS | TEST-CT-NECK-THORAX-ABDOMEN-PELVIS | Standard | — | — | all tracks |
| TEST-ECG-BASELINE | TEST-ECG-BASELINE | Standard | — | — | all tracks |
| TEST-LVEF-ECHO | TEST-LVEF-ECHO | Standard | — | — | all tracks |
| TEST-OPHTHALMOLOGIC-EXAM | TEST-OPHTHALMOLOGIC-EXAM | Standard | — | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Age ≥75 with ECOG ≥2 or ≥2 comorbidities — cisplatin-paclitaxel CRT poorly tolerated and curative-intent surgical resection often not feasible; for BRAF-mutant ATC, dabrafenib + trametinib monotherapy (without RT or surgery) is reasonable; for BRAF-wild-type frail patients, palliative-intent care + tracheostomy for airway management is often the appropriate path. ATC frailty assessment must integrate with palliative-care planning given short median OS.
RF-THYROID-ANAPLASTIC-FRAILTY-AGE
- Active or latent infection requiring resolution / prophylaxis before initiating cisplatin / paclitaxel / doxorubicin chemoradiation, dabrafenib + trametinib, larotrectinib / entrectinib, or selpercatinib for ATC: HBsAg-positive (HBV reactivation on cytotoxic + targeted), anti-HBc-positive (occult HBV), HIV-positive (ART coordination, CYP3A4 interactions with TKIs), or active TB. Disease tempo limits ability to fully resolve infection — pragmatic prophylaxis approach required.
RF-THYROID-ANAPLASTIC-INFECTION-SCREENING
- Baseline organ dysfunction precluding standard cisplatin / paclitaxel / doxorubicin chemoradiation or affecting BRAF-MEK-inhibitor dosing in ATC: CrCl <30 mL/min (cisplatin contraindicated), LVEF <50% (doxorubicin contraindicated; trametinib cardiac monitoring), bilirubin >3× ULN (BRAFi/MEKi hepatic clearance), QTc >480 ms (dabrafenib QT signal), or compromised airway from tumor (tracheostomy or stent required before systemic therapy initiation).
RF-THYROID-ANAPLASTIC-ORGAN-DYSFUNCTION
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-ATC-BRAF-V600E-DAB-TRAM)
- НІКОЛИ не призначати дабрафеніб без траметинібу — монотерапія BRAFi при BRAF V600E ATC викликає парадоксальну активацію MAPK та може прискорити ріст пухлини
- Не відкладати тестування BRAF V600E — ініціювати в день отримання матеріалу біопсії (RAID-протокол); ATC — швидко прогресуюча хвороба
- Не призначати при BRAF V600 дикого типу або не-V600E мутації (BRAF клас 2/3) — інша мішень, BRAFi неефективний
- Не починати при QTc >500 мс або LVEF нижче нижньої межі норми — кардіологічна оцінка обов'язкова перед початком
- Не пропускати дерматологічний огляд кожні 4-8 тижнів — шкірний плоскоклітинний рак / кератоакантома є класовим ефектом BRAFi
- Не відкладати хірургічну консультацію при хорошій відповіді — мета неоад'ювантної терапії: конверсія до резектабельності
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Paclitaxel + carboplatin (ATC,
21-day cycles × 6 cycles or until progression / toxicity
MDT brief
Skills (recommended) — for consideration (1)
Data quality
- Unevaluated RedFlags: RF-ATC-BRAF-V600E-ACTIONABLE, RF-THYROID-ANAPLASTIC-FRAILTY-AGE, RF-THYROID-ANAPLASTIC-HIGH-RISK-BIOLOGY, RF-THYROID-ANAPLASTIC-INFECTION-SCREENING, RF-THYROID-ANAPLASTIC-ORGAN-DYSFUNCTION, RF-THYROID-ANAPLASTIC-TRANSFORMATION-PROGRESSION
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-NCCN-THYROID-2025: NCCN Clinical Practice Guidelines — Thyroid Carcinoma (2025.v2)
- SRC-ROAR-SUBBIAH-2018: (not in KB)
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: 2026-05-04.
| NCT | Title | Phase | Status | Sponsor | UA | Eligibility (excerpt) |
|---|
| NCT06902376 | XL092 and Cemiplimab in BRAF WT Thyroid Cancer | PHASE1 | RECRUITING | — | |
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 |
|---|
| Standard plan Paclitaxel + carboplatin (ATC, palliative 1L) (REG-PACLITAXEL-CARBOPLATIN-ATC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan — No regimen components on this track — availability unknown | — unknown | — unknown | ₴-? — verify pathway | not recorded |
| Trial · NCT06902376 XL092 and Cemiplimab in BRAF WT Thyroid Cancer 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: 2026-05-04.