Anaplastic thyroid carcinoma with actionable driver mutation: BRAF V600E (~25-40% ATC; da...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-THYROID-ANAPLASTIC-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-THYROID-ANAPLASTIC`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Red Flag Origin

Definition	Anaplastic thyroid carcinoma with actionable driver mutation: BRAF V600E (~25-40% ATC; dabrafenib + trametinib FDA-approved Cat 1 1L for BRAF-mutant ATC), NTRK fusion (rare; larotrectinib / entrectinib), RET fusion (rare; selpercatinib), or ALK fusion (very rare; alectinib / lorlatinib) — re-routes algorithm from emergency cytotoxic chemo + RT to targeted therapy with potential surgical resection after molecular response.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-BRAF-V600E",
      "value": "positive"
    },
    {
      "finding": "BIO-NTRK-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-RET",
      "value": "fusion"
    },
    {
      "finding": "BIO-ALK-FUSION",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

ATC is one of the most aggressive human malignancies (median OS 3-6 months historically). The discovery that ~25-40% are BRAF V600E- mutant transformed practice — dabrafenib + trametinib (ROAR basket) achieved ORR ~70% with median OS extended to ~14 mo in BRAF-mutant ATC, sometimes converting unresectable to resectable. NCCN Cat 1 recommendation; FDA approval 2018. For BRAF-mut ATC, neoadjuvant dabrafenib + trametinib → surgery → adjuvant RT is now the optimal paradigm when feasible. NTRK / RET / ALK fusions <5% combined but highly actionable. Comprehensive genomic profiling within days of diagnosis is critical given disease tempo. Priority bumped to 30 because targeted therapy is critical-tier override of cytotoxic default.

Used By

Red flag

RF-THYROID-ANAPLASTIC-FRAILTY-AGE - Age ≥75 with ECOG ≥2 or ≥2 comorbidities — cisplatin-paclitaxel CRT poorly tolerated and...