Papillary thyroid carcinoma with adverse molecular / clinical features: BRAF V600E (~60%...

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ID	`RF-THYROID-PAPILLARY-HIGH-RISK-BIOLOGY`
Тип	Тривожна ознака
Статус	переглянуто 2026-04-27 \| очікує клінічного підпису
Хвороби	`DIS-THYROID-PAPILLARY`
Джерела	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Походження тривожної ознаки

Визначення	Papillary thyroid carcinoma with adverse molecular / clinical features: BRAF V600E (~60% of PTC, more aggressive when paired with TERT promoter mutation), TERT promoter mutation (~10%, strongly adverse — 5-yr OS <50% in advanced), TP53 mutation (rare, dedifferentiation risk), NTRK / RET / ALK fusion (rare in PTC; targeted therapy candidate), radioactive-iodine (RAI)-refractory metastatic disease, or aggressive histologic variant (tall cell, columnar, hobnail) — re-routes to multikinase inhibitor (lenvatinib / sorafenib) or selective TKI (selpercatinib / larotrectinib / dabrafenib).
Клінічний напрям	intensify
Категорія	high-risk-biology

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "BIO-BRAF-V600E",
      "value": "positive"
    },
    {
      "finding": "tert_promoter_mutation",
      "value": true
    },
    {
      "finding": "BIO-TP53-MUTATION",
      "value": "positive"
    },
    {
      "finding": "BIO-NTRK-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-RET",
      "value": "fusion"
    },
    {
      "finding": "BIO-ALK-FUSION",
      "value": "positive"
    },
    {
      "finding": "rai_refractory",
      "value": true
    },
    {
      "finding": "aggressive_histology_variant",
      "value": true
    }
  ],
  "type": "biomarker"
}

Нотатки

Most PTC is indolent (10-yr OS >95%) — high-risk biology flag is about identifying the ~5-10% who will have aggressive course. BRAF V600E + TERT promoter co-mutation is the strongest adverse molecular signature (Liu et al, JCO 2017 — meta-analysis 5-yr OS hazard ratio ~3-4). RAI-refractory disease (no iodine uptake on diagnostic scan, progression on therapeutic activities ≥600 mCi cumulative) → lenvatinib (SELECT trial PFS 18 vs 4 mo). RET-fusion PTC (~10% of pediatric / young adult) → selpercatinib (LIBRETTO-001) preferred over multikinase. NTRK- fusion PTC → larotrectinib (NCCN tumor-agnostic). BRAF-mut RAI-refractory → dabrafenib + trametinib (off-label, but data emerging). Aggressive variants (tall cell ~10%, columnar, hobnail) more often BRAF+ and RAI-refractory.

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