MTC progression on first-line RET-selective inhibitor (acquired RET solvent-front mutatio...

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ID	`RF-MTC-TRANSFORMATION-PROGRESSION`
Tipo	Sinal de alerta
Estado	reviewed 2026-04-27 \| pending_clinical_signoff
Doenças	`DIS-MTC`
Fontes	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Origem da bandeira vermelha

Definição	MTC progression on first-line RET-selective inhibitor (acquired RET solvent-front mutation G810R / G810S / G810C), rapid calcitonin doubling time (<6 months — adverse prognostic marker), new bone / liver / brain metastases, or symptomatic carcinoid-like diarrhea (calcitonin-driven, debilitating) — triggers switch to next-gen RET inhibitor (TPX-0046, vepafestinib in trials), cabozantinib re-challenge, or peptide receptor radionuclide therapy.
Direcção clínica	aguentar
Categoria	transformação-progressão

Lógica de Desencadeamento

{
  "any_of": [
    {
      "finding": "ret_solvent_front_mutation",
      "value": true
    },
    {
      "comparator": "<",
      "finding": "calcitonin_doubling_time_months",
      "threshold": 6
    },
    {
      "finding": "new_bone_liver_brain_mets",
      "value": true
    },
    {
      "finding": "carcinoid_diarrhea_symptomatic",
      "value": true
    }
  ],
  "type": "composite_clinical"
}

Notas

Calcitonin doubling time <6 months is a validated adverse prognostic marker (Barbet et al, JCEM 2005) — predicts rapid clinical progression and shorter OS; serves as biomarker-based progression signal even before RECIST. Acquired RET solvent-front mutations (G810R/S/C) are the dominant on-target resistance to selpercatinib / pralsetinib (~30% of progressors). Next-gen RET inhibitors (vepafestinib / TPX-0046; LOX-260) in trials. Cabozantinib re-challenge has limited but documented activity post-RET-selective failure. Carcinoid-like diarrhea (calcitonin-driven) is debilitating — somatostatin analogs (octreotide / lanreotide) for symptom control. PRRT (¹⁷⁷Lu- DOTATATE) for somatostatin-receptor-positive metastatic MTC.

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