Progression du CTM sur inhibiteur sélectif RET de première ligne (mutation avant solvant RET...

Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.

ID	`RF-MTC-TRANSFORMATION-PROGRESSION`
Type	Signal d’alerte
État	reviewed 2026-04-27 \| pending_clinical_signoff
Maladies	`DIS-MTC`
Sources	`SRC-ATA-THYROID-2015` `SRC-NCCN-THYROID-2025`

Origine du drapeau rouge

Définition	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.
Direction clinique	en attente
Catégorie	transformation-progression

Logique de déclenchement

{
  "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"
}

Notes

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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