Disfunção dos órgãos basais excluindo vandetanib padrão / cabozantinib multiquinase inhi...

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ID	`RF-MTC-ORGAN-DYSFUNCTION`
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	Baseline organ dysfunction precluding standard vandetanib / cabozantinib multikinase inhibitor or selpercatinib / pralsetinib RET-selective inhibitor in advanced MTC: QTc >480 ms (vandetanib + cabozantinib QT prolongation, FDA boxed warning for vandetanib), LVEF <50% (vandetanib / cabozantinib hypertension + cardiac dysfunction), CrCl <30 mL/min (TKI dose adjustment), bilirubin >3× ULN (TKI hepatic clearance), or uncontrolled hypertension.
Direcção clínica	de escalonamento
Categoria	disfunção de órgãos

Lógica de Desencadeamento

{
  "any_of": [
    {
      "comparator": ">",
      "finding": "qtc_ms",
      "threshold": 480
    },
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 50
    },
    {
      "comparator": "<",
      "finding": "creatinine_clearance_ml_min",
      "threshold": 30
    },
    {
      "comparator": ">=",
      "finding": "bilirubin_ratio_to_uln",
      "threshold": 3
    },
    {
      "finding": "uncontrolled_hypertension",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notas

Vandetanib carries FDA boxed warning for QT prolongation, sudden death, and torsades — baseline ECG mandatory; contraindicated if QTc >450 ms or bradycardia. Cabozantinib similar QT signal + GI perforation / fistula risk. Selective RET inhibitors (selpercatinib, pralsetinib) better tolerated but still carry hypertension, transaminitis, QT prolongation — selpercatinib LIBRETTO-531 vs vandetanib showed superior PFS + better safety profile, now preferred 1L. Selpercatinib hepatic dose reductions per FDA label. Uncontrolled hypertension is gating — optimize before TKI initiation.

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