Baseline organ dysfunction precluding standard methotrexate / vinorelbine adjuvant or aff...

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ID	`RF-IMT-ORGAN-DYSFUNCTION`
Tipo	Sinal de alerta
Estado	reviewed 2026-04-27 \| pending_clinical_signoff
Doenças	`DIS-IMT`
Fontes	`SRC-NCCN-SARCOMA`

Origem da bandeira vermelha

Definição	Baseline organ dysfunction precluding standard methotrexate / vinorelbine adjuvant or affecting crizotinib / lorlatinib / entrectinib dosing in IMT: bilirubin >3× ULN (TKI-class hepatic clearance, vinorelbine metabolism), CrCl <30 mL/min (methotrexate contraindicated), LVEF <50% (lorlatinib hyperlipidemia + cardiac concerns), QTc >480 ms (crizotinib / lorlatinib QT prolongation), or DLCO <60% (crizotinib pneumonitis signal).
Direcção clínica	de escalonamento
Categoria	disfunção de órgãos

Lógica de Desencadeamento

{
  "any_of": [
    {
      "comparator": ">=",
      "finding": "bilirubin_ratio_to_uln",
      "threshold": 3
    },
    {
      "comparator": "<",
      "finding": "creatinine_clearance_ml_min",
      "threshold": 30
    },
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 50
    },
    {
      "comparator": ">",
      "finding": "qtc_ms",
      "threshold": 480
    },
    {
      "comparator": "<",
      "finding": "dlco_percent",
      "threshold": 60
    }
  ],
  "type": "lab_value"
}

Notas

Crizotinib + lorlatinib both prolong QTc — baseline ECG mandatory; hold if QTc >500 ms. Crizotinib has documented pneumonitis signal (~1-2% Gr3+) — DLCO <60% increases risk of clinically meaningful toxicity. Lorlatinib hyperlipidemia + weight gain + cognitive effects documented; baseline lipid panel + LVEF measurement recommended. Hepatic dose reductions per FDA labels for severe impairment. Methotrexate / vinorelbine adjuvant (used in fusion-negative or pre- TKI era IMT) requires standard cytotoxic monitoring.

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