Baseline organ dysfunction in pediatric IFS precluding standard VAC (vincristine / actino...

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

Origem da bandeira vermelha

Definição	Baseline organ dysfunction in pediatric IFS precluding standard VAC (vincristine / actinomycin / cyclophosphamide) cytotoxic adjuvant or affecting larotrectinib / entrectinib dosing: bilirubin >3× ULN (vincristine / TRK-inhibitor hepatic clearance), CrCl <30 mL/min for age-adjusted GFR (cyclophosphamide dose adjustment), severe cytopenias (ANC <1.0, platelets <80), or LVEF <55% (anthracycline-component protocols, e.g., VAC-doxorubicin escalation).
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": "anc_x10_9_per_l",
      "threshold": 1.0
    },
    {
      "comparator": "<",
      "finding": "platelets_x10_9_per_l",
      "threshold": 80
    },
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 55
    }
  ],
  "type": "lab_value"
}

Notas

Pediatric VAC + IE (Ewing-like) protocols are myelosuppressive and require strict hepatic / renal monitoring in infants (often <1 yr old). LVEF threshold 55% (not 50%) in pediatric oncology reflects long-life-expectancy sensitivity to anthracycline cardiotoxicity. Larotrectinib / entrectinib much better tolerated than cytotoxic in this age group — the organ-dysfunction flag pushes harder toward TRK-inhibitor monotherapy when fusion-positive (which is >90% of cases). For TRK-inhibitor: dose by BSA / weight per FDA pediatric label; hepatic dose reduction required at bilirubin >3× ULN.

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