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

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-IMT-ORGAN-DYSFUNCTION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-IMT`
Sources	`SRC-NCCN-SARCOMA` `SRC-ONCOKB`

Red Flag Origin

Definition	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).
Clinical direction	de-escalate
Category	organ-dysfunction

Trigger Logic

{
  "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"
}

Notes

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.

Used By

No reverse references found in the YAML corpus.