Baseline organ dysfunction precluding standard doxorubicin + ifosfamide (AI) neoadjuvant...

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

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

Red Flag Origin

Definition	Baseline organ dysfunction precluding standard doxorubicin + ifosfamide (AI) neoadjuvant or salvage chemotherapy in MPNST: LVEF <50% (anthracycline contraindicated), CrCl <30 mL/min (ifosfamide nephrotoxicity), bilirubin >3× ULN (doxorubicin / ifosfamide hepatic metabolism), or DLCO <60% (post-thoracotomy reserve concern for pulmonary metastasectomy candidacy).
Clinical direction	de-escalate
Category	organ-dysfunction

Trigger Logic

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

Notes

AI is the soft-tissue sarcoma standard for high-grade MPNST in the preoperative setting (EORTC 62931 / 62012 data extrapolation). LVEF <50: substitute liposomal doxorubicin or omit anthracycline (ifosfamide + epirubicin or pazopanib alternative for advanced). CrCl <30: ifosfamide contraindicated — switch to dose-modified doxorubicin monotherapy. Pazopanib (PALETTE in non-MPNST STS) has limited but documented activity in MPNST — used in cisplatin / ifosfamide- ineligible. NF1-MPNST patients often have additional comorbidity (cardiomyopathy, scoliosis) lowering tolerance. DLCO <60: limits metastasectomy candidacy.

Used By

No reverse references found in the YAML corpus.