Age ≥75 with ECOG ≥2 or ≥2 comorbidities — doxorubicin + ifosfamide (AI) neoadjuvant poor...

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

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

Red Flag Origin

Definition	Age ≥75 with ECOG ≥2 or ≥2 comorbidities — doxorubicin + ifosfamide (AI) neoadjuvant poorly tolerated; consider doxorubicin monotherapy with cardio-protection, pazopanib monotherapy for advanced disease, hypofractionated RT alone, or surgical-margin-focused approach without systemic therapy.
Clinical direction	de-escalate
Category	frailty-age

Trigger Logic

{
  "all_of": [
    {
      "comparator": ">=",
      "finding": "age_years",
      "threshold": 75
    },
    {
      "any_of": [
        {
          "comparator": ">=",
          "finding": "ecog_status",
          "threshold": 2
        },
        {
          "comparator": ">=",
          "finding": "comorbidity_count",
          "threshold": 2
        }
      ]
    }
  ],
  "type": "composite_clinical"
}

Notes

AI is not well-tolerated in elderly: ifosfamide encephalopathy, cumulative thrombocytopenia, doxorubicin cardiotoxicity. Sarcoma trials (EORTC 62012) showed marginal AI benefit over doxorubicin monotherapy in advanced STS — this informs de-escalation rationale in elderly / frail. Pazopanib (PALETTE) reasonable second-line, less acute toxicity but cumulative fatigue + hypertension. Hypofractionated RT (54 Gy / 18 fractions) emerging as feasible for elderly with comorbidity- limited surgical candidacy. NF1-MPNST in elderly often presents with larger / more invasive primary — surgical complexity adds to fragility.

Used By

No reverse references found in the YAML corpus.