Adverse subtype or molecular feature in chondrosarcoma: dedifferentiated subtype (high-gr...

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

ID	`RF-CHONDROSARCOMA-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-26 \| pending_clinical_signoff
Diseases	`DIS-CHONDROSARCOMA`
Sources	`SRC-NCCN-NSCLC-2025` `SRC-ONCOKB`

Red Flag Origin

Definition	Adverse subtype or molecular feature in chondrosarcoma: dedifferentiated subtype (high-grade sarcoma component), mesenchymal subtype (HEY1-NCOA2 fusion, Ewing-like biology), grade III conventional histology, IDH1 R132 mutation in advanced unresectable disease (ivosidenib-eligible), or CDKN2A loss — each shifts treatment from observation/surgery alone to systemic therapy or trial enrollment.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "chondrosarcoma_subtype",
      "value": "dedifferentiated"
    },
    {
      "finding": "chondrosarcoma_subtype",
      "value": "mesenchymal"
    },
    {
      "finding": "chondrosarcoma_grade",
      "value": "III"
    },
    {
      "all_of": [
        {
          "finding": "BIO-IDH-MUTATION",
          "value": "positive"
        },
        {
          "finding": "unresectable_or_metastatic",
          "value": true
        }
      ]
    },
    {
      "finding": "BIO-CDKN2A",
      "value": "loss"
    }
  ],
  "type": "biomarker"
}

Notes

Chondrosarcoma decision-making is dominated by subtype + grade. Dedifferentiated (~10%) — biphasic with high-grade sarcoma component, behaves aggressively (5-yr OS ~30%) → doxorubicin + ifosfamide adjuvant by extrapolation from soft-tissue sarcoma protocols. Mesenchymal (~3–5%, young adults) — HEY1-NCOA2 fusion-positive small-round-blue-cell biology, treated like Ewing (VDC/IE protocols) — chemo-sensitive. Grade III conventional — consider adjuvant systemic therapy on trial. IDH1 R132 mutant (~40–50% of conventional) — ivosidenib has signal in advanced unresectable disease (Tap et al JCO 2020); off-label / trial. CDKN2A loss is prognostic in dedifferentiated subtype.

Used By

No reverse references found in the YAML corpus.