Actionable molecular alteration in cholangiocarcinoma — FGFR2 fusion / rearrangement, IDH...

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

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

Red Flag Origin

Definition	Actionable molecular alteration in cholangiocarcinoma — FGFR2 fusion / rearrangement, IDH1 R132 mutation, BRAF V600E, HER2 amplification, NTRK fusion, MSI-high / dMMR, or BRCA1/2 mutation — opens a targeted-therapy line distinct from gem-cis-durvalumab and is decisive at progression.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-FGFR2-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-IDH1-MUTATION",
      "value": "positive"
    },
    {
      "finding": "BIO-BRAF-V600E",
      "value": "positive"
    },
    {
      "finding": "BIO-HER2-SOLID",
      "value": "positive"
    },
    {
      "finding": "BIO-NTRK-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-MSI",
      "value": "high"
    },
    {
      "finding": "BIO-BRCA-GERMLINE",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Intrahepatic cholangiocarcinoma is the most molecularly fertile of GI tumors: FGFR2 fusions (~10–15% iCCA) — pemigatinib (FIGHT-202), futibatinib (FOENIX-CCA2), infigratinib; IDH1 R132 (~15% iCCA) — ivosidenib (ClarIDHy); BRAF V600E (~5%) — dabrafenib + trametinib (ROAR basket); HER2 amp (~5–15% extrahepatic / GBC) — trastuzumab + pertuzumab (MyPathway), zanidatamab (HERIZON-BTC-01); NTRK fusion (<1%) — larotrectinib / entrectinib; MSI-H (~1%) — pembrolizumab (KEYNOTE-158); BRCA — olaparib data emerging. Comprehensive genomic profiling at diagnosis is now standard for advanced biliary cancer (NCCN Cat 1 recommendation level for iCCA). Each positive biomarker re-routes the Algorithm.

Used By

No reverse references found in the YAML corpus.