Salivary gland carcinoma with actionable molecular driver: ETV6-NTRK3 fusion (mammary ana...

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

ID	`RF-SALIVARY-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-SALIVARY`
Sources	`SRC-ESMO-SALIVARY` `SRC-ONCOKB`

Red Flag Origin

Definition	Salivary gland carcinoma with actionable molecular driver: ETV6-NTRK3 fusion (mammary analog secretory carcinoma — ~100% MASC, larotrectinib / entrectinib), HER2 amplification (salivary duct carcinoma ~30-40%, trastuzumab + chemotherapy), HRAS mutation (SDC ~10-15%, tipifarnib), PIK3CA mutation (SDC ~20-30%), AR positivity (~70-80% SDC, androgen deprivation), or NOTCH1 mutation (adenoid cystic ~15%, gamma-secretase inhibitors in trials) — re-routes from cytotoxic chemotherapy to histology-specific targeted therapy.
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-NTRK-FUSION",
      "value": "positive"
    },
    {
      "finding": "BIO-HER2-SOLID",
      "value": "positive"
    },
    {
      "finding": "BIO-HRAS",
      "value": "positive"
    },
    {
      "finding": "BIO-PIK3CA-MUTATION",
      "value": "positive"
    },
    {
      "finding": "BIO-NOTCH1-MUTATION",
      "value": "positive"
    },
    {
      "finding": "androgen_receptor_status",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Salivary gland carcinoma is a histology-defined umbrella with distinct molecular drivers: MASC ~100% ETV6-NTRK3 fusion → larotrectinib (ORR ~80% basket trials). Salivary duct carcinoma (SDC) ~70-80% AR+ → bicalutamide + LHRH analog (EORTC-1206 phase 2 confirms benefit); ~30-40% HER2+ → trastuzumab + paclitaxel (similar ORR to breast cancer trials); HRAS-mutant ~10-15% → tipifarnib (KO-TIP-007 ORR ~38% in HRAS-mutant SDC). Adenoid cystic carcinoma ~15% NOTCH1 mutant — AL101 / brontictuzumab in trials; otherwise cisplatin-based chemo modest activity. Comprehensive histology + molecular profiling at diagnosis is now ESMO-recommended for advanced salivary cancer.

Used By

No reverse references found in the YAML corpus.