Actionable molecular biology in PDAC: germline BRCA1/2 (or PALB2 — HRD-equivalent → olapa...

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

ID	`RF-PDAC-HIGH-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-04-26 \| pending_clinical_signoff
Diseases	`DIS-PDAC`
Sources	`SRC-ESMO-PANCREATIC-2024` `SRC-NCCN-PANCREATIC-2025`

Red Flag Origin

Definition	Actionable molecular biology in PDAC: germline BRCA1/2 (or PALB2 — HRD-equivalent → olaparib POLO maintenance after platinum response); MSI-H / dMMR (~1% of PDAC — pembrolizumab pan-cancer indication); KRAS G12C (~1-2% — sotorasib / adagrasib + cetuximab combinations emerging); NRG1-fusion (rare — zenocutuzumab).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-PDAC-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "brca1_brca2_germline_pathogenic",
      "value": true
    },
    {
      "finding": "palb2_germline_pathogenic",
      "value": true
    },
    {
      "finding": "msi_status",
      "value": "MSI-H"
    },
    {
      "finding": "kras_g12c",
      "value": true
    },
    {
      "finding": "nrg1_fusion",
      "value": true
    }
  ],
  "type": "biomarker"
}

Notes

Germline NGS (24-gene HBOC + Lynch panel) + tumor NGS recommended for ALL PDAC at diagnosis (NCCN MS-12). POLO trial: olaparib maintenance after ≥16 weeks platinum without progression in BRCA1/2-germline mPDAC — mPFS 7.4 vs 3.8 mo placebo.

Used By

Algorithms

ALGO-PDAC-METASTATIC-1L - ALGO-PDAC-METASTATIC-1L