Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR...

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

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

Red Flag Origin

Definition	Treatment-defining biomarkers in metastatic gastric/GEJ adenocarcinoma: HER2+ (IHC 3+ OR 2+/ISH+) → trastuzumab+chemo TOGA / T-DXd 2L+; CLDN18.2+ (≥75% of tumor cells with 2+ membranous staining) → zolbetuximab+chemo SPOTLIGHT/GLOW; MSI-H → pembrolizumab mono; EBV+ subtype (TCGA molecular class) — distinct biology, ICI-favorable.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-GASTRIC-METASTATIC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "her2_status",
      "value": "positive"
    },
    {
      "finding": "cldn18_2_status",
      "value": "positive"
    },
    {
      "finding": "msi_status",
      "value": "MSI-H"
    },
    {
      "finding": "ebv_status_tumor",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Sequential biomarker test cascade: HER2 IHC → ISH if 2+; PD-L1 CPS; MSI-H reflex; CLDN18.2 IHC. EBV by EBER-ISH if MSI-WT non-classic signet-ring. Multiple actionable biomarkers can co-exist (HER2+ MSI-H ~3% — ICI + trastuzumab combinations under study).

Used By

Algorithms

ALGO-GASTRIC-2L - ALGO-GASTRIC-2L
ALGO-GASTRIC-METASTATIC-1L - ALGO-GASTRIC-METASTATIC-1L