ROS1 fusion (CD74-ROS1, EZR-ROS1, others) — ~1-2% of NSCLC adenocarcinoma; never-smoker e...

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

ID	`RF-NSCLC-ROS1-FUSION-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025` `SRC-STARTRK2-DRILON-2020` `SRC-TRIDENT1-DRILON-2024`

Red Flag Origin

Definition	ROS1 fusion (CD74-ROS1, EZR-ROS1, others) — ~1-2% of NSCLC adenocarcinoma; never-smoker enriched. Treatment-defining: entrectinib (CNS-active) or repotrectinib (TRIDENT-1, including post-crizotinib resistance) preferred 1L; crizotinib historic option.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-1L, ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "ros1_fusion",
      "value": true
    },
    {
      "finding": "ros1_rearrangement",
      "value": "positive"
    },
    {
      "finding": "ros1_status",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Detection: RNA-NGS preferred for fusion partner; IHC screen with ROS1 antibody (D4D6) acceptable. Repotrectinib next-gen TKI active vs solvent-front G2032R resistance mutation; preferred 1L+ in guidelines updated post-TRIDENT-1. Brain metastases — entrectinib and repotrectinib have CNS activity; crizotinib does not.

Used By

Algorithms

ALGO-NSCLC-METASTATIC-1L - ALGO-NSCLC-METASTATIC-1L
ALGO-NSCLC-METASTATIC-2L - ALGO-NSCLC-METASTATIC-2L