Different genetic profiles contribute to worse overall survival in patients with leptomeningeal metastases of...

Area of Science:

• Oncology
• Genetics
• Neuro-oncology

Background:

• Central nervous system (CNS) metastases are a significant complication of non-small-cell lung cancer (NSCLC).
• Understanding the genetic landscape of brain metastases (BM) and leptomeningeal metastases (LM) is crucial for prognostic assessment.
• Identifying genetic drivers associated with survival is key for targeted therapies.

Purpose of the Study:

• To compare the genetic profiles of BM and LM in NSCLC patients.
• To identify specific genetic alterations correlating with overall survival (OS) in NSCLC patients with LM.
• To elucidate the genetic basis for differential outcomes between BM and LM.

Main Methods:

• 168-target panel sequencing was performed on 25 patients with BM and 52 patients with LM.
• Comprehensive genomic profiling was utilized to analyze mutation frequencies and patterns.
• Statistical analysis was employed to correlate genetic alterations with patient survival data.

Main Results:

• TP53 mutations were frequent in BM (44%), while EGFR mutations (77%) and amplifications (31%) were more prevalent in LM.
• Patients with LM showed significantly worse OS compared to those with BM (p=0.029).
• TP53, EGFR_amp, and CDKN2A mutations/deletions were associated with shorter OS in both BM and LM cohorts, particularly in LM.

Conclusions:

• Leptomeningeal metastases (LM) are associated with significantly poorer overall survival (OS) than brain metastases (BM) in NSCLC.
• Specific gene signatures, including TP53, EGFR_amp, and CDKN2A alterations, may contribute to the worse prognosis observed in LM patients.
• These findings highlight the importance of molecular profiling for understanding NSCLC CNS metastasis and guiding treatment strategies.