Non-Small Cell Lung Cancer Brain Metastasis (MSK, Nat Commun 2023)

Overview

MSK cohort of resected NSCLC brain metastases (BM) profiled with MSK-IMPACT alongside matched primary tumors and extracranial metastases, used to characterize the genomic correlates of BM development and patterns of intracranial progression PMID:37591896.

Composition

  • 233 patients with resected NSCLC BM: 180 (77%) LUAD, 23 (10%) LUSC, 30 (13%) other NSCLC; median age 67; 57% female; 80% current/former smokers PMID:37591896.
  • Matched samples: 47 primary tumors and 42 extracranial metastases; LUAD-restricted downstream analyses used 179 BM, 37 PT, 34 EM PMID:37591896.

Assays / panels (linked)

Papers using this cohort

  • PMID:37591896 — Skakodub et al., genomic analysis and clinical correlations of NSCLC brain metastasis.

Notable findings derived from this cohort

  • BM samples had higher TMB (median 8.8 vs 5.8; p=0.00766) and higher FGA than extracranial metastases and primary tumors PMID:37591896.
  • CDKN2A/CDKN2B deep deletions and broader cell-cycle pathway alterations were enriched in BM vs PT (34% vs 13%, p=0.003, q=0.04) PMID:37591896.
  • Patients who developed leptomeningeal disease had more EGFR alterations (45% vs 21%; p=0.044), frequently non-canonical drivers (L861Q, G719A/S, A755G, N771_H773dup) PMID:37591896.
  • MYC amplifications associated with multifocal regional intracranial progression (22% vs 0% in local progressors; p=0.023) PMID:37591896.

Sources

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