Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis

J Thorac Oncol. 2023 Dec;18(12):1703-1713. doi: 10.1016/j.jtho.2023.06.017. Epub 2023 Jun 29.


Introduction: Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.

Methods: A systematic review and meta-analysis compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were conducted (PROSPERO identification CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000 and May 2022 were included. Prevalence at diagnosis and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.

Results: A total of 64 unique articles were included (24,784 patients with NSCLC with prevalence data from 45 studies and 9058 patients with NSCLC having incidence data from 40 studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% confidence interval [CI]: 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, the per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI: 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI: 0.11-0.21), 0.17 in the ALK group (five studies, 95% CI: 0.10-0.27), 0.10 in the KRAS group (four studies, 95% CI: 0.06-0.17), 0.13 in the ROS1 group (three studies, 95% CI: 0.06-0.28), and 0.12 in the RET group (two studies, 95% CI: 0.08-0.17).

Conclusions: Comprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance.

Keywords: Brain metastases; Genomic; Incidence; Lung cancer; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / epidemiology
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Carcinoma, Non-Small-Cell Lung* / epidemiology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors / genetics
  • Genomics
  • Humans
  • Incidence
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / genetics


  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • ErbB Receptors