Genomic alterations and the incidence of brain metastases in advanced and metastatic non-small cell lung cancer: a systematic review and meta-analysis.

Gillespie, Conor S, Mustafa, Mohammad A, Richardson, George E, Alam, Ali M ORCID: 0000-0001-6014-3263, Lee, Keng Siang, Hughes, David M ORCID: 0000-0002-1287-9994, Escriu, Carles ORCID: 0000-0003-3638-3202 and Zakaria, Rasheed ORCID: 0000-0001-6826-2662 (2023) Genomic alterations and the incidence of brain metastases in advanced and metastatic non-small cell lung cancer: a systematic review and meta-analysis. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 18 (12). S1556-0864(23)00638-X-S1556-0864(23)00638-X.

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Official URL: http://dx.doi.org/10.1016/j.jtho.2023.06.017

Abstract

<h4>Background</h4>Brain metastases (BM) in patients with advanced and metastatic non-small cell lung cancer (NSCLC) are linked with 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.<h4>Patients and methods</h4>A PRISMA-compliant systematic review and meta-analysis was conducted (PROSPERO ID CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000-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.<h4>Results</h4>Sixty-four unique articles were included (24,784 NSCLC patients with prevalence data from forty-five studies and 9,058 NSCLC patients with incidence data from forty 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, 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 (5 studies, 95% CI 0.10-0.27), 0.10 in the KRAS group (4 studies, 95% CI 0.06-0.17), 0.13 in the ROS1 group (3 studies, 95% CI 0.06-0.28), and 0.12 in the RET group (2 studies, 95% CI 0.08-0.17).<h4>Conclusions</h4>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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Carcinoma, Non-Small-Cell Lung, Brain Neoplasms, Lung Neoplasms, Receptor Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Incidence, Genomics, Proto-Oncogene Proteins p21(ras), Protein-Tyrosine Kinases, ErbB Receptors
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	06 Jul 2023 07:11
Last Modified:	06 Dec 2023 16:32
DOI:	10.1016/j.jtho.2023.06.017
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3171448