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Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.

ABSTRACT: Brain metastases stemming from lung cancer represent a common and challenging complication that significantly impacts patients' overall health. The migration of these cancerous cells from lung lesions to the central nervous system is facilitated by diverse molecular changes and a specific environment that supports their affinity for neural tissues. The advent of immunotherapy and its varied combinations in non-small cell lung cancer has notably improved patient survival rates, even in cases involving brain metastases. These therapies exhibit enhanced penetration into the central nervous system compared to traditional chemotherapy. This review outlines the molecular mechanisms underlying the development of brain metastases in lung cancer and explores the efficacy of novel immunotherapy approaches and their combinations.

SUBMITTER: Sereno M

PROVIDER: S-EPMC10811213 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.

Sereno Maria M Hernandez de Córdoba Irene I Gutiérrez-Gutiérrez Gerardo G Casado Enrique E

Frontiers in immunology 20240112

Brain metastases stemming from lung cancer represent a common and challenging complication that significantly impacts patients' overall health. The migration of these cancerous cells from lung lesions to the central nervous system is facilitated by diverse molecular changes and a specific environment that supports their affinity for neural tissues. The advent of immunotherapy and its varied combinations in non-small cell lung cancer has notably improved patient survival rates, even in cases invo ...[more]

PMID: 38283359

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Project description:BackgroundBrain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.MethodsElectronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.ResultsFourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58-0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52-0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71-0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56-0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78-1.18; P = 0.72) and 0.97 (95% CI, 0.79-1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.ConclusionWe demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

Dataset Information

Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.

Publications

Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.

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