Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Hu, Hao; Xu, Zhiyong; Zhu, Qian; Liu, Xi; Jiang, Si‐Cong; Zheng, Jihua

doi:10.3389/fimmu.2021.669398

Cited by 11 publications

(7 citation statements)

References 58 publications

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“…Given the paucity of effective treatment for BrMs, it is important to identify promising new targets for therapeutic intervention. Recent clinical trials have shown that ICB-based immunotherapies may benefit lung cancer patients with or without brain metastasis 2 , 4 , 5 . However, not all patients respond to immunotherapies, and effective biomarkers are needed to identify those that would most likely benefit from the treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, once cancer has spread to the brain, a frequent event in late-stage lung cancer, treatment options are limited. Although antibodies blocking the programed death 1/ligand 1 (PD-1/L1) and inhibitors targeting the disease-driving tyrosine kinases have shown clinical benefits for cancer patients with brain metastasis 2 – 7 , the median 5-year survival rate for the BrM patients is <5% 8 . Given the prevalence of BrMs and the associated high morbidity and high mortality, there is an urgent need to identify prognostic biomarkers for patient stratification, therapeutic targets for intervention, and genomic and transcriptomic correlates of therapeutic response.…”

Section: Introductionmentioning

confidence: 99%

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The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

et al. 2022

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Brain metastases (BrMs) are a common occurrence in lung cancer with a dismal outcome. To understand the mechanism of metastasis to inform prognosis and treatment, here we analyze primary and metastasized tumor specimens from 44 non-small cell lung cancer patients by spatial RNA sequencing, affording a whole transcriptome map of metastasis resolved with morphological markers for the tumor core, tumor immune microenvironment (TIME), and tumor brain microenvironment (TBME). Our data indicate that the tumor microenvironment (TME) in the brain, including the TIME and TBME, undergoes extensive remodeling to create an immunosuppressive and fibrogenic niche for the BrMs. Specifically, the brain TME is characterized with reduced antigen presentation and B/T cell function, increased neutrophils and M2-type macrophages, immature microglia, and reactive astrocytes. Differential gene expression and network analysis identify fibrosis and immune regulation as the major functional modules disrupted in both the lung and brain TME. Besides providing systems-level insights into the mechanism of lung cancer brain metastasis, our study uncovers potential prognostic biomarkers and suggests that therapeutic strategies should be tailored to the immune and fibrosis status of the BrMs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

et al. 2022

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“…This approach has been used in previous studies ( 19 ). To avoid the risk of ecological bias for RCTs, an interaction trial-specific HR ratio (ratio of the HR in patients with liver metastases to the HR in patients without liver metastases) was calculated for each RCT, and the trial-specific HR ratios were then pooled using the deft approach ( 20 ), the feasibility of which has been confirmed by previous studies ( 21 , 22 ). In order to make the analysis more accurate, this meta-analysis was performed separately for patients with NSCLC and small cell lung cancer (SCLC).…”

Section: Methodsmentioning

confidence: 99%

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Xia

Zhang²,

Zhang³

et al. 2022

Front. Oncol.

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BackgroundLiver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies.MethodsPubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle–Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach.ResultsA total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61–0.97; OS HR, 0.78; 95%CI, 0.68–0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS–HRs, 1.19; 95%CI, 1.02–1.39; P=0.029; Ratios of OS–HRs, 1.10; 95%CI, 0.94–1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73–1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS–HRs, 1.22; 95%CI, 1.01–1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17–1.27; P<0.0001). Subgroup analysis confirmed that this association was not modified by race (Asian vs. Western) or number of treatment lines.ConclusionsThe presence of liver metastases does not significantly influence the OS benefit of ICIs in patients with NSCLC. However, a small amount of data shows that liver metastasis restrains the magnitude of OS benefit in patients with SCLC. Liver metastasis has potential as an independent prognostic risk factor for lung cancer patients receiving ICI treatment in clinical practice.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022306449).

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“… 61 Nevertheless, several clinical trials have revealed that BM status does not significantly influence the efficacy of immunotherapy in lung cancer, suggesting both BM and non-BM patients could obtain comparable benefits. 62 Hence, further studies on the influence of the BM molecular background on the efficacy of immunotherapy in patients with NSCLC are necessary.…”

Section: Discussionmentioning

confidence: 99%

Genomic Profiling Identifies Putative Pathogenic Alterations in NSCLC Brain Metastases

Nicoś

Harbers

Patrucco

et al. 2022

JTO Clinical and Research Reports

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Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Cited by 11 publications

References 58 publications

The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis

Genomic Profiling Identifies Putative Pathogenic Alterations in NSCLC Brain Metastases

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