Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Nov 7:15:1493773.
doi: 10.3389/fimmu.2024.1493773. eCollection 2024.

Impact of bone metastasis on prognosis in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Yonghua Zhu #  1 , Jingyao She #  2 , Rong Sun #  3 , XinXin Yan #  4 , Xinyao Huang  1 , Peijuan Wang  2 , Bo Li  5 , Xiangdong Sun  3 , Changqing Wang  1 , Kai Jiang  3
Affiliations
Meta-Analysis

Impact of bone metastasis on prognosis in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Yonghua Zhu et al. Front Immunol. .

Abstract

Background: Lung cancer is a leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. While immune checkpoint inhibitors (ICIs) have transformed treatment for advanced NSCLC, the role of bone metastasis in modulating ICI efficacy remains unclear. Bone metastasis, occurring in 30-40% of advanced NSCLC cases, is associated with worse outcomes. However, how this affects the therapeutic benefit of ICIs has not been fully elucidated, highlighting a critical knowledge gap in optimizing treatment for this patient population.

Methods: A comprehensive literature search across multiple databases, including PubMed, Embase, and Cochrane, identified 13 studies with a total of 3,681 patients, of whom 37.6% had bone metastasis. Overall survival (OS) and progression-free survival (PFS) were compared between NSCLC patients with and without bone metastasis. Data were analyzed using a random-effects model to account for study heterogeneity.

Results: The meta-analysis demonstrated that bone metastasis significantly worsened overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs. Specifically, bone metastasis was associated with a 45% increased risk of death (HR: 1.45, 95% CI: 1.30-1.62, p < 0.001) and a 40% increased risk of disease progression (HR: 1.40, 95% CI: 1.25-1.58, p < 0.001). No statistically significant impact on PFS was observed. (HR: 1.28, 95% CI: 0.77-2.10, p = 0.34). High heterogeneity was observed in some subgroup analyses (I² = 72%), indicating variability in the results.

Conclusion: Bone metastasis is a significant negative prognostic factor for NSCLC patients treated with ICIs, associated with a higher risk of mortality and disease progression. These results underscore the importance of tailored treatment approaches for NSCLC patients with bone metastasis and call for further research to optimize therapy outcomes in this group.

Keywords: bone metastasis; immune checkpoint inhibitors; meta-analysis; non-small cell lung cancer; prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
study selection flow chart.
Figure 2
Figure 2
Risk of bias assessment. (A) Risk of bias summary for all included studies. (B) Risk of bias assessment for individual studies.
Figure 3
Figure 3
Meta-analysis of the effect of none metastasis on overall survival in NSCLC patients receiving immune checkpoint inhibitors.
Figure 4
Figure 4
Meta-analysis of the effect of none metastasis on overall survival in NSCLC patients receiving immune checkpoint inhibitors.
Figure 5
Figure 5
Subgroup Meta-analysis of the impact of bone metastasis on OS in NSCLC patients treated with ICIs Forest plot.
Figure 6
Figure 6
Subgroup Meta-analysis of the impact of bone metastasis on OS in NSCLC patients treated with ICIs Funnel plot.
Figure 7
Figure 7
Sensitivity analysis of bone metastasis on OS in NSCLC patients treated with ICIs.
Figure 8
Figure 8
Meta-analysis of the effect of bone metastasis on progression-free survival in NSCLC patients treated with immune checkpoint inhibitors.
Figure 9
Figure 9
Publication bias of the effect of bone metastasis on progression-free survival in NSCLC patients treated with immune checkpoint inhibitors.
See this image and copyright information in PMC

References

    1. Wang K, Gu Y, Liao Y, Bang S, Donnelly CR, Chen O, et al. . PD-1 blockade inhibits osteoclast formation and murine bone cancer pain. J Clin Invest. (2020) 130:3603–20. doi: 10.1172/JCI133334 - DOI - PMC - PubMed
    1. Zhou J, Lu X, Zhu H, Ding N, Zhang Y, Xu X, et al. . Resistance to immune checkpoint inhibitors in advanced lung cancer: Clinical characteristics, potential prognostic factors and next strategy. Front Immunol. (2023) 14:1089026. doi: 10.3389/fimmu.2023.1089026 - DOI - PMC - PubMed
    1. Del Conte A, De Carlo E, Bertoli E, Stanzione B, Revelant A, Bertola M, et al. . Bone metastasis and immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): microenvironment and possible clinical implications. Int J Mol Sci. (2022) 23:6832. doi: 10.3390/ijms23126832 - DOI - PMC - PubMed
    1. Zhu YJ, Chang XS, Zhou R, Chen YD, Ma HC, Xiao ZZ, et al. . Bone metastasis attenuates efficacy of immune checkpoint inhibitors and displays “cold” immune characteristics in Non-small cell lung cancer. Lung Cancer. (2022) 166:189–96. doi: 10.1016/j.lungcan.2022.03.006 - DOI - PubMed
    1. Xie X, Zhou M, Wang L, Wang F, Deng H, Yang Y, et al. . Effects of combining immune checkpoint inhibitors and anti-angiogenic agents on bone metastasis in non-small cell lung cancer patients. Hum Vaccin Immunother. (2023) 19:2241310. doi: 10.1080/21645515.2023.2241310 - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources