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Background <p>Central nervous system (CNS) metastasis is common in patients with non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Evidence guiding optimal clinical management remains limited, and comprehensive studies on animal models that recapitulate different CNS metastatic patterns are lacking.</p> Methods <p>A total of 316 NSCLC patients with CNS metastases were retrospectively enrolled between May 2019 and February 2024. Patients were categorized into four groups: brain metastases only (BM, n = 145), leptomeningeal metastases only (LM, n = 43), concurrent brain and leptomeningeal metastases (BM+LM, n = 62), and brain metastases preceding leptomeningeal metastases (BM–LM, n = 66). Overall survival was analyzed using survival curves. To explore the distinct biological processes underlying BM and LM, mouse models of brain metastasis were established using tail vein, internal carotid artery, and left ventricular injection methods.</p> Results <p>Survival analysis demonstrated that patients with LM had significantly shorter overall survival compared with those with BM alone (<i>P</i> &lt; 0.05). Patients with concurrent BM and LM also exhibited poorer overall survival than those in whom BM preceded LM (<i>P</i> &lt; 0.01). In animal experiments, brain metastasis developed in one of five mice following tail vein injection, one of five following internal carotid artery injection, and two of five following left ventricular injection, indicating the highest success rate with the latter approach. None of the animal models successfully reproduced the sequential progression from brain metastasis to leptomeningeal metastasis.</p> Conclusion <p>Leptomeningeal involvement in NSCLC is associated with significantly worse survival outcomes compared with brain metastasis alone. Although several injection strategies can generate brain metastasis in mice, current models fail to simulate the transition from brain metastasis to leptomeningeal metastasis, highlighting the need for improved and more representative animal models.</p>

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Survival of lung cancer patients with central nervous system metastases: from clinical trials to mouse models

  • 期刊论文

  • 发表日期：

    2026年1月23日

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  • Hainan Yang,
  • Chengji Wang,
  • Hui Ye,
  • Tao Lin,
  • Weifang Yuan,
  • Changguo Shan,
  • Qingjun Hu,
  • Xin Jin,
  • Da Liu,
  • Lei Wen,
  • Ming Lei

摘要

Background

Central nervous system (CNS) metastasis is common in patients with non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Evidence guiding optimal clinical management remains limited, and comprehensive studies on animal models that recapitulate different CNS metastatic patterns are lacking.

Methods

A total of 316 NSCLC patients with CNS metastases were retrospectively enrolled between May 2019 and February 2024. Patients were categorized into four groups: brain metastases only (BM, n = 145), leptomeningeal metastases only (LM, n = 43), concurrent brain and leptomeningeal metastases (BM+LM, n = 62), and brain metastases preceding leptomeningeal metastases (BM–LM, n = 66). Overall survival was analyzed using survival curves. To explore the distinct biological processes underlying BM and LM, mouse models of brain metastasis were established using tail vein, internal carotid artery, and left ventricular injection methods.

Results

Survival analysis demonstrated that patients with LM had significantly shorter overall survival compared with those with BM alone (P < 0.05). Patients with concurrent BM and LM also exhibited poorer overall survival than those in whom BM preceded LM (P < 0.01). In animal experiments, brain metastasis developed in one of five mice following tail vein injection, one of five following internal carotid artery injection, and two of five following left ventricular injection, indicating the highest success rate with the latter approach. None of the animal models successfully reproduced the sequential progression from brain metastasis to leptomeningeal metastasis.

Conclusion

Leptomeningeal involvement in NSCLC is associated with significantly worse survival outcomes compared with brain metastasis alone. Although several injection strategies can generate brain metastasis in mice, current models fail to simulate the transition from brain metastasis to leptomeningeal metastasis, highlighting the need for improved and more representative animal models.