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Purpose <p>Leptomeningeal metastasis (LM) carries a poor prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore clinical features and survival outcomes and develop a nomogram for overall survival (OS) in this population.</p> Methods <p>We retrospectively enrolled 288 EGFR-mutant NSCLC patients with LM from Fujian Cancer Hospital (January 2019–March 2024). Prognostic variables were selected by LASSO regression followed by multivariable Cox proportional hazards modeling. Internal validation used 1000-iteration bootstrap resampling. Model performance was assessed by the time-dependent area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis.</p> Results <p>Median OS was 16.2 months. Before LM, 71.5% of patients received third-generation EGFR tyrosine kinase inhibitors (TKIs), and 76.7% received third-generation EGFR-TKI therapy after LM. Eight variables were identified by LASSO-Cox regression: ECOG performance status (PS), prior lines of systemic therapy, cranial MRI findings, third-generation EGFR-TKI therapy before and after LM, antiangiogenic therapy after LM, chemotherapy after LM, and CNS radiotherapy after LM. Post-LM third-generation EGFR-TKI therapy was the strongest treatment-associated prognostic factor (HR = 2.23; <i>p</i> &lt; 0.001), with survival benefit maintained regardless of prior third-generation EGFR-TKI exposure (prior-exposed: HR = 0.60, <i>p</i> = 0.029; TKI-naïve: HR = 0.18, <i>p</i> &lt; 0.001). The nomogram demonstrated good discrimination (AUC: 0.777, 0.778, and 0.742 for 6-, 12-, and 18-month OS; C-index: 0.716).</p> Conclusion <p>In EGFR-mutant NSCLC patients with LM, post-LM third-generation EGFR-TKI therapy was associated with longer survival, regardless of prior third-generation EGFR-TKI use. The nomogram may support individualized risk stratification but requires external validation in independent multi-institutional cohorts.</p>

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Survival outcomes and a prognostic nomogram in EGFR-mutant non-small cell lung cancer with leptomeningeal metastasis: a real-world cohort study

  • 期刊论文

  • 发表日期：

    2026年6月26日

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  • Yaping Hong,
  • Rongqi Jiang,
  • Shijie Chen,
  • Dongzhu Lu,
  • Jinlan Lin,
  • Pan Huang,
  • Jingyi Qu,
  • Junfei Deng,
  • Jingqi He,
  • Yunjian Huang,
  • Jinhuo Lai

摘要

Purpose

Leptomeningeal metastasis (LM) carries a poor prognosis in EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore clinical features and survival outcomes and develop a nomogram for overall survival (OS) in this population.

Methods

We retrospectively enrolled 288 EGFR-mutant NSCLC patients with LM from Fujian Cancer Hospital (January 2019–March 2024). Prognostic variables were selected by LASSO regression followed by multivariable Cox proportional hazards modeling. Internal validation used 1000-iteration bootstrap resampling. Model performance was assessed by the time-dependent area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis.

Results

Median OS was 16.2 months. Before LM, 71.5% of patients received third-generation EGFR tyrosine kinase inhibitors (TKIs), and 76.7% received third-generation EGFR-TKI therapy after LM. Eight variables were identified by LASSO-Cox regression: ECOG performance status (PS), prior lines of systemic therapy, cranial MRI findings, third-generation EGFR-TKI therapy before and after LM, antiangiogenic therapy after LM, chemotherapy after LM, and CNS radiotherapy after LM. Post-LM third-generation EGFR-TKI therapy was the strongest treatment-associated prognostic factor (HR = 2.23; p < 0.001), with survival benefit maintained regardless of prior third-generation EGFR-TKI exposure (prior-exposed: HR = 0.60, p = 0.029; TKI-naïve: HR = 0.18, p < 0.001). The nomogram demonstrated good discrimination (AUC: 0.777, 0.778, and 0.742 for 6-, 12-, and 18-month OS; C-index: 0.716).

Conclusion

In EGFR-mutant NSCLC patients with LM, post-LM third-generation EGFR-TKI therapy was associated with longer survival, regardless of prior third-generation EGFR-TKI use. The nomogram may support individualized risk stratification but requires external validation in independent multi-institutional cohorts.