EGFR 突变型 NSCLC 脑膜转移个体化管理风险分层模型的开发与验证 (LM-Index)

Development and validation of a risk-stratification model for individualized management of leptomeningeal metastases in EGFR- mutant NSCLC (LM-Index).

期刊: Lung Cancer
PMID: 42501706
原文: PubMed ↗
发布日期: 2026-07-26

作者

Yingxi Wu — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Haiyang Chen — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Yufeng Wu — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Qi Zhao — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Xuan Wu — Department of Medical Oncology, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou, China.
Yuhua Zhao — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Lanwei Guo — Department of Clinical Research Management, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.
Huiying Li — Department of Geriatric Oncology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Wanwan Cheng — Department of Respiratory Medicine, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; Brain Metastases Diagnosis and Treatment Centre, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Longfeng Zhang — Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Weiran Xu — Comprehensive Oncology Center, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
Lili Wang — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Zhen He — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Sen Yang — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Cuicui Zhang — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Shuxiang Ma — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Peng Li — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Xiaoyan Li — Comprehensive Oncology Center, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
Haipeng Xu — Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Shencun Fang — Department of Respiratory Medicine, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; Brain Metastases Diagnosis and Treatment Centre, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Zhenyu Yin — Department of Geriatric Oncology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Qiming Wang — Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China. Electronic address: qimingwang1006@126.com.

作者单位

Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China.
Department of Medical Oncology, Henan Provincial Chest Hospital, Chest Hospital of Zhengzhou University, Zhengzhou, China.
Department of Clinical Research Management, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.
Department of Geriatric Oncology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Respiratory Medicine, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China; Brain Metastases Diagnosis and Treatment Centre, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Comprehensive Oncology Center, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China.
Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China; State Key Laboratory of Neurology and Oncology Drug Development, China; Henan International Joint Laboratory of Drug Resistance and Reversal of Targeted Therapy for Lung Cancer, China; Henan Medical Key Laboratory of Refractory Lung Cancer, China; Henan Province Engineering Technology Research Center of Refractory Lung Cancer Drug Treatment, China. Electronic address: qimingwang1006@126.com.

摘要

中文

携带 EGFR 突变的非小细胞肺癌合并脑膜转移患者预后高度不确定,使治疗决策复杂化。本研究旨在开发并验证一种多模态风险评分,以预测总生存期 (OS) 并实现风险分层管理。本回顾性多中心研究包括推导队列 (n=350) 与独立外部验证队列 (n=302)。通过 Cox 回归筛选独立预后因素,并整合为基于整数计分的风险评分。模型性能通过 C-index、校准度及决策曲线分析进行评估。多因素分析确定 5 个较差 OS 的独立预测因素:ECOG PS ≥3、脑转移、MRI 上脑膜强化、脑脊液细胞学 (CSFC) 阳性及颅内压 >220 mmH₂O。由此构建的风险评分将患者分为低危组和高危组,中位 OS 分别为 22.6 个月和 9.9 个月 (p<0.001)。模型表现出良好的区分度,偏差校正 C-index 为 0.73。在外部验证队列中,所有因素仍具有显著性,模型性能保持一致 (C-index=0.71)。模型显示出良好的校准度和正向净获益。我们开发并验证了一种稳健、临床可行的风险评分,能够准确分层 EGFR 突变型 NSCLC 合并 LM 患者的 OS。该实用工具可促进风险分层患者咨询,并可能有助于未来临床试验设计。

English

Prognosis for patients with EGFR- mutant non-small-cell lung cancer and leptomeningeal metastasis is highly uncertain, complicating treatment decisions. We aimed to develop and validate a multimodal risk score for predicting overall survival to enable risk-stratified management. In this retrospective, multicenter study, a derivation cohort (n = 350) and an independent external validation cohort (n = 302) were used. Independent prognostic factors were identified via Cox regression and integrated into an integer-based risk score. Model performance was evaluated by the C-index, calibration, and decision curve analysis. Multivariate analysis identified five independent predictors of poorer OS: ECOG PS ≥ 3, brain metastasis, meningeal enhancement on MRI, positive Cerebrospinal Fluid cytology (CSFC) and intracranial pressure > 220 mmH2O. The resulting risk score stratified patients into low-risk and high-risk groups, with median OS of 22.6 months versus 9.9 months, respectively (p < 0.001). The model demonstrated good discrimination, with a bias-corrected C-index of 0.73. In the external validation cohort, all factors remained significant, and the model maintained consistent performance (C-index = 0.71). The model showed good calibration and positive net benefit. We developed and validated a robust, clinically accessible risk score that accurately stratifies OS in patients with EGFR- mutant NSCLC and LM. This practical tool facilitates risk‑stratified patient counseling and may aid in the design of future clinical trials.

分类与指标

研究类型: 临床研究
病种: 肺癌
JCR 分区: Q1
影响因子: 5.3
新锐分区: 2区