---
title: "Delayed Onset of Lung Cancer Leptomeningeal Metastasis and Era-Linked Post‑LM Survival in a 14‑Yea"
id: "pubmed-42670654"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42670654"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42670654/"
doi: "10.1111/1759-7714.70386"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Delayed Onset of Lung Cancer Leptomeningeal Metastasis and Era-Linked Post‑LM Survival in a 14‑Yea
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42670654
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42670654/)
- **DOI:** [10.1111/1759-7714.70386](https://doi.org/10.1111%2F1759-7714.70386)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This single-center retrospective cohort included 201 patients with cytologically confirmed **leptomeningeal metastasis (LM)** from lung cancer diagnosed between November 2012 and May 2026. - Patients were divided into two diagnostic eras: 2012–2016 and 2017–2026 to assess era-associated changes in LM timing and survival. - The later era (2017–2026) showed significantly longer intervals from initial lung cancer diagnosis and from Stage IV diagnosis to LM compared with the earlier era (23.7 vs. 13.8 months, p < 0.001; 17.4 vs. 10.4 months, p = 0.002). - Histology was dominated by **adenocarcinoma** (93.0% of cases). - Paired tissue and cerebrospinal fluid (CSF) molecular profiling was performed in 80 patients; **tissue–CSF driver discordance** was observed in 7 of 80 patients (8.75%), indicating CSF may reveal actionable differences. - Unadjusted overall survival (OS) after LM diagnosis did not differ significantly between eras (9.8 vs. 11.3 months, p = 0.864). - In multivariable Cox analysis, later diagnostic era, smoking, and ECOG performance status ≥2 were independently associated with higher post‑LM mortality (adjusted HRs 1.826, 1.847, and 1.674 respectively; p-values 0.014, 0.014, and 0.007). - Exposure to third‑generation **EGFR‑TKI** after LM diagnosis was associated with lower mortality (adjusted HR 0.385; p < 0.001). - Authors note adjusted associations should be interpreted cautiously because of potential residual confounding and post‑baseline treatment bias. - The study supports use of **CSF profiling** as a complementary source to primary tumor genotyping in LM management and highlights changing clinical timelines in the targeted‑therapy era.
## Clinical Analysis & Structured Key Points
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Delayed Occurrence of Lung Cancer Leptomeningeal Metastasis and Era-Associated Post-LM Survival: A 14-Year Single-Center Cohort Study [Xiaoxing Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Jie Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+J&cauthor_id=42670654)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-2 "Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Qiuyue Ye](https://pubmed.ncbi.nlm.nih.gov/?term=Ye+Q&cauthor_id=42670654)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-3 "Department of International Medical Service, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Chen Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+C&cauthor_id=42670654)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-4 "Center for Health Policy and Health Economics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China."), [Qing Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Q&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Xiaoyan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Minjiang Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+M&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Jing Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+J&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Hanping Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Xiaoyan Si](https://pubmed.ncbi.nlm.nih.gov/?term=Si+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Wei Zhong](https://pubmed.ncbi.nlm.nih.gov/?term=Zhong+W&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Yan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Mengzhao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+M&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#full-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.") Affiliations Expand ### Affiliations * 1 Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 2 Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 3 Department of International Medical Service, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 4 Center for Health Policy and Health Economics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. * PMID: **42670654** * DOI: [ 10.1111/1759-7714.70386 ](https://doi.org/10.1111/1759-7714.70386) Item in Clipboard # Delayed Occurrence of Lung Cancer Leptomeningeal Metastasis and Era-Associated Post-LM Survival: A 14-Year Single-Center Cohort Study Xiaoxing Gao et al. Thorac Cancer. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Thorac Cancer Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Thorac+Cancer%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Thorac+Cancer%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42670654/) . 2026 Sep;17(17):e70386. doi: 10.1111/1759-7714.70386. ### Authors [Xiaoxing Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Jie Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+J&cauthor_id=42670654)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-2 "Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Qiuyue Ye](https://pubmed.ncbi.nlm.nih.gov/?term=Ye+Q&cauthor_id=42670654)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-3 "Department of International Medical Service, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Chen Wei](https://pubmed.ncbi.nlm.nih.gov/?term=Wei+C&cauthor_id=42670654)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-4 "Center for Health Policy and Health Economics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China."), [Qing Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Q&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Xiaoyan Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Minjiang Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+M&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Jing Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+J&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Hanping Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+H&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Xiaoyan Si](https://pubmed.ncbi.nlm.nih.gov/?term=Si+X&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Wei Zhong](https://pubmed.ncbi.nlm.nih.gov/?term=Zhong+W&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Yan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China."), [Mengzhao Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+M&cauthor_id=42670654)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670654/#short-view-affiliation-1 "Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.") ### Affiliations * 1 Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 2 Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 3 Department of International Medical Service, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China. * 4 Center for Health Policy and Health Economics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. * PMID: **42670654** * DOI: [ 10.1111/1759-7714.70386 ](https://doi.org/10.1111/1759-7714.70386) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Introduction:** Leptomeningeal metastasis (LM) is a devastating complication of lung cancer. We investigated the clinical and molecular evolution of LM in the modern targeted-therapy era and factors associated with post-LM survival. **Methods:** We retrospectively analyzed 201 patients with cytologically confirmed lung cancer LM diagnosed between November 2012 and May 2026. Patients were classified by LM diagnosis date (2012-2016 vs. 2017-2026). Intervals from lung cancer and Stage IV diagnosis to LM were compared using the Mann-Whitney U test. Paired primary tumor and cerebrospinal fluid (CSF) molecular profiles were assessed in 80 patients. Overall survival (OS) was evaluated using Kaplan-Meier and prespecified multivariable cox analyses. **Results:** Adenocarcinoma accounted for 93.0% of cases. The intervals from lung cancer and Stage IV diagnosis to LM were longer in the later cohort (23.7 vs. 13.8 months, p < 0.001; 17.4 vs. 10.4 months, p = 0.002). Unadjusted OS from LM diagnosis did not differ significantly between eras (9.8 vs. 11.3 months, p = 0.864). Tissue-CSF driver discordance occurred in 7/80 patients (8.75%). In multivariable analysis, later diagnostic era, smoking, and ECOG PS ≥ 2 were associated with higher mortality (adjusted HR, 1.826, p = 0.014; 1.847, p = 0.014; and 1.674, p = 0.007, respectively), whereas post-LM third-generation EGFR-TKI exposure was associated with lower mortality (adjusted HR, 0.385; p < 0.001). **Conclusion:** The later era was associated with a longer interval to LM diagnosis but no statistically significant improvement in unadjusted post-LM OS. Adjusted associations require cautious interpretation because of residual confounding and post-baseline treatment bias. CSF profiling may provide clinically relevant information beyond primary tumor genotyping. **Keywords:** cerebrospinal fluid; driver gene heterogeneity; leptomeningeal metastasis; lung cancer; real‐world study; targeted therapy. © 2026 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ A Retrospective Real-World Study of Prognostic Factors Associated With EGFR Mutated Lung Cancer With Leptomeningeal Metastasis. ](https://pubmed.ncbi.nlm.nih.gov/38418264/) Wu Y, Zhao Y, Wu Y, Chen H, Ma S, Wang Q.Wu Y, et al.Clin Lung Cancer. 2024 Jun;25(4):347-353.e1. doi: 10.1016/j.cllc.2024.02.001. Epub 2024 Feb 8.Clin Lung Cancer. 2024.PMID: 38418264 * [ Clinical outcomes of leptomeningeal metastasis in patients with non-small cell lung cancer in the modern chemotherapy era. ](https://pubmed.ncbi.nlm.nih.gov/22186628/) Park JH, Kim YJ,
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