Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis

Abstract Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. We investigated the survival outcomes of patients with NSCLC who received combined antiangiogenic and systemic therapies before and after LM progressio...

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Main Authors: Xiao-dan Zhu, Re-ha-ti Amanjiaoer, Yan-li Shen, Na Li, Mi-hray Abdurazik, Chun-ling Liu, Gang Sun
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-91922-z
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author Xiao-dan Zhu
Re-ha-ti Amanjiaoer
Yan-li Shen
Na Li
Mi-hray Abdurazik
Chun-ling Liu
Gang Sun
author_facet Xiao-dan Zhu
Re-ha-ti Amanjiaoer
Yan-li Shen
Na Li
Mi-hray Abdurazik
Chun-ling Liu
Gang Sun
author_sort Xiao-dan Zhu
collection DOAJ
description Abstract Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. We investigated the survival outcomes of patients with NSCLC who received combined antiangiogenic and systemic therapies before and after LM progression and explored survival-associated factors. Patients with epidermal growth factor receptor (EGFR)-mutant or wild-type NSCLC-LM receiving systemic therapy were included. Survival outcomes were analyzed separately for patients who received different therapies before and after LM progression. The primary outcomes were the median time from NSCLC diagnosis to LM (LM-free survival [mLFS]) and overall survival (mOS). The mLFS and mOS of the 77 enrolled patients after receiving EGFR-tyrosine kinase inhibitor (TKI) plus antiangiogenic drugs were 19.0 and 21.9 months, respectively, which were significantly longer than those of the patients in the EGFR-TKI monotherapy group (14.0 and 8.3 months, respectively; P values for mLFS and mOS were 0.035 and 0.038, respectively). In patients receiving platinum-based chemotherapy, significantly longer mLFS and mOS were not dependent on antiangiogenic therapy. Metastatic counts at more than three sites were associated with a shorter LFS, and liver metastasis was an independent predictor of worse OS. Combining antiangiogenic and systemic therapies, particularly EGFR-TKIs, may prolong LFS and OS in NSCLC-LM, whereas metastatic counts at more than three sites and liver metastasis may be adverse prognostic factors.
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spelling doaj-art-dc3eff0e9d90491c8fdcb2ac6cfcb3142025-08-20T03:10:06ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-91922-zCombination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasisXiao-dan Zhu0Re-ha-ti Amanjiaoer1Yan-li Shen2Na Li3Mi-hray Abdurazik4Chun-ling Liu5Gang Sun6Department of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Pulmonary Medicine, Xinjiang Medical University Affiliated Tumor Hospital, The Second WardDepartment of Breast and Thyroid Surgery, People’s Hospital of Xinjiang Uygur Autonomous RegionAbstract Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. We investigated the survival outcomes of patients with NSCLC who received combined antiangiogenic and systemic therapies before and after LM progression and explored survival-associated factors. Patients with epidermal growth factor receptor (EGFR)-mutant or wild-type NSCLC-LM receiving systemic therapy were included. Survival outcomes were analyzed separately for patients who received different therapies before and after LM progression. The primary outcomes were the median time from NSCLC diagnosis to LM (LM-free survival [mLFS]) and overall survival (mOS). The mLFS and mOS of the 77 enrolled patients after receiving EGFR-tyrosine kinase inhibitor (TKI) plus antiangiogenic drugs were 19.0 and 21.9 months, respectively, which were significantly longer than those of the patients in the EGFR-TKI monotherapy group (14.0 and 8.3 months, respectively; P values for mLFS and mOS were 0.035 and 0.038, respectively). In patients receiving platinum-based chemotherapy, significantly longer mLFS and mOS were not dependent on antiangiogenic therapy. Metastatic counts at more than three sites were associated with a shorter LFS, and liver metastasis was an independent predictor of worse OS. Combining antiangiogenic and systemic therapies, particularly EGFR-TKIs, may prolong LFS and OS in NSCLC-LM, whereas metastatic counts at more than three sites and liver metastasis may be adverse prognostic factors.https://doi.org/10.1038/s41598-025-91922-zAntiangiogenicChemotherapyEpidermal growth factor receptorLeptomeningeal metastasisNon-small cell lung cancer
spellingShingle Xiao-dan Zhu
Re-ha-ti Amanjiaoer
Yan-li Shen
Na Li
Mi-hray Abdurazik
Chun-ling Liu
Gang Sun
Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
Scientific Reports
Antiangiogenic
Chemotherapy
Epidermal growth factor receptor
Leptomeningeal metastasis
Non-small cell lung cancer
title Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
title_full Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
title_fullStr Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
title_full_unstemmed Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
title_short Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis
title_sort combination of antiangiogenic and systemic therapy in advanced non small cell lung cancer before and after progression to leptomeningeal metastasis
topic Antiangiogenic
Chemotherapy
Epidermal growth factor receptor
Leptomeningeal metastasis
Non-small cell lung cancer
url https://doi.org/10.1038/s41598-025-91922-z
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