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Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis

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Abstract

Purpose

To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM).

Methods

We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups.

Results

165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8–15.6 months) in the IP group versus 10.1 months (95% CI 5.3–14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003).

Conclusions

Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS.

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Data availability

The data supporting this study’s findings are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

LM:

Leptomeningeal metastasis

LUAC:

Lung adenocarcinoma

IP:

Intrathecal pemetrexed

PSM:

Propensity score matching

OS:

Overall survival

CI:

Confidence interval

HR:

Hazard ratio

ECOG PS:

Eastern Cooperative Oncology Group Performance Status

NSCLC:

Non-small cell lung cancer

BBB:

Blood–brain barrier

EGFR:

Epidermal growth factor receptor

CSF:

Cerebral spinal fluid

MTX:

Methotrexate

RCTs:

Randomized clinical trials

ITC:

Intrathecal chemotherapy

AEs:

Adverse events

MRI:

Magnetic resonance imaging

BM:

Brain metastases

SMD:

Standardized mean differences

ALK:

Anaplastic lymphoma kinase

ROS1:

ROS proto-oncogene 1

Kras:

Kirsten rat sarcoma viral oncogene homolog

CNS:

Central nervous system

RANO:

Response Assessment in Neuro-Oncology

ORR:

Objective response rate

DOR:

Disease control rate

TKIs:

Tyrosine kinase inhibitors

WBRT:

Whole-brain radiotherapy

SRT:

Stereotactic radiotherapy

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Acknowledgements

We want to thank the help from the professors of the Fujian Provincial Center for Disease Control and Prevention. This study was supported by the National Natural Science Foundation of China (Grant No. 82072565), the Fujian Provincial Health Systemic Innovation Project (Grant No. 2020CXA010), the Natural Science Foundation of Fujian Province (Grant No. 2023J01180), the Fujian Provincial Health Technology Project (Grant No. 2022QNA046), and the Startup Fund for Scientific Research of Fujian Medical University (Grant No. 2020QH1218).

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 82072565), the Fujian Provincial Health Systemic Innovation Project (Grant No. 2020CXA010), the Natural Science Foundation of Fujian Province (Grant No. 2023J01180), the Fujian Provincial Health Technology Project (Grant No. 2022QNA046), and the Startup Fund for Scientific Research of Fujian Medical University (Grant No. 2020QH1218).

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Author notes

  1. Yaping Hong and Qian Miao have contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China

    Yaping Hong, Qian Miao, Xinlong Zheng, Yiquan Xu, Yunjian Huang, Shengjia Chen, Zhangzhou Huang, Haipeng Xu, Kan Jiang, Qiaofeng Zhong, Longfeng Zhang, Xiaobin Zheng, Hongfu Zeng, Shanshan Yang, Yujing Li, Shihui Li, Wu Zhuang & Gen Lin

  2. Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, 350014, China

    Yaping Hong, Qian Miao, Xinlong Zheng, Yiquan Xu, Yunjian Huang, Shengjia Chen, Zhangzhou Huang, Haipeng Xu, Kan Jiang, Qiaofeng Zhong, Longfeng Zhang, Xiaobin Zheng, Hongfu Zeng, Shanshan Yang, Yujing Li, Shihui Li, Wu Zhuang & Gen Lin

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  1. Yaping Hong
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Contributions

All authors contributed to the study’s conception and design. GL and WZ developed the study concept. YH and QM performed material preparation and data collection. YH and XZ prepared data analysis, figures, and tables. The first draft of the manuscript was written by YH, and all authors commented on previous versions. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wu Zhuang or Gen Lin.

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The authors declare no competing interests.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Fujian Provincial Cancer Hospital (Fuzhou, China).

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Hong, Y., Miao, Q., Zheng, X. et al. Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis. J Neurooncol 165, 301–312 (2023). https://doi.org/10.1007/s11060-023-04483-4

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