Role of Systemic Immunoinflammation Landscape in the Overall Survival of Patients with Leptomeningeal Metastases from Lung Cancer

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2023 Mar 30

PMID 36993872

Authors

Jia-Wei Wang

Qing Yuan

Li Li

Kai-Hua Cao

Qi Liu

Hong-Liang Wang

Ke Hu

Xi Wu

Jing-Hai Wan

Affiliations

Soon will be listed here.

Abstract

Purpose: Several biomarkers, such as baseline neutrophil-to-lymphocyte ratio (NLR), have been more investigated in patients with brain metastases (BM), while their role in patients with leptomeningeal metastases (LM) has not been clarified. Considering the difference between the clinical behaviour of BM and LM, there is the need for addressing the role of these biomarkers in LM.

Methods: The present study retrospectively analyzed 95 consecutive patients with LM from lung cancer who were diagnosed at the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences between January 2016 and December 2019. Baseline NLR, platelet-to-lymphocyte ratio (PLR), systemic immunoinflammation index (SII), and lymphocyte-to-monocyte ratio at diagnosis of LM were calculated based on complete blood count and correlated, along with other characteristics, with overall survival (OS) using univariate and multivariate analyses. The best cutoff values for systemic immunoinflammation biomarkers were derived using the surv_cutpoint function in R software, which optimized the significance of the split between Kaplan-Meier survival curves.

Results: Median OS of patients with LM was 12 months (95% CI 9-17 months). On univariate analysis, NLR, PLR, SII, LMR, sex, smoking history, ECOG performance status (PS) scores, histological subtypes and targeted therapy were all significantly associated with OS. Only NLR (=0.034, 95% CI 1.060-4.578) and ECOG PS scores (=0.019, 95% CI 0.137-0.839) maintained a significant association with OS on multivariate analysis. Furthermore, patients with baseline NLR >3.57 had significantly worse OS than patients with NLR ≤3.57 (median OS 7 vs 17 months), as did patients with ECOG PS scores >2 vs ≤2 (median OS 4 vs 15 months).

Conclusion: Both baseline NLR and PS scores at the time of LM diagnosis are helpful and available prognostic biomarkers for patients with LM from lung cancer.

Citing Articles

Craniospinal irradiation for leptomeningeal metastasis of solid tumors: survival analysis and prognostic factors.

Takeda K, Umezawa R, Yamamoto T, Takahashi N, Jingu K J Radiat Res. 2024; 65(5):667-675.

PMID: 39154378 PMC: 11420835. DOI: 10.1093/jrr/rrae059.

References

Boire A, Brastianos P, Garzia L, Valiente M . Brain metastasis. Nat Rev Cancer. 2019; 20(1):4-11. DOI: 10.1038/s41568-019-0220-y. View

Yuan Q, Wang S, Zhang G, He J, Liu Z, Wang M . Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma. Immun Inflamm Dis. 2021; 9(4):1618-1630. PMC: 8589354. DOI: 10.1002/iid3.515. View

Suh J, Kotecha R, Chao S, Ahluwalia M, Sahgal A, Chang E . Current approaches to the management of brain metastases. Nat Rev Clin Oncol. 2020; 17(5):279-299. DOI: 10.1038/s41571-019-0320-3. View

Lin Y, Wei K, Chen P, Lim M, Hwang T . Roles of Neutrophils in Glioma and Brain Metastases. Front Immunol. 2021; 12:701383. PMC: 8411705. DOI: 10.3389/fimmu.2021.701383. View

Gonzalez H, Hagerling C, Werb Z . Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018; 32(19-20):1267-1284. PMC: 6169832. DOI: 10.1101/gad.314617.118. View

Sperduto P, Yang T, Beal K, Pan H, Brown P, Bangdiwala A . Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA). JAMA Oncol. 2016; 3(6):827-831. PMC: 5824323. DOI: 10.1001/jamaoncol.2016.3834. View

Le Rhun E, Wallet J, Mailliez A, Cecile Le Deley M, Rodrigues I, Boulanger T . Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer. Neuro Oncol. 2019; 22(4):524-538. PMC: 7158648. DOI: 10.1093/neuonc/noz201. View

Nanjo S, Hata A, Okuda C, Kaji R, Okada H, Tamura D . Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer. Br J Cancer. 2017; 118(1):32-37. PMC: 5765232. DOI: 10.1038/bjc.2017.394. View

Naidoo J, Schreck K, Fu W, Hu C, Carvajal-Gonzalez A, Connolly R . Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers. J Immunother Cancer. 2021; 9(8). PMC: 8359453. DOI: 10.1136/jitc-2021-002473. View

10.

Hiam-Galvez K, Allen B, Spitzer M . Systemic immunity in cancer. Nat Rev Cancer. 2021; 21(6):345-359. PMC: 8034277. DOI: 10.1038/s41568-021-00347-z. View

11.

Chua W, Charles K, Baracos V, Clarke S . Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011; 104(8):1288-95. PMC: 3078587. DOI: 10.1038/bjc.2011.100. View

12.

Zhang L, Hu Y, Chen W, Tian Y, Xie Y, Chen J . Pre-stereotactic radiosurgery neutrophil-to-lymphocyte ratio is a predictor of the prognosis for brain metastases. J Neurooncol. 2020; 147(3):691-700. DOI: 10.1007/s11060-020-03477-w. View

13.

Alexander M, Lin E, Cheng H . Leptomeningeal Metastases in Non-small Cell Lung Cancer: Optimal Systemic Management in NSCLC With and Without Driver Mutations. Curr Treat Options Oncol. 2020; 21(9):72. DOI: 10.1007/s11864-020-00759-3. View

14.

Jiang B, Li Y, Guo W, Zhang X, Chen Z, Su J . Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells. Clin Cancer Res. 2017; 23(18):5480-5488. DOI: 10.1158/1078-0432.CCR-17-0047. View

15.

Capone M, Giannarelli D, Mallardo D, Madonna G, Festino L, Grimaldi A . Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer. 2018; 6(1):74. PMC: 6048712. DOI: 10.1186/s40425-018-0383-1. View

16.

Chowdhary M, Switchenko J, Press R, Jhaveri J, Buchwald Z, Blumenfeld P . Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery. J Neurooncol. 2018; 139(3):689-697. PMC: 6126986. DOI: 10.1007/s11060-018-2914-5. View

17.

Shaked Y . The pro-tumorigenic host response to cancer therapies. Nat Rev Cancer. 2019; 19(12):667-685. DOI: 10.1038/s41568-019-0209-6. View

18.

Palmisciano P, Watanabe G, Conching A, Ogasawara C, Vojnic M, DAmico R . Intrathecal therapy for the management of leptomeningeal metastatic disease: a scoping review of the current literature and ongoing clinical trials. J Neurooncol. 2022; 160(1):79-100. DOI: 10.1007/s11060-022-04118-0. View

19.

Ozcan G, Singh M, Vredenburgh J . Leptomeningeal Metastasis from Non-Small Cell Lung Cancer and Current Landscape of Treatments. Clin Cancer Res. 2022; 29(1):11-29. DOI: 10.1158/1078-0432.CCR-22-1585. View

20.

Mitsuya K, Nakasu Y, Kurakane T, Hayashi N, Harada H, Nozaki K . Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of worse survival after resection in patients with brain metastasis. J Neurosurg. 2016; 127(2):433-437. DOI: 10.3171/2016.8.JNS16899. View