Lung Immune Prognostic Index (Lipi) As Prognostic Markers For Advanced Non-Small-Cell Lung Cancer (Nsclc) Treated With Immunotherapy: A Systematic Review And Meta-Analysis
Article Sidebar
Main Article Content
Abstract
The Lung Immune Prognostic Index (LIPI), based on the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) levels, has been recognized as an important prognostic biomarker in lung cancer. However, its prognostic value in patients with non–small cell lung cancer (NSCLC) has not been extensively discussed. Objective: This systematic review and meta-analysis aimed to comprehensively evaluate the association between LIPI and survival outcomes in patients with advanced-stage NSCLC receiving immunotherapy. Systematic literature search was conducted across PubMed, ScienceDirect, Cochrane Library, SSRN, Epistemonikos, and Google Scholar databases up to January 10, 2025. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Data were extracted for qualitative and quantitative synthesis, including pooled analyses and subgroup analyses. Random-effects models were applied to pool hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association between LIPI and progression-free survival (PFS) and/or overall survival (OS) in patients with advanced NSCLC treated with immunotherapy. A total of 7,551 patients from 13 studies were included in the analysis. Pooled analysis demonstrated that patients with poor or intermediate LIPI scores, compared with those with good LIPI scores, had significantly shorter PFS (HR = 2.20, 95% CI: 1.83–2.63, P < 0.001; HR = 1.47, 95% CI: 1.31–1.65, P < 0.001) and worse OS (HR = 3.31, 95% CI: 2.70–4.06, P < 0.001; HR = 1.88, 95% CI: 1.58–2.23, P < 0.001). Subgroup analyses based on immunotherapy type (monotherapy versus combination therapy) yielded consistent results. This study demonstrates that poor and intermediate LIPI scores are significantly associated with worse prognosis in patients with advanced-stage NSCLC receiving immunotherapy. Therefore, LIPI may serve as a promising non-invasive prognostic biomarker for predicting survival outcomes in this patient population. Keywords: lung immune prognostic index, LIPI, non–small cell lung cancer, immunotherapy.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
References
Aldea, M., Benitez, J. C., & Mezquita, L. (2020). The Lung Immune Prognostic Index (LIPI) stratifies prognostic groups in advanced non-small cell lung cancer (NSCLC) patients. Translational Lung Cancer Research, 9(4), 967.
Antonia, S. J., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., Yokoi, T., Chiappori, A., Lee, K. H., & de Wit, M. (2017). Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. New England Journal of Medicine, 377(20), 1919–1929.
Asmara, O. D., Hardavella, G., Ramella, S., Petersen, R. H., Tietzova, I., Boerma, E. C., Tenda, E. D., Bouterfas, A., Heuvelmans, M. A., & van Geffen, W. H. (2024). Stage III NSCLC treatment options: too many choices. Breathe, 20(3).
Carril-Ajuria, L., Lavaud, P., Dalban, C., Negrier, S., Gravis, G., Motzer, R. J., Chevreau, C., Tannir, N. M., Oudard, S., & McDermott, D. F. (2024). Validation of the Lung Immune Prognostic Index (LIPI) as a prognostic biomarker in metastatic renal cell carcinoma. European Journal of Cancer, 204, 114048.
Coffelt, S. B., Wellenstein, M. D., & de Visser, K. E. (2016). Neutrophils in cancer: neutral no more. Nature Reviews Cancer, 16(7), 431–446.
Felip, E., Altorki, N., Zhou, C., Csőszi, T., Vynnychenko, I., Goloborodko, O., Luft, A., Akopov, A., Martinez-Marti, A., & Kenmotsu, H. (2021). Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. The Lancet, 398(10308), 1344–1357.
Forde, P. M., Spicer, J., Lu, S., Provencio, M., Mitsudomi, T., Awad, M. M., Felip, E., Broderick, S. R., Brahmer, J. R., & Swanson, S. J. (2022). Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. New England Journal of Medicine, 386(21), 1973–1985.
Gauci, M.-L., Lanoy, E., Champiat, S., Caramella, C., Ammari, S., Aspeslagh, S., Varga, A., Baldini, C., Bahleda, R., & Gazzah, A. (2019). Long-term survival in patients responding to anti–PD-1/PD-L1 therapy and disease outcome upon treatment discontinuation. Clinical Cancer Research, 25(3), 946–956.
Hiam-Galvez, K. J., Allen, B. M., & Spitzer, M. H. (2021). Systemic immunity in cancer. Nature Reviews Cancer, 21(6), 345–359.
Li, Y., Yan, B., & He, S. (2023). Advances and challenges in the treatment of lung cancer. Biomedicine & Pharmacotherapy, 169, 115891.
Liu, H., Yang, X.-L., Yang, X.-Y., Dong, Z.-R., Chen, Z.-Q., Hong, J.-G., & Li, T. (2021). The prediction potential of the pretreatment lung immune prognostic index for the therapeutic outcomes of immune checkpoint inhibitors in patients with solid cancer: a systematic review and meta-analysis. Frontiers in Oncology, 11, 691002.
Lv, J., Zhou, Z., Wang, J., Yu, H., Lu, H., Yuan, B., Han, J., Zhou, R., Zhang, X., & Yang, X. (2019). Prognostic value of lactate dehydrogenase expression in different cancers: a meta-analysis. The American Journal of the Medical Sciences, 358(6), 412–421.
Mezquita, L., Auclin, E., Ferrara, R., Charrier, M., Remon, J., Planchard, D., Ponce, S., Ares, L. P., Leroy, L., & Audigier-Valette, C. (2018). Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non–small cell lung cancer. JAMA Oncology, 4(3), 351–357.
Petrelli, F., Cabiddu, M., Coinu, A., Borgonovo, K., Ghilardi, M., Lonati, V., & Barni, S. (2015). Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncologica, 54(7), 961–970.
Restrepo, J. C., Martínez Guevara, D., Pareja López, A., Montenegro Palacios, J. F., & Liscano, Y. (2024). Identification and application of emerging biomarkers in treatment of non-small-cell lung cancer: Systematic review. Cancers, 16(13), 2338.
Rojiani, M. V, & Rojiani, A. M. (2024). Non-small cell lung cancer—Tumor biology. In Cancers (Vol. 16, Number 4, p. 716). MDPI.
Shao, X., Hua, S., Feng, T., Ocansey, D. K. W., & Yin, L. (2022). Hypoxia-regulated tumor-derived exosomes and tumor progression: a focus on immune evasion. International Journal of Molecular Sciences, 23(19), 11789.
Wu, Y.-L., Tsuboi, M., He, J., John, T., Grohe, C., Majem, M., Goldman, J. W., Laktionov, K., Kim, S.-W., & Kato, T. (2020). Osimertinib in resected EGFR-mutated non–small-cell lung cancer. New England Journal of Medicine, 383(18), 1711–1723.
Yang, R., Zhong, L., Yang, X., Jiang, K., Li, L., Song, H., & Liu, B. (2016). Neutrophil elastase enhances the proliferation and decreases apoptosis of leukemia cells via activation of PI3K/Akt signaling. Molecular Medicine Reports, 13(5), 4175–4182.
Zhang, M., Hao, J., Wu, Y., Gao, Z., & Wang, M. (2024). Value of the lung immune prognostic index in patients with advanced small cell lung cancer treated with programmed death-ligand 1 and programmed death-1 inhibitors in the Chinese alpine region. Frontiers in Oncology, 14, 1411548.
Zhao, S., Zhang, P., Niu, S., Xie, J., Liu, Y., Liu, Y., Zhao, N., Cheng, C., & Lu, P. (2024). Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data. Functional & Integrative Genomics, 24(2), 72.