Lung cancer is one of the most common oncological diseases with the highest mortality rate. Immunotherapy, given alone or in combination with chemotherapy, is the first-line treatment of choice for most patients with metastatic non-small cell lung cancer. The role of systemic inflammation leading to the dissemination and development of cancer is known. The subject of the present literature review are the markers of systemic inflammation, in the form of indices and scores, developed in recent years as prognostic and predictive factors for response to treatment in patients with metastatic lung cancer treated with immunotherapy.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. doi: 10.3322/caac.21660.
Flores R, Patel P, Alpert N, Pyenson B, Taioli E. Association of stage shift and population mortality among patients with non-small cell lung cancer. JAMA Netw Open. 2021;4(12):e2137508. doi: 10.1001/jamanetworkopen.2021.37508.
Paesmans M. Prognostic and Predictive Factors for Lung Cancer. Breathe. 2012;9(2):112-21. doi: 10.1183/20734735.006911.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-Related Inflammation. Nature. 2008;454(7203):436-44. doi: 10.1038/nature07205.
Khusnurrokhman G, Wati FF. Tumor-Promoting Inflammation in Lung Cancer: A Literature Review. Ann Med Surg (Lond). 2022;79:104022. doi: 10.1016/j.amsu.2022.104022.
Isaksson J, Wennstrom L, Branden E, Koyi H, Berglund A, Micke P, et al. Highly elevated systemic inflammation is a strong independent predictor of early mortality in advanced non-small cell lung cancer. Cancer Treat Res Commun. 2022;31:100556. doi: 10.1016/j.ctarc.2022.100556.
Altorki NK, Markowitz GJ, Gao D, Port JL, Saxena A, Stiles B, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19(1):9-31. doi: 10.1038/s41568-018-0081-9.
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446-54. doi: 10.1038/nature25183.
Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-Related Inflammation and Treatment Effectiveness. Lancet Oncol. 2014;15(11):e493-503. doi: 10.1016/S1470-2045(14)70263-3.
Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20(5):576-90. doi: 10.1016/j.ccr.2011.09.009.
Erpenbeck L, Schön MP. Deadly allies: the fatal interplay between platelets and metastasizing cancer cells. Blood. 2010;115(17):3427-36. doi: 10.1182/blood-2009-10-247296.
Placke T, Salih HR, Kopp H-G. Gitr ligand provided by thrombopoietic cells inhibits nk cell antitumor activity. J Immunol. 2012;189(1):154-60. doi: 10.4049/jimmunol.1103194.
Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. The J Clin Investig. 2013;123(8):3446-58. doi: 10.1172/JCI67484.
Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214-21.
Baracos VE, Martin L, Korc M, Guttridge DC, Fearon KCH. Cancer-associated cachexia. Nat Rev Dis Primers. 2018;4(1):17105. doi: 10.1038/nrdp.2017.105.
Mandaliya H, Jones M, Oldmeadow C, Nordman, II. Prognostic Biomarkers in stage iv non-small cell lung cancer (NSCLC): neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), Platelet to lymphocyte ratio (PLR) and Advanced lung cancer inflammation index (ALI). Transl Lung Cancer Res. 2019;8(6):886-94. doi: 10.21037/tlcr.2019.11.16.
Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer. 2012;107(4):695-9. doi: 10.1038/bjc.2012.292.
Yilmaz H, Yersal Ö. Prognostic significance of novel inflammatory markers in extensive-stage small-cell lung cancer. J Cancer Res Ther. 2022;18(3):691-6. doi: 10.4103/jcrt.jcrt_1937_21.
Gu XB, Tian T, Tian XJ, Zhang XJ. Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung cancer: a meta-analysis. Sci Rep. 2015;5(1):12493. doi: 10.1038/srep12493.
Krenn-Pilko S, Langsenlehner U, Thurner EM, Stojakovic T, Pichler M, Gerger A, et al. The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients. Br J Cancer. 2014;110(10):2524-30. doi: 10.1038/bjc.2014.163.
Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III Colon Cancer. Br J Cancer. 2014;110(2):435-40. doi: 10.1038/bjc.2013.785.
Limaye AR, Clark V, Soldevila-Pico C, Morelli G, Suman A, Firpi R, et al. Neutrophil-Lymphocyte ratio predicts overall and recurrence-free survival after liver transplantation for hepatocellular carcinoma. Hepatol Res. 2013;43(7):757-64. doi: 10.1111/hepr.12019.
Hu K, Lou L, Ye J, Zhang S. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open. 2015;5(4):e006404. doi: 10.1136/bmjopen-2014-006404.
Zhang X, Zhang W, Feng LJ. Prognostic significance of neutrophil lymphocyte ratio in patients with gastric cancer: a meta-analysis. PLoS One. 2014;9(11):e111906. doi: 10.1371/journal.pone.0111906.
Petrova MP, Eneva MI, Arabadjiev JI, Conev NV, Dimitrova EG, Koynov KD, et al. Neutrophil to lymphocyte ratio as a potential predictive marker for treatment with pembrolizumab as a second line treatment in patients with non-small cell lung cancer. Biosci Trends. 2020;14(1):48-55. doi: 10.5582/bst.2019.01279.
Romano FJ, Ronga R, Ambrosio F, Arundine D, Longo V, Galetta D, et al. Neutrophil-to-lymphocyte ratio is a major prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Cancer Diagn Progn. 2023;3(1):44-52. doi: 10.21873/cdp.10178.
Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-22. doi: 10.1158/1078-0432.CCR-14-0442.
Yang R, Chang Q, Meng X, Gao N, Wang W. Prognostic Value of systemic immune-inflammation index in cancer: a meta-analysis. J Cancer. 2018;9(18):3295-302. doi: 10.7150/jca.25691.
Guo D, Zhang J, Jing W, Liu J, Zhu H, Fu L, et al. Prognostic value of systemic immune-inflammation index in patients with advanced non-small-cell lung cancer. Future Oncol. 2018;14(25):2643-50. doi: 10.2217/fon-2018-0285.
Tomita M, Ayabe T, Maeda R, Nakamura K. Systemic immune-inflammation index predicts survival of patients after curative resection for non-small cell lung cancer. In Vivo. 2018;32(3):663-7. doi: 10.21873/invivo.11291.
Dan L, Xia Y, He Y, Weimin L. Prognostic value of systemic immune inflammation index in advanced non small cell lung cancer. D62 types, genotypes, and phenotypes: the three "T's" of thoracic oncology. American Thoracic Society International Conference Abstracts. American Thoracic Society; 2018. p. A7331-A.
Tong YS, Tan J, Zhou XL, Song YQ, Song YJ. Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer. J Transl Med. 2017;15(1):221. doi: 10.1186/s12967-017-1326-1.
Hong X, Cui B, Wang M, Yang Z, Wang L, Xu Q. Systemic immune-inflammation index, based on platelet counts and neutrophil-lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer. Tohoku J Exp Med. 2015;236(4):297-304. doi: 10.1620/tjem.236.297.
Bilgetekin I, Basal FB. Systemic immune-inflammation index is the best prognostic factor in patients with advanced stage adenocarcinoma of the lung treated with pemetrexed. J Coll Physicians Surg Pak. 2020;30(9):933-9. doi: 10.29271/jcpsp.2020.09.933.
Berardi R, Santoni M, Rinaldi S, Bower M, Tiberi M, Morgese F, et al. Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small cell lung cancer. Ann Transl Med. 2019;7(20):572. doi: 10.21037/atm.2019.09.18.
Zhang Y, Chen B, Wang L, Wang R, Yang X. Systemic immune-inflammation index is a promising noninvasive marker to predict survival of lung cancer: a meta-analysis. Medicine. 2019;98(3):e13788. doi: 10.1097/md.0000000000013788.
Wang Y, Li Y, Chen P, Xu W, Wu Y, Che G. Prognostic value of the pretreatment systemic immune-inflammation index (sii) in patients with non-small cell lung cancer: a meta-analysis. Ann Transl Med. 2019;7(18):433. doi: 10.21037/atm.2019.08.116.
Hang W, Luo J, Wen J, Jiang M. The relationship between systemic immune inflammatory index and prognosis of patients with non-small cell lung cancer: a meta-analysis and systematic review. Front Surg. 2022;9:898304. doi: 10.3389/fsurg.2022.898304.
Liu J, Li S, Zhang S, Liu Y, Ma L, Zhu J, et al. Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio can predict clinical outcomes in patients with metastatic non-small-cell lung cancer treated with nivolumab. J Clin Lab Anal. 2019;33(8):e22964. doi: 10.1002/jcla.22964.
Xu H, Feng H, Zhang W, Wei F, Zhou L, Liu L, et al. Prediction of immune-related adverse events in non-small cell lung cancer patients treated with immune checkpoint inhibitors based on clinical and hematological markers: real-world evidence. Exp Cell Res. 2022;416(1):113157. doi: 10.1016/j.yexcr.2022.113157.
Mahiat C, Bihin B, Duplaquet F, Stanciu Pop C, Dupont M, Vander Borght T, et al. Systemic inflammation/nutritional status scores are prognostic but not predictive in metastatic non-small-cell lung cancer treated with first-line immune checkpoint inhibitors. Int J Mol Sci. 2023;24(4):3618. doi: 10.3390/ijms24043618.
Fang Q, Yu J, Li W, Luo J, Deng Q, Chen B, et al. Prognostic value of inflammatory and nutritional indexes among advanced nsclc patients receiving PD-1 inhibitor therapy. Clin Exp Pharmacol Physiol. 2023;50(2):178-90. doi: 10.1111/1440-1681.13740.
Mountzios G, Samantas E, Senghas K, Zervas E, Krisam J, Samitas K, et al. Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer. ESMO Open. 2021;6(5):100254. doi: 10.1016/j.esmoop.2021.100254.
Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902-7. doi: 10.1182/blood-2007-10-116327.
Bjørnhart B, Hansen K, Jørgensen T, Herrstedt J, Schytte T. Ep1.04-29 Khorana Score: a potential new biomarker for real life non-small cell lung cancer (nsclc) patients treated with immunotherapy. J Thorac Oncol. 2019;14(10):S980-S1. doi: 10.1016/j.jtho.2019.08.2154.