ORIGINAL RESEARCH ARTICLE
Association of Inflammatory Markers with Treatment Response in Immune Checkpoint Inhibitors
Received Date : 04 Sep 2023
Accepted Date : 03 Oct 2023
Available Online : 12 Oct 2023
Murat BARDAKÇIa, Öznur BALa, Fahriye Tuğba KÖŞa, Derya DEMİRTAŞ ESMERa,Emre HAFIZOĞLUa, Hilal KARAKAŞa, Muhammed Bülent AKINCIa, Bülent YALÇINa
aClinic of Medical Oncology, Ankara City Hospital, Ankara, Türkiye
Doi: 10.37047/jos.2023-99441 - Article's Language: EN
J Oncol Sci.Journal of Oncological Sciences. 2023;9(3):158-65.
ABSTRACT
Objective: The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are markers of systemic inflammation.
NLR and PLR can predict the treatment outcomes of metastatic cancer for patients treated with immune checkpoint inhibitors
(ICI). In this study, we investigated whether NLR or PLR is a better predictor of survival outcomes. Material and Methods: Between February
2016 and November 2021, 106 patients who had metastatic disease arising from different types of solid tumors treated with ICIs were retrospectively
evaluated. The cut-off values of the NLR and PLR were determined by performing ROC curve analysis. Cox regression analysis
was performed to evaluate the predictive role of NLR and PLR in progression-free survival (PFS). Results: The median age of patients was
62 years (range: 19-84 years), and 60.4% of patients were male. The cut-off values for NLR and PLR were 4.06 and 192.59, respectively. The
patients were divided into two groups (low/high) according to the cut-off values. The results of the univariate analysis showed that PFS was
significantly longer in the group with low NLR and PLR. High NLR [hazard ratio: 1.95, 95% confidence interval (CI): 1.20-3.15, p=0.006]
and ≥2 Eastern Cooperative Oncology Group performance status (hazard ratio: 2.62, 95% CI: 1.61-4.26, p<0.001) were independent negative
predictive factors for PFS in the multivariate Cox regression analysis. Conclusion: We found that PFS and disease control rate were significantly
better in patients with low NLR who were administered immunotherapy. NLR may be a better predictive marker than PLR in cancer
patients administered immunotherapy.
Keywords: Immunotherapy; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; survival
REFERENCES
- Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-461. [Crossref] [PubMed] [PMC]
- Rimm DL, Han G, Taube JM, et al. A Prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol. 2017;3(8):1051-1058. [Crossref] [PubMed] [PMC]
- Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104. [Crossref] [PubMed] [PMC]
- Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493-503. [Crossref] [PubMed]
- Yuan A, Hsiao YJ, Chen HY, et al. Opposite effects of M1 and M2 macrophage subtypes on lung cancer progression. Sci Rep. 2015 Sep;5:14273. [Crossref] [PubMed] [PMC]
- Tao H, Mimura Y, Aoe K, et al. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer. 2012;75(1):95-101. [Crossref] [PubMed]
- Templeton AJ, Ace O, McNamara MG, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1204-1212. [Crossref] [PubMed]
- Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218-230. [Crossref] [PubMed]
- Dall'Olio FG, Maggio I, Massucci M, Mollica V, Fragomeno B, Ardizzoni A. ECOG performance status ≥2 as a prognostic factor in patients with advanced non small cell lung cancer treated with immune checkpoint inhibitors-A systematic review and meta-analysis of real world data. Lung Cancer. 2020 Jul;145:95-104. [Crossref] [PubMed]
- Kugel CH 3rd, Douglass SM, Webster MR, et al. Age correlates with response to anti-pd1, reflecting age-related differences in intratumoral effector and regulatory T-Cell populations. Clin Cancer Res. 2018;24(21):5347-5356. [Crossref] [PubMed] [PMC]
- Wang S, He Z, Wang X, et al. Can tumor mutational burden determine the most effective treatment for lung cancer patients? Lung Cancer Manag. 2020;8(4):LMT21. [Crossref] [PubMed] [PMC]
- Zeng X, Zhu S, Xu C, et al. Effect of comorbidity on outcomes of patients with advanced non-small cell lung cancer undergoing anti-PD1 immunotherapy. Med Sci Monit. 2020 Sep;26:e922576. [Crossref] [PubMed] [PMC]
- Botticelli A, Cirillo A, Scagnoli S, et al. The agnostic role of site of metastasis in predicting outcomes in cancer patients treated with immunotherapy. Vaccines (Basel). 2020;8(2):203. [Crossref] [PubMed] [PMC]
- Bersanelli M, Brighenti M, Buti S, Barni S, Petrelli F. Patient performance status and cancer immunotherapy efficacy: a meta-analysis. Med Oncol. 2018;35(10):132. [Crossref] [PubMed]
- Spigel DR, McCleod M, Jotte RM, et al. Safety, efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non-small cell lung cancer, including patients aged 70 years or older or with poor performance status (CheckMate 153). J Thorac Oncol. 2019;14(9):1628-1639. [Crossref] [PubMed]
- Sacdalan DB, Lucero JA, Sacdalan DL. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Onco Targets Ther. 2018 Feb;11:955-965. [Crossref] [PubMed] [PMC]
- Russo A, Franchina T, Ricciardi G, et al. Dynamic changes of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) during treatment with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). American Society of Clinical Oncology. 2019 May;37:2596. [Crossref]
- Amaral S, Moura MC, Carvalho J, Chaves A, Jesus E, Sousa G. Prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors. Annals of Oncology. 2019;30(1):i3. [Crossref]
- Kartolo A, Holstead R, Khalid S, et al. Serum neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in prognosticating immunotherapy efficacy. Immunotherapy. 2020;12(11):785-798. [Crossref] [PubMed]
- Delgado J, Pereira A, Villamor N, López-Guillermo A, Rozman C. Survival analysis in hematologic malignancies: recommendations for clinicians. Haematologica. 2014;99(9):1410-1420. [Crossref] [PubMed] [PMC]
- Jeyakumar G, Kim S, Bumma N, et al. Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy. J Immunother Cancer. 2017;5(1):82. [Crossref] [PubMed] [PMC]
- Park W, Lopes G. Perspectives: neutrophil-to-lymphocyte ratio as a potential biomarker in immune checkpoint inhibitor for non-small-cell lung cancer. Clin Lung Cancer. 2019;20(3):143-147. [Crossref] [PubMed]
- Capone M, Giannarelli D, Mallardo D, et al. 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. [Crossref] [PubMed] [PMC]
- Xie X, Liu J, Yang H, et al. Prognostic value of baseline neutrophil-to-lymphocyte ratio in outcome of immune checkpoint inhibitors. Cancer Invest. 2019;37(6):265-274. [Crossref] [PubMed]
- Jin J, Yang L, Liu D, Li W. Association of the neutrophil to lymphocyte ratio and clinical outcomes in patients with lung cancer receiving immunotherapy: a meta-analysis. BMJ Open. 2020;10(6):e035031. [Crossref] [PubMed] [PMC]
- Ren F, Zhao T, Liu B, Pan L. Neutrophil-lymphocyte ratio (NLR) predicted prognosis for advanced non-small-cell lung cancer (NSCLC) patients who received immune checkpoint blockade (ICB). Onco Targets Ther. 2019 May;12:4235-4244. [Crossref] [PubMed] [PMC]
- Zer A, Sung MR, Walia P, et al. Correlation of neutrophil to lymphocyte ratio and absolute neutrophil count with outcomes with PD-1 axis inhibitors in patients with advanced non-small-cell lung cancer. Clin Lung Cancer. 2018;19(5):426-434.e1. [Crossref] [PubMed]
- Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. [Crossref] [PubMed]