Background: The role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in limited-stage small-cell lung cancer (LS-SCLC) remains controversial. Methods: Using pooled hazard ratios (HR) with 95% CIs, we assessed the correlation of pre-treatment NLR and PLR with overall survival (OS) and progression-free survival (PFS) in LS-SCLC. Publication bias was assessed by Begg’s and Egger’s tests. Results: Ten studies were enrolled in our meta-analysis. Pooled analyses showed that pre-treatment high NLR was significantly associated with poor OS (HR: 1.80) and PFS (HR: 1.69) in LS-SCLC patients. High pre-treatment PLR was also associated with shorter OS (HR: 1.52) and PFS (HR: 1.39) in LS-SCLC patients. Conclusion: Our meta-analysis suggests that high pre-treatment NLR or PLR may be negatively related to OS and PFS in LS-SCLC.

Keywords:

Papers of special note have been highlighted as: • of interest

References

1. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat. Rev. Dis. Primers 7(1), 3 (2021)
MedlineGoogle Scholar
2. Davis S, Stanley KE, Yesner R, Kuang DT, Morris JF. Small-cell carcinoma of the lung – survival according to histologic subtype: a Veterans Administration Lung Group study. Cancer 47(7), 1863–1866 (1981).
Medline CASGoogle Scholar
3. van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 378(9804), 1741–1755 (2011).
MedlineGoogle Scholar
4. Govindan R, Page N, Morgensztern D et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the Surveillance, Epidemiologic, and End Results database. J. Clin. Oncol. 24(28), 4539–4544 (2006).
MedlineGoogle Scholar
5. Horn L, Mansfield AS, Szczęsna A et al. IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N. Engl. J. Med. 379(23), 2220–2229 (2018).
Medline CASGoogle Scholar
6. Paz-Ares L, Dvorkin M, Chen Y et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet 394(10212), 1929–1939 (2019).
Medline CASGoogle Scholar
7. Takei H, Kondo H, Kondo H et al. Surgery for small cell lung cancer: a retrospective analysis of 243 patients from Japanese Lung Cancer Registry in 2004. J Thorac Oncol. 9(8), 1140–1145 (2014).
MedlineGoogle Scholar
8. Faivre-Finn C, Snee M, Ashcroft L et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 18(8), 1116–1125 (2017).
MedlineGoogle Scholar
9. Buccheri G, Ferrigno D. Prognostic factors of small cell lung cancer. Hematol. Oncol. Clin. North Am. 18(2), 445–460 (2004). • Some studies have found that certain clinicopathological factors are associated with prognosis in small-cell lung cancer (SCLC).
MedlineGoogle Scholar
10. Goldstraw P, Chansky K, Crowley J et al. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J. Thorac. Oncol. 11(1), 39–51 (2016).
MedlineGoogle Scholar
11. Foster NR, Mandrekar SJ, Schild SE et al. Prognostic factors differ by tumor stage for small cell lung cancer: a pooled analysis of North Central Cancer Treatment Group trials. Cancer 115(12), 2721–2731 (2009).
Medline CASGoogle Scholar
12. Reck M, Thatcher N, Smit EF et al. Baseline quality of life and performance status as prognostic factors in patients with extensive-stage disease small cell lung cancer treated with pemetrexed plus carboplatin vs etoposide plus carboplatin. Lung Cancer 78(3), 276–281 (2012).
MedlineGoogle Scholar
13. Anami S, Doi H, Nakamatsu K, Uehara T et al. Serum lactate dehydrogenase predicts survival in small-cell lung cancer patients with brain metastases that were treated with whole-brain radiotherapy. J. Radiat. Res. 60(2), 257–263 (2019).
Medline CASGoogle Scholar
14. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011). • Tumor-promoting inflammation is a hallmark of cancer.
Medline CASGoogle Scholar
15. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 141(1), 39–51 (2010).
Medline CASGoogle Scholar
16. de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 6(1), 24–37 (2006).
Medline CASGoogle Scholar
17. Lv Y, Zhang S, Liu Z, Tian Y, Liang N, Zhang J. Prognostic value of preoperative neutrophil to lymphocyte ratio is superior to systemic immune inflammation index for survival in patients with glioblastoma. Clin. Neurol. Neurosurg. 181, 24–27 (2019).
MedlineGoogle Scholar
18. Huang L, Jiang S, Shi Y. Prognostic significance of baseline neutrophil–lymphocyte ratio in patients with non-small-cell lung cancer: a pooled analysis of open phase III clinical trial data. Future Oncol. 18(14), 1679–1689 (2022).
CASGoogle Scholar
19. Fu Y, Chen X, Song Y et al. The platelet to lymphocyte ratio is a potential inflammatory marker predicting the effects of adjuvant chemotherapy in patients with stage II colorectal cancer. BMC Cancer 21(1), 792 (2021).
Medline CASGoogle Scholar
20. Hong YH, Kim SK, Lee JR, Suh CS. Utility of blood markers for predicting outcomes of fertility preservation in patients with breast cancer. Front. Endocrinol. 13, 803803 (2022).
MedlineGoogle Scholar
21. Zheng X, Ye B, Gou Y et al. Neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers to predict relapse and survival in posthepatectomy HBV-related hepatocellular carcinoma: a meta-analysis and preliminary immune perspective. Transl. Cancer Res. 10(3), 1261–1272 (2021).
Medline CASGoogle Scholar
22. Huang R, Wei Y, Hung RJ et al. Associated links among smoking, chronic obstructive pulmonary disease, and small cell lung cancer: a pooled analysis in the International Lung Cancer Consortium. EBioMedicine 2(11), 1677–1685 (2015). • SCLC is closely related to tobacco exposure. Chronic obstructive pulmonary disease is a common complication in smokers, and it is also an independent risk factor for SCLC.
MedlineGoogle Scholar
23. Houghton AM. Mechanistic links between COPD and lung cancer. Nat. Rev. Cancer 13(4), 233–245 (2013).
Medline CASGoogle Scholar
24. Kang MH, Go SI, Song HN et al. The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer. Br. J. Cancer 111(3), 452–460 (2014).
Medline CASGoogle Scholar
25. Lohinai Z, Bonanno L, Aksarin A et al. Neutrophil–lymphocyte ratio is prognostic in early stage resected small-cell lung cancer. PeerJ 7, e7232 (2019).
MedlineGoogle Scholar
26. Deng M, Ma X, Liang X, Zhu C, Wang M. Are pretreatment neutrophil–lymphocyte ratio and platelet–lymphocyte ratio useful in predicting the outcomes of patients with small-cell lung cancer? Oncotarget 8(23), 37200–37207 (2017).
MedlineGoogle Scholar
27. Yu Y, Wang L, Cao S et al. Pre-radiotherapy lymphocyte count and platelet-to-lymphocyte ratio may improve survival prediction beyond clinical factors in limited stage small cell lung cancer: model development and validation. Transl. Lung Cancer Res. 9(6), 2315–2327 (2020).
Medline CASGoogle Scholar
28. Chen C, Yang H, Cai D, Xiang L, Fang W, Wang R. Preoperative peripheral blood neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms predict the survival of patients with limited-stage small-cell lung cancer. Transl. Lung Cancer Res. 10(2), 866–877 (2021).
Medline CASGoogle Scholar
29. Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15), 2008–2012 (2000).
Medline CASGoogle Scholar
30. Wen Q, Meng X, Xie P, Wang S, Sun X, Yu J. Evaluation of factors associated with platinum-sensitivity status and survival in limited-stage small cell lung cancer patients treated with chemoradiotherapy. Oncotarget 8(46), 81405–81418 (2017).
MedlineGoogle Scholar
31. Zheng Y, Wang L, Zhao W et al. Risk factors for brain metastasis in patients with small cell lung cancer without prophylactic cranial irradiation. Strahlenther. Onkol. 194(12), 1152–1162 (2018).
MedlineGoogle Scholar
32. Bernhardt D, Aufderstrasse S, König L et al. Impact of inflammatory markers on survival in patients with limited disease small-cell lung cancer undergoing chemoradiotherapy. Cancer Manag. Res. 10, 6563–6569 (2018).
Medline CASGoogle Scholar
33. Suzuki R, Wei X, Allen PK, Cox JD, Komaki R, Lin SH. Prognostic significance of total lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in limited-stage small-cell lung cancer. Clin. Lung Cancer 20(2), 117–123 (2019).
MedlineGoogle Scholar
34. Zhang Q, Qu Y, Liu H et al. Initial platelet-to-lymphocyte count as prognostic factor in limited-stage small cell lung cancer. Biomark. Med. 13(4), 249–258 (2019).
CASGoogle Scholar
35. Hu Z, Wu W, Zhang X et al. Advanced lung cancer inflammation index is a prognostic factor of patients with small-cell lung cancer following surgical resection. Cancer Manag. Res. 13, 2047–2055 (2021).
Medline CASGoogle Scholar
36. Qi J, Zhang J, Ge X et al. The addition of peripheral blood inflammatory indexes to nomogram improves the predictive accuracy of survival in limited-stage small cell lung cancer patients. Front. Oncol. 11, 713014 (2021)
Medline CASGoogle Scholar
37. Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat. Rev. Cancer 20(11), 662–680 (2020).
Medline CASGoogle Scholar
38. Raftopoulou S, Valadez-Cosmes P, Mihalic ZN, Schicho R, Kargl J. Tumor-mediated neutrophil polarization and therapeutic implications. Int. J. Mol. Sci. 23(6), 3218 (2022).
Medline CASGoogle Scholar
39. Langiu M, Palacios-Acedo AL, Crescence L, Mege D, Dubois C, Panicot-Dubois L. Cancer and thrombosis: the new Bermuda Triangle in cancer research. Int. J. Mol. Sci. 23(3), 1257 (2022).
Medline CASGoogle Scholar
40. Teijeira Á, Garasa S, Gato M et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52(5), 856–871 (2020).
Medline CASGoogle Scholar
41. Sabrkhany S, Kuijpers MJE, Oude Egbrink MGA, Griffioen AW. Platelets as messengers of early-stage cancer. Cancer Metastasis Rev. 40(2), 563–573 (2021).
Medline CASGoogle Scholar
42. Sabrkhany S, Griffioen AW, Oude Egbrink MG. The role of blood platelets in tumor angiogenesis. Biochim. Biophys. Acta 1815(2), 189–196 (2011).
Medline CASGoogle Scholar
43. Cho MS, Bottsford-Miller J, Vasquez HG et al. Platelets increase the proliferation of ovarian cancer cells. Blood 120(24), 4869–4872 (2012).
Medline CASGoogle Scholar
44. Yuan X, Zheng Z, Liu F et al. A nomogram to predict the overall survival of patients with symptomatic extensive-stage small cell lung cancer treated with thoracic radiotherapy. Transl. Lung Cancer Res. 10(5), 2163–2171 (2021). • Neutrophil-to-lymphocyte ratio has also been identified as an independent prognostic factor in SCLC by multivariate analysis.
Medline CASGoogle Scholar
45. Huang LL, Hu XS, Wang Y et al. Survival and pretreatment prognostic factors for extensive-stage small cell lung cancer: a comprehensive analysis of 358 patients. Thorac. Cancer 12(13), 1943–1951 (2021).
MedlineGoogle Scholar
46. Yang N, Han X, Yu J, Shu W, Qiu F, Han J. Hemoglobin, albumin, lymphocyte, and platelet score and neutrophil-to-lymphocyte ratio are novel significant prognostic factors for patients with small-cell lung cancer undergoing chemotherapy. J. Cancer Res. Ther. 16(5), 1134–1139 (2020).
Medline CASGoogle Scholar
47. Qi WX, Xiang Y, Zhao S, Chen J. Assessment of systematic inflammatory and nutritional indexes in extensive-stage small-cell lung cancer treated with first-line chemotherapy and atezolizumab. Cancer Immunol. Immunother. 70(11), 3199–3206 (2021).
Medline CASGoogle Scholar
48. Kutlu Y, Aydin SG, Bilici A et al. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy. Medicine (Baltimore) 102(15), e33432 (2023).
Medline CASGoogle Scholar
49. Zhang Y, Chen B, Wang L, Wang Y, Yang X. Systemic immune-inflammation index is a promising noninvasive marker to predict survival of lung cancer: a meta-analysis. Medicine (Baltimore) 98(3), e13788 (2019). • Previous meta-analyses found that high pre-treatment neutrophil-to-lymphocyte ratio was associated with short overall and progression-free survival in extensive-stage SCLC, or in SCLC without distinction between limited- and extensive-stage SCLC.
MedlineGoogle Scholar
50. Lu Y, Jiang J, Ren C. The clinicopathological and prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in small cell lung cancer: a meta-analysis. PLOS ONE 15(4), e0230979 (2020).
Medline CASGoogle Scholar
51. Lv SHP, Wang Y, Huang L, Wang F, Zhou JG, Ma H. Meta-analysis of serum gastrin-releasing peptide precursor as a biomarker for diagnosis of small cell lung cancer. Asian Pac. J. Cancer Prev. 18(2), 391–397 (2017).
MedlineGoogle Scholar
52. Zhang X, Duan J, Wen Z et al. Are the Derived Indexes of Peripheral Whole Blood Cell Counts (NLR, PLR, LMR/MLR) Clinically Significant Prognostic Biomarkers in Multiple Myeloma? A Systematic Review And Meta-Analysis. Front Oncol. 23(11), 766672 (2021).
Google Scholar

Vol. 19, No. 18

Supplemental Materials

Metrics

Downloaded 66 times

History

Received 23 May 2022

Accepted 15 May 2023

Published online 5 June 2023

Published in print June 2023

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-0523

Author contributions

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualization: Y Cheng; methodology: S Zhang and Y Wang; formal analysis: S Zhang, Y Wang and Y Cheng; writing – original draft preparation: Y Cheng and S Zhang; writing – review and editing: S Zhang, Y Wang and Y Cheng.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

PDF download