Prognostic Significance of the Lymphocyte/Monocyte Ratio in Patients with Extensive Stage Small Cell Lung Cancer

Abstract

Purpose: Small cell lung cancer (SCLC) is a type of lung cancer that is sensitive to chemotherapy but has a poor prognosis. In this study, we aimed to investigate the prognostic significance of the lymphocyte / monocyte ratio and clinical and laboratory parameters.
Materials and Methods: In this study, medical records of 146 patients who were diagnosed with SCLC between January 2014 and December 2019 and were in the extensive stage were analyzed retrospectively. The lymphocyte / monocyte ratio (LMO) was calculated from the blood tests taken before chemotherapy.
Results: Median overall survival (OS) was 8.78 (range 1.07-54.80) months, progression-free survival (PFS) was 5.6 (1.07 - 44.03) months in the patients enrolled in the study. In the cohort analysis of all patients, the median PFS was 4.5 months, OS 7.5 months in the low group with LMO and 6.5 months, OS 10.1 months in the high group with LMO. When examined by univariate analysis, patients with high LMO also had longer OS than patients with low (HR 0.591 95% CI 0.42-0.83 p=0.003). When analyzed by multivariate analysis, LMO continued to be one of the good prognostic parameter for survival (HR: 0.54% 95 CI 0.38-0.77. p=0.001)
Conclusion: It has been shown that high LMO can be an independent prognostic parameter showing long PFS and OS in patients with extensive stage small cell lung cancer.

Keywords

• Lymphocyte / Monocyte Ratio
• Prognostic Factor
• Small Cell Lung Cancer (SCLC)
• Survival

Yaygın Evre Küçük Hücreli Akciğer Kanserinde Lenfosit/Monosit Oranının Prognostik Önemi

Abstract

Amaç: Küçük Hücreli akciğer kanseri (KHAK) kemoterapiye duyarlı ancak kötü prognozu olan bir akciğer kanseri türüdür. Bu çalışmamızda lenfosit/monosit oranının ile birlikte diğer klinik ve laboratuvar parametrelerinin prognostik önemini araştırmayı amaçladık.
Araçlar ve Yöntem: Bu çalışmamızda retrospektif olarak Ocak 2014 ile Aralık 2019 tarihleri arasında KHAK tanısı almış ve yaygın evrede olan 146 hastanın tıbbi kayıtları incelendi. Kemoterapi öncesi alınan kan tetkiklerinden lenfosit/monosit oranı (LMO) hesaplandı.
Bulgular: Çalışmaya alınan hastalarda medyan genel sağ kalım süresi 8.78 (aralık 1.07-54.80) ay, progresyonsuz sağ kalım süresi (PSK) 5.6 (1.07–44.03) ay olarak bulundu. Tüm hastaların kohort analizinde, LMO düşük grupta medyan PSK 4.5 ay, genel sağ kalım süresi (GSK) 7.5 ay olup, LMO yüksek grupta medyan PSK 6.5 ay, GSK 10.1 ay olarak saptandı. Tek değişkenli analiz ile incelendiğinde LMO yüksek olan hastaların düşük olan hastalara göre genel sağ kalım süreleri de daha uzundu (HR 0.591 %95 CI 0.42-0.83 p=0.003). Çok değişkenli analiz ile incelendiğinde ise LMO yüksekliği sağ kalım için iyi prognostik göstergelerden biri olma özelliğini devam ettiriyordu (HR: 0.54 %95 CI 0.38-0.77. p=0.001)
Sonuç: Yüksek LMO, yaygın evre küçük hücreli akciğer kanseri hastalarında uzun PSK ve GSK’yı gösteren bağımsız bir prognostik parametre olabileceği kanıtlandı.

Keywords

• LMO
• Prognostik faktör
• lenfosit/monosit oranı
• Küçük hücreli akciğer kanseri (KHAK)
• Sağkalım

References

1. 1. American Cancer Society. Key Statistics for Lung Cancer. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Erişim tarihi 20 Kasım, 2020.
2. 2. Rossi A, Di Maio M, Chiodini P, ve ark. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: The COCIS meta-analysis of individual patient data. Journal of Clinical Oncology. 2012;30(14):1692-1698.
3. 3. Lee GW, Go S Il, Kim DW, ve ark. Geriatric Nutritional Risk Index as a prognostic marker in patients with extensive-stage disease small cell lung cancer: Results from a randomized controlled trial. Thorac Cancer. 2020;11(1):62-71.
4. 4. Hiltermann TJN, Pore MM, Van den Berg A, ve ark. Circulating tumor cells in small-cell lung cancer: A predictive and prognostic factor. Annals of oncology. 2012;23(11):2937-2942.
5. 5. Huang L, Shi Y. Prognostic value of pretreatment smoking status for small cell lung cancer: A meta-analysis. Thoracic Cancer. 2020;11(11):3252-3259.
6. 6. Udagawa H, Umemura S, Murakami I, ve ark. Genetic profiling-based prognostic prediction of patients with advanced small-cell lung cancer in large scale analysis. Lung Cancer. 2018;126:182-188.
7. 7. Chen B, Li H, Liu C, ve ark. Potential prognostic value of delta-like protein 3 in small cell lung cancer: A meta-analysis. World journal of surgical oncology. 2020;18(1):1-9.
8. 8. Sagman U, Feld R, Evans WK, ve ark. The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer. J Clin Oncol. 1991;9(6):954-961.

9. 9. Rollins BJ. Inflammatory chemokines in cancer growth and progression. European journal of cancer. 2006;42(6):760-767.
10. 10. Studnicka M, Wirnsberger R, Neumann M, Pokieser L, Angerler J. Peripheral blood lymphocyte subsets and survival in small-cell lung cancer. Chest. 1994;105(6):1673–1678.
11. 11. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer - related inflammation. Nature. 2008;454(7203):436-444.
12. 12. Wilcox RA, Feldman AL, Wada DA, ve ark. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood. 2009;114(10):2149-2158.
13. 13. Porrata LF, Ristow KM, Habermann TM, ve ark. Peripheral blood absolute lymphocyte/monocyte ratio during rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone treatment cycles predicts clinical outcomes in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014;55(12):2728-2738.
14. 14. Go S-I, Kim RB, Song H-N, ve ark. Prognostic significance of the lymphocyte-to-monocyte ratio in patients with small cell lung cancer. Med Oncol. 2014;31(12):323.
15. 15. 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):886-894.
16. 16. D’Andrea D, Moschini M, Gust KM, ve ark. Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy. Journal of surgical oncology, 2017;115(4):455-461.
17. 17. Huszno J, Kołosza Z, Mrochem-Kwarciak J, Zajusz A. Prognostic Value of the Neutrophil-Lymphocyte, Platelet-Lymphocyte, and Monocyte-Lymphocyte Ratios in Male Breast Cancer Patients. Oncology. 2020;98(7):487-492.
18. 18. Organization WH. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. World Health Organization. https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_NHD_MNM_11.1_eng.pdf. Erişim tarihi 20 Kasım, 2020.
19. 19. Eisenhauer EA, Therasse P, Bogaerts J, ve ark. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.
20. 20. R. Fluss, D. Faraggi, and B. Reiser. Estimation of the Youden Index and its associated cutoff point. Journal of Mathematical Methods in Biosciences. 2005;47(4):458-472.
21. 21. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 3. 1973;4(2):31.
22. 22. Agra Y, Pelayo M, Sacristan M, Sacristán A, Serra C, Bonfill X. Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev. 2003;(4).
23. 23. L. Horn, AS Mansfield, A Szczęsna ve ark. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220-2229.
24. 24. Teramukai S, Kitano T, Kishida Y, ve ark. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: An analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45(11):1950-1958.
25. 25. Jakubowska K, Koda M, Grudzińska M, Kańczuga-Koda L, Famulski W. Monocyte-to-lymphocyte ratio as a prognostic factor in peripheral whole blood samples of colorectal cancer patients. World J Gastroenterol. 2020;26(31):4639.
26. 26. Shibutani M, Maeda K, Nagahara H, Iseki Y, Ikeya T, Hirakawa K. Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer. Oncol Lett. 2017;13(2):1000-1006.
27. 27. Eo WK, Chang HJ, Kwon SH, ve ark. The lymphocyte-monocyte ratio predicts patient survival and aggressiveness of ovarian cancer. J Cancer. 2016;7(3):289.
28. 28. Eo WK, Kwon S, Koh SB, ve ark. The lymphocyte-monocyte ratio predicts patient survival and aggressiveness of endometrial cancer. J Cancer. 2016;7(5):538.
29. 29. De Giorgi U, Mego M, Scarpi E, ve ark. Relationship Between Lymphocytopenia and Circulating Tumor Cells as Prognostic Factors for Overall Survival in Metastatic Breast Cancer. Clin Breast Cancer. 2012;12(4):264-269.
30. 30. Gooden MJM, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 2011;105(1):93-103.
31. 31. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4(1):71-78.