Ahmet ERGİN, Esin AVCI, Burcu YAPAR TAŞKÖYLÜ, Serkan DEĞİRMENCİOĞLU, Derya KILIÇ, Gamze GÖKÖZ DOĞU, Arzu YAREN, Canan KARAN, Tolga DOĞAN, Burçin ÇAKAN, Melek ÖZDEMİR

Over kanserinde nötrofil/lenfosit, trombosit/lenfosit, CRP/Albümin oranları ile klinikopatolojik özellikler ve sağkalım arasındaki ilişki

Amaç: Over kanseri jinekolojik kanserler arasında en yüksek ölüm oranına sahip olan kanserdir. Birçok kanserde inflamasyon temelli skorlar olan nötrofil lenfosit oranının (NLR), trombosit lenfosit oranının (PLR), CRP albümin oranının (CRP/Alb) prognoz üzerine etkisi gösterilmiştir. Biz de bu çalışmada NLR, PLR, CRP/Alb oranlarının over kanserinin prognozu üzerine olan etkisini değerlendirmeyi amaçladık. Gereç ve yöntem: Çalışmamıza Eylül 2014-Aralık 2020 tarihleri arasında Pamukkale Üniversitesi Tıp Fakültesi Tıbbi Onkoloji Bilim Dalı polikliniğine başvuran over karsinom tanılı evreleri 1 ile 4 arasında değişen toplam 124 hasta dâhil edildi. NLR, PLR, CRP/Alb kesme noktaları ROC analizi ile yapıldı. Bulgular: Hastalarımızın medyan yaşı 56 (sınırlar 24-84) idi. NLR oranı 63 hastada(%50), PLR oranı 56 hastada (%45), CRP/Alb oranı 61 hastada (%49) kesme değerine göre yüksek saptandı. PLR değeri ile progresyon sağkalım arasında istatistiksel olarak anlamlı ilişki yokken, genel sağkalımla istatistiksel olarak anlamlı ilişki bulunmaktaydı (p=0,01). PLR değeri yüksek olanlarda medyan genel sağkalım 23 ay iken PLR değeri düşük olanlarda 45 ay olarak saptandı. CRP/Alb oranının ise hem progresyonsuz sağkalım hem de genel sağkalım ile istatistiksel olarak anlamlı ilişkisi mevcuttu (p=0,011; p=0,008). CRP/Alb değeri düşük olanlarda daha uzun progresyonsuz sağkalım ve genel sağkalım olduğu saptandı. Sonuç: Diğer kanser tiplerinde olduğu gibi over kanserinde de inflamasyon belirteçlerinin kanser progresyonu üzerine dolayısıyla prognoza olan etkisi dikkat çekmektedir. PLR oranının genel sağkalımla, CRP/Alb oranının ise hem genel sağkalım hemde progresyonsuz sağkalımla istatistiksel olarak anlamlı bir ilişkisi olduğunu gösterdik. Bu oranların gelecekte farklı tedavi gruplarını oluştururken hastaların seçiminde yardımcı olabileceği kanısındayız.

Relationship between neutrophil/lymphocyte, platelet/lymphocyte, CRP/Albumin ratio and survival in ovarian cancer

Purpose: Ovarian cancer has the highest mortality rate among gynecological cancers. Inflammation-based scores such as neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), CRP albumin ratio (CRP/Alb) have been shown to have an effect on prognosis in most cancers. In this study, we aimed to evaluate the effect of NLR, PLR, CRP/Albumin ratios on the prognosis of ovarian cancer. Material and method: A total of 124 patients with ovarian carcinoma diagnosed stages ranging from 1 to 4 were included in our study who applied to Pamukkale University Medical Faculty Medical Oncology Outpatient Clinic between September 2014 and December. NLR, PLR, CRP/Alb cut-off points were made by ROC analysis. Results: The median age of our patients was 56 (range 24-84). The NLR rate was higher in 63 patients (50%), the PLR rate in 56 patients (45%), and the CRP/Alb ratio in 61 patients (49%) compared to the cut-off value. While there was no statistically significant relationship between PLR value and progression free survival, there was a statistically significant relationship with overall survival (p=0.01). While the median overall survival was 23 months in those with high PLR values, it was 45 months in those with low PLR values. The CRP/Alb ratio had a statistically significant relationship with both progression free survival and overall survival (p=0.011; p=0.008). Longer progression free survival and overall survival were found in those with low CRP/Alb values. Conclusion: As in other cancer types, the effect of inflammation markers on cancer progression and thus on prognosis is remarkable in ovarian cancer. We showed that the PLR ratio has a statistically significant relationship with overall survival and the CRP/Alb ratio with both overall survival and progression free survival. We are of the opinion that these rates may help in the selection of patients while creating different treatment groups in the future.

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1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30. https://doi. org/10.3322/caac.21590
2. Morgan JrRJ, Armstrong DK, Alvarez RD, et al. Ovarian cancer, version 1.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 2016;14:1134-163. https://doi.org/10.6004/ jnccn.2016.0122
3. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Seminars in Surgical Oncology 2000;19:3-10. https:// doi.org/10.1002/1098-2388(200007/08)19:1<3::AIDSSU2> 3.0.CO;2-S
4. Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol. 2004;191:733-740. https://doi. org/10.1016/j.ajog.2004.03.035
5. Hainaut P, Plymoth A. Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer therapy. Curr Opin Oncol 2013;25:50-51. https://doi.org/10.1097/CCO.0b013e32835b651e
6. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357:539-545. https://doi. org/10.1016/S0140-6736(00)04046-0
7. Nie W, Yu T, Sang Y, Gao X. Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment. Biochem Biophys Res Commun 2017;482:1400-1406. https://doi.org/10.1016/j. bbrc.2016.12.048
8. He W, Yin C, Guo G, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol 2013;30:439. https://doi. org/10.1007/s12032-012-0439-x
9. Jung MR, Park YK, Jeong O, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J Surg Oncol 2011;104:504-10. https://doi. org/10.1002/jso.21986
10. Liu X, Qu JK, Zhang J, et al. Prognostic role of pretreatment neutrophil to lymphocyte ratio in breast cancer patients: a meta-analysis. Medicine 2017;96:e8101. https://doi.org/10.1097/ MD.0000000000008101
11. Gu XB, Tian T, Tian XJ, Zhang XJ. Prognostic significance of neutrophil-tolymphocyte ratio in nonsmall cell lung cancer: a meta-analysis. Sci Rep 2015;5:12493. https://doi.org/10.1038/srep12493
12. Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and metaanalysis. Ann Surg Oncol 2016;23:646-654. https://doi. org/10.1245/s10434-015-4869-5
13. Baert T, Van Camp J, Vanbrabant L, et al. Influence of CA125, platelet count and neutrophil to lymphocyte ratio on the immune system of ovarian cancer patients. Gynecol Oncol 2018;150:31-37. https://doi. org/10.1016/j.ygyno.2018.05.004
14. Zhu Y, Zhou S, Liu Y, Zhai L, Sun X. Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review. BMC Cancer 2018;18:443. https://doi. org/10.1186/s12885-018-4318-5
15. Marnell L, Mold C, Du Clos TW. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 2005;117:104-111. https://doi.org/10.1016/j. clim.2005.08.004
16. Hefler LA, Concin N, Hofstetter G, et al. Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer. Clin Cancer Res 2008;14:710-714. https://doi.org/10.1158/1078-0432. CCR-07-1044
17. Zeng F, Wei H, Yeoh E, et al. Inflammatory markers of CRP, IL6, TNFalpha, and soluble TNFR2 and the risk of ovarian cancer: a meta-analysis of prospective studies. Cancer Epidemiol Biomark Prev 2016;25:1231-1239. https://doi.org/10.1158/1055-9965.EPI-16-0120
18. Brower V. Feeding the flame: new research adds to role of inflammation in cancer development. J Natl Cancer Inst 2005;97:251-253. https://doi.org/10.1093/ jnci/97.4.251
19. Milne K, Alexander C, Webb JR, et al. Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes. J Transl Med 2012;10:33. https://doi.org/10.1186/1479- 5876-10-33
20. Williams KA, Intidhar LG, Terry KL, et al. Prognostic significance and predictors of the neutrophiltolymphocyteratio in ovarian cancer. Gynecol Oncol 2014;132:542-550. https://doi.org/10.1016/j. ygyno.2014.01.026
21. Wang YQ, Jin C, Zheng HM, et al. A novel prognostic inflammation score predicts outcomes in patients with ovarian cancer. Clin Chim Acta 2016;456:163-169. https://doi.org/10.1016/j.cca.2016.03.013
22. Yin X, Wu L, Yang H, Yang HB. Prognostic significance of neutrophil–lymphocyte ratio (NLR) in patients with ovarian cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e17475. https://doi. org/10.1097/MD.0000000000017475
23. Cho H, Hur HW, Kim SW, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated inepithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother 2009;58:15-23. https:// doi.org/10.1007/s00262-008-0516-3
24. Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Translat Oncol 2011;13:499- 503. https://doi.org/10.1007/s12094-011-0687-9
25. Zhang WW, Liu KJ, Hu GL, Liang WJ. Preoperative platelet/lymphocyte ratio is a superiorprognostic factor compared to other systemic inflammatory responsemarkers in ovarian cancer patients. Tumour Biol 2015;36:8831-8837. https://doi.org/10.1007/ s13277-015-3533-9
26. Tian C, Song W, TianX, Sun Y. Prognostic significance of platelet-to-lymphocyte ratio in patients with ovarian cancer: a meta-analysis. Eur J Clin Invest 2018;48:e12917. https://doi.org/10.1111/ eci.12917
27. Liu Y, Chen S, Zheng C, et al. The prognostic value of the preoperative c-reactive protein/albumin ratio in ovarian cancer. BMC Cancer 2017;17:285. https://doi. org/10.1186/s12885-017-3220-x
28. Komura N, Mabuchi S, Shimura K, Kawano M, Matsumoto Y, Kimura T. Significance of pretreatment C-reactive protein, albumin, and C-reactive protein to albumin ratio in predicting poor prognosis in epithelial Ovarian Cancer Patients. Nutr Cancer 2020:1-8. https://doi.org/10.1080/01635581.2020.1798479
29. Peres LC, Mallen AR, Townsend MK, et al. High levels of C-reactive protein are associated with an increased risk of ovarian cancer: results from the Ovarian Cancer Cohort Consortium. Cancer Res 2019;79:5442-5451. https://doi.org/10.1158/0008-5472.CAN-19-1554