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The ratio of hemoglobin to red cell distribution width predicts survival in patients with gastric cancer treated by neoadjuvant FLOT: a retrospective study

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Abstract

Background

Hemoglobin (HB) and red cell distribution width (RDW) are known to be prognostic in many cancer types. The HB-RDW ratio (HRR) is a new biomarker that has been shown to be predictive in some cancer types. However, the prognostic significance of HRR in patients with gastric cancer (GC) is unknown.

Aims

In this study, we aimed to demonstrate the prognostic importance of HRR in GC patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT).

Methods

Eighty-five GC patients who were treated with neoadjuvant FLOT in our center were included in the study, retrospectively. Associations between clinical and histopathological parameters with disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan–Meier curves and compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. Neutrophil–lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and HRR were grouped based on a cutoff points 3.05, 802, and 0.89, respectively. Univariate and multivariate analyses were used to assess their prognostic values for DFS and OS.

Results

Low NLR, low SII, and high HRR were found to be associated with longer DFS/OS. In univariate analysis, Eastern Cooperative Oncology Group performance status, grade, stage, response to neoadjuvant treatment, NLR, SII, and HRR were found to be significantly associated with DFS and OS. But in multivariate analysis, only HRR was demonstrated as an independent prognostic factor for DFS/OS (p 0.001, p 0.037, respectively).

Conclusions

HRR is a new biomarker that can predict DFS and OS in GC patients treated with neoadjuvant FLOT.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  2. Schulz C, Kullmann F, Kunzmann V, Fuchs M, Geissler M, Vehling-Kaiser U, Stauder H, Wein A, al-Batran SE, Kubin T, Schäfer C, Stintzing S, Giessen C, Modest DP, Ridwelski K, Heinemann V (2015) NeoFLOT: multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastro-esophageal junction or gastric adenocarcinoma—very good response predominantly in patients with intestinal type tumors. Int J Cancer 137:678–685. https://doi.org/10.1002/ijc.29403

    Article  CAS  PubMed  Google Scholar 

  3. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474. https://doi.org/10.1245/s10434-010-0985-4

    Article  PubMed  Google Scholar 

  4. Mellor KL, Powell AGMT, Lewis WG (2018) Systematic review and meta-analysis of the prognostic significance of neutrophil-lymphocyte ratio (NLR) after R0 gastrectomy for cancer. J Gastrointest Cancer 49(3):237–244. https://doi.org/10.1007/s12029-018-0127-y

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yang Y, Gao P, Song Y, Sun J, Chen X, Zhao J, Ma B, Wang Z (2016) The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: a meta-analysis. Eur J Surg Oncol 42(8):1176–1182. https://doi.org/10.1016/j.ejso.2016.05.029

    Article  CAS  PubMed  Google Scholar 

  6. Yang R, Chang Q, Meng X, Gao N, Wang W (2018) Prognostic value of systemic immune-inflammation index in cancer: a meta-analysis. J Cancer 9(18):3295–3302. https://doi.org/10.7150/jca.25691

    Article  PubMed  PubMed Central  Google Scholar 

  7. Vannella L, Lahner E, Osborn J, Annibale B (2013) Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther 37(4):375–382

    Article  CAS  PubMed  Google Scholar 

  8. Ray-Coquard I, Morère JF, Scotté F, Cals L, Antoine EC (2012) Management of anemia in advanced breast and lung cancer patients in daily practice: results of a French survey. Adv Ther 29(2):124–133

    Article  CAS  PubMed  Google Scholar 

  9. Li W, Li X, Wang M, Ge X, Li F, Huang B, Peng J, Li G, Lu L, Yu Z, Ma J, Xu L, Jin M, Si H, Wan R (2015) Association between red cell distribution width and the risk of heart events in patients with coronary artery disease. Exp Ther Med 9(4):1508–1514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xu WS, Qiu XM, Ou QS, Liu C, Lin JP, Chen HJ, Lin S, Wang WH, Lin SR, Chen J (2015) Red blood cell distribution width levels correlate with liver fibrosis and inflammation: a noninvasive serum marker panel to predict the severity of fibrosis and inflammation in patients with hepatitis B. Medicine (Baltimore) 94(10):e612. https://doi.org/10.1097/MD.0000000000000612

    Article  CAS  Google Scholar 

  11. Hu L, Li M, Ding Y et al (2017) Prognostic value of RDW in cancers: a systematic review and meta-analysis. Oncotarget 8(9):16027–16035. https://doi.org/10.18632/oncotarget.13784

    Article  PubMed  Google Scholar 

  12. Wei TT, Wang LL, Yin JR, Liu YT, Qin BD, Li JY, Yin X, Zhou L, Zhong RQ (2017) Relationship between red blood cell distribution width, bilirubin, and clinical characteristics of patients with gastric cancer. Int J Lab Hematol 39(5):497–501. https://doi.org/10.1111/ijlh.12675

    Article  PubMed  Google Scholar 

  13. Bozkaya Y, Kurt B, Gürler F (2019) A prognostic parameter in advanced non-small cell lung cancer: the ratio of hemoglobin-to-red cell distribution width. Int J Clin Oncol 24(7):798–806. https://doi.org/10.1007/s10147-019-01417-x

    Article  CAS  PubMed  Google Scholar 

  14. Tham T, Olson C, Wotman M, Teegala S, Khaymovich J, Coury J, Costantino P (2018) Evaluation of the prognostic utility of the hemoglobin-to- red cell distribution width ratio in head and neck cancer. Eur Arch Otorhinolaryngol 275(11):2869–2878

    Article  PubMed  Google Scholar 

  15. Sun P, Zhang F, Chen C et al (2016) The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China. Oncotarget 7(27):52650–42660

    Google Scholar 

  16. Al-Batran SE, Homann N, Pauligk C et al (2019) Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. https://doi.org/10.1016/S0140-6736(18)32557-1

    Article  Google Scholar 

  17. Mercadante S, Gebbia V, Marrazzo A, Filosto S (2000) Anemia in cancer: pathophysiology and treatment. Cancer Treat Rev 26(4):303–311

    Article  CAS  PubMed  Google Scholar 

  18. Huang XZ, Yang YC, Chen Y, Wu CC, Lin RF, Wang ZN, Zhang X (2019) Preoperative anemia or low hemoglobin predicts poor prognosis in gastric cancer patients: a meta-analysis. Dis Markers 2019:7606128. https://doi.org/10.1155/2019/7606128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Caro JJ, Salas M, Ward A, Goss G (2001) Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer 91:2214–2221

    Article  CAS  PubMed  Google Scholar 

  20. Obermair A, Handisurya A, Kaider A, Sevelda P, Kölbl H, Gitsch G (1998) The relationship of pretreatment serum hemoglobin level to the survival of epithelial ovarian carcinoma patients: a prospective review. Cancer 83:726–731

    Article  CAS  PubMed  Google Scholar 

  21. Liu X, Qiu H, Huang Y, Xu D, Li W, Li Y, Chen Y, Zhou Z, Sun X (2018) Impact of preoperative anemia on outcomes in patients undergoing curative resection for gastric cancer: a single-institution retrospective analysis of 2163 Chinese patients. Cancer Med 7(2):360–369. https://doi.org/10.1002/cam4.1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sawayama H, Iwatsuki M, Kuroda D, Toihata T, Uchihara T, Koga Y, Yagi T, Kiyozumi Y, Eto T, Hiyoshi Y, Ishimoto T, Baba Y, Miyamoto Y, Yoshida N, Baba H (2018) Total iron-binding capacity is a novel prognostic marker after curative gastrectomy for gastric cancer. Int J Clin Oncol 23(4):671–680

    Article  CAS  PubMed  Google Scholar 

  23. Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 18(4):243–259

    Article  CAS  PubMed  Google Scholar 

  24. Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 9(Suppl 5):10–17

    Article  CAS  PubMed  Google Scholar 

  25. Hirahara N, Matsubara T, Kawahara D, Mizota Y, Ishibashi S, Tajima Y (2016) Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma. Int J Clin Oncol 21(5):909–919

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hirahara N, Tajima Y, Fujii Y et al (2019) Comprehensive analysis of red blood cell distribution width as a preoperative prognostic predictor in gastric cancer. Anticancer Res 39(6):3121–3130. https://doi.org/10.21873/anticanres.13448

    Article  PubMed  Google Scholar 

  27. Cheng S, Han F, Wang Y et al (2017) The red distribution width and the platelet distribution width as prognostic predictors in gastric cancer. BMC Gastroenterol 17(1):163

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yazici P, Demir U, Bozkurt E, Isil GR, Mihmanli M (2017) The role of red cell distribution width in the prognosis of patients with gastric cancer. Cancer Biomark 18(1):19–25

    Article  CAS  PubMed  Google Scholar 

  29. Liu X, Chen S, Liu J et al (2017) Impact of systemic inflammation on gastric cancer outcomes. PLoS One 12(3):e0174085. https://doi.org/10.1371/journal.pone.0174085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Miyamoto R, Inagawa S, Sano N, Tadano S, Adachi S, Yamamoto M (2018) The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients. Eur J Surg Oncol 44(5):607–612. https://doi.org/10.1016/j.ejso.2018.02.003

    Article  PubMed  Google Scholar 

  31. Yu L, Lv CY, Yuan AH et al (2015) Significance of the preoperative neutrophil-to-lymphocyte ratio in the prognosis of patients with gastric cancer. World J Gastroenterol 21(20):6280–6286. https://doi.org/10.3748/wjg.v21.i20.6280

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chen L, Zuo Y, Zhu L et al (2017) Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy. Onco targets Ther 10:2569–2580

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, Zhang X, Wang WM, Qiu SJ, Zhou J, Fan J (2014) Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res 20(23):6212–6222

    Article  CAS  PubMed  Google Scholar 

  34. Hong X, Cui B, Wang M, Yang Z, Wang L, Xu Q (2015) 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 236(4):297–304

    Article  CAS  PubMed  Google Scholar 

  35. Wang K, Diao F, Ye Z et al (2017) Prognostic value of systemic immune-inflammation index in patients with gastric cancer. Chin J Cancer 36:75

    Article  PubMed  PubMed Central  Google Scholar 

  36. Huang L, Liu S, Lei Y, Wang K, Xu M, Chen Y, Liu B, Chen Y, Fu Q, Zhang P, Qin K, Cai Y, Fu S, Ge S, Yuan X (2016) Systemic immune-inflammation index, thymidine phosphorylase and survival of localized gastric cancer patients after curative resection. Oncotarget 7:44185–44193

    PubMed  PubMed Central  Google Scholar 

  37. Chen L, Yan Y, Zhu L et al (2017) Systemic immune–inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy. Cancer Manag Res 9:849–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Ali Yılmaz.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study protocol was approved by the local ethics committee (Approval number: 05/21-27.06.2019).

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Yılmaz, A., Mirili, C., Tekin, S.B. et al. The ratio of hemoglobin to red cell distribution width predicts survival in patients with gastric cancer treated by neoadjuvant FLOT: a retrospective study. Ir J Med Sci 189, 91–102 (2020). https://doi.org/10.1007/s11845-019-02153-x

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