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The Effect of Inflammatory Markers on Survival in Advanced Biliary Tract Carcinoma Treated with Gemcitabine/Oxaliplatin Regimen

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Abstract

Background

In advanced biliary tract carcinoma (BTC), the prognosis is very poor, and the overall survival is less than 1 year. This study aimed to determine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP)/albumin ratio (CAR), and prognostic nutritional index (PNI) on the survival of BTC patients treated with gemcitabine/oxaliplatin (GEMOX) regimen.

Methods

Data of 53 patients with advanced BTC were evaluated retrospectively. Association between inflammatory markers and 6-month PFS and 12-month OS were compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. NLR, dNLR, CAR, and PNI were grouped based on cutoff points 1.95, 1.15, 0.57, and 33, respectively. Univariate and multivariate analyses were used to assess their prognostic values for survival.

Results

Lower dNLR (< 1.15) was prognostic for higher 6-month PFS and 12-month OS rates, while lower NLR (< 1.95) was prognostic for higher 6-month PFS rates only. CAR and PNI did not have statistically significant effects on survival.

Conclusions

Pretreatment dNLR and NLR values in advanced BTC can be used as predictive markers for survival in patients undergoing the GEMOX regimen.

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References

  1. Jain A, Javle M. Molecular profiling of biliary tract cancer: a target rich disease. J Gastrointest Oncol. 2016;7:797–803.

    Article  Google Scholar 

  2. GBD. Mortality and causes of death collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2013;2015:117–71.

    Google Scholar 

  3. Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7(9):943–62.

    Article  CAS  Google Scholar 

  4. Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30(16):1934–40.

    Article  Google Scholar 

  5. Jordan E, Abou-Alfa GK, Lowery MA. Systemic therapy for biliary cancers. Chin Clin Oncol. 2016;5:65.

    Article  Google Scholar 

  6. Fiteni F, Jary M, Monnien F, et al. Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy. BMC Gastroenterol. 2014;14:143.

    Article  Google Scholar 

  7. McDonald B, Spicer J, Giannais B, et al. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int J Cancer. 2009;125:1298–305.

    Article  CAS  Google Scholar 

  8. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;7:1073–81.

    Article  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. Song S, Li C, Li S, Gao H, Lan X, Xue Y. Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer. Onco Targets Ther. 2017;10:3145–54.

    Article  Google Scholar 

  11. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;1:149–63.

    Article  Google Scholar 

  12. McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 2008;67:257–62.

    Article  Google Scholar 

  13. Ikeya T, Shibutani M, Maeda K, Sugano K, Nagahara H, Ohtani H, et al. Maintenance of the nutritional prognostic index predicts survival in patients with unresectable metastatic colorectal cancer. J Cancer Res Clin Oncol. 2015;141(2):307–13.

    Article  CAS  Google Scholar 

  14. Migita K, Takayama T, Saeki K, Matsumoto S, Wakatsuki K, Enomoto K, et al. The prognostic nutritional index predicts long-term outcomes of gastric cancer patients independent of tumor stage. Ann Surg Oncol. 2013;20(8):2647–54.

    Article  Google Scholar 

  15. Pinato DJ, North BV, Sharma R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer. 2012;106(8):1439–45.

    Article  CAS  Google Scholar 

  16. Fiteni F, Nguyen T, Vernerey D, Paillard MJ, Kim S, Demarchi M, et al. Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review. Cancer Med. 2014;3(6):1502–11.

    Article  CAS  Google Scholar 

  17. Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96(6):896–902.

    Article  CAS  Google Scholar 

  18. Jang JS, Lim HY, Hwang IG, Song HS, Yoo N, Yoon S, et al. Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean cancer study group phase II trial. Cancer Chemother Pharmacol. 2010;65(4):641–7.

    Article  CAS  Google Scholar 

  19. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

    Article  CAS  Google Scholar 

  20. Lee CH, Chang CJ, Lin YJ, Yeh CN, Chen MF, Hsieh SY. Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma. Br J Cancer. 2009;100:1765–70.

    Article  CAS  Google Scholar 

  21. Wehbe H, Henson R, Meng F, Mize-Berge J, Patel T. Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression. Cancer Res. 2006;66:10517–24.

    Article  CAS  Google Scholar 

  22. Powell DR, Huttenlocher A. Neutrophils in the tumor microenvironment. Trends Immunol. 2016;37(1):41–52.

    Article  CAS  Google Scholar 

  23. Zhao W, Wang P, Jia H, et al. Lymphocyte count or percentage: which can better predict the prognosis of advanced cancer patients following palliative care? BMC Cancer 2. 2017;17(1):514.

    Article  Google Scholar 

  24. McNamara MG, Templeton AJ, Maganti M, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014;50:1581–99.

    Article  CAS  Google Scholar 

  25. Cho KM, Park H, Oh DY, Kim TY, Lee KH, Han SW, et al. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer. Oncotarget. 2017;8(2):2329–41.

    Article  Google Scholar 

  26. Liu XF, Zhou LY, Wei ZH, Liu JX, Li A, Wang XZ, et al. The diagnostic role of circulating inflammation-based biomarker in gallbladder carcinoma. Biomark Med. 2018;12(10):1095–103.

    Article  CAS  Google Scholar 

  27. Song S, Chen H, Dong W, Zhou H. The prognostic value of preoperative derived neutrophil-to-lymphocyte ratio in patients undergoing total laryngectomy with laryngeal carcinoma. Acta Otolaryngol. 2019;139(3):294–8.

    Article  Google Scholar 

  28. Grenader T, Nash S, Plotkin Y, Furuse J, Mizuno N, Okusaka T, et al. Derived neutrophil lymphocyte ratio may predict benefit from cisplatin in the advanced biliary cancer: the ABC-02 and BT-22 studies. Ann Oncol. 2015;26(9):1910–6.

    Article  CAS  Google Scholar 

  29. Chen Z, Shao Y, Fan M, Zhuang Q, Wang K, Cao W, et al. Prognostic significance of preoperative C-reactive protein: albumin ratio in patients with clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2015;8:14893–900.

    PubMed  PubMed Central  Google Scholar 

  30. Fan Z, Fan K, Gong Y, Huang Q, Yang C, Cheng H, et al. The CRP/albumin ratio predicts survival and monitors chemotherapeutic effectiveness in patients with advanced pancreatic cancer. Cancer Manag Res. 2019;11:8781–8.

    Article  CAS  Google Scholar 

  31. Akgül Ö, Bagante F, Olsen G, Cloyd JM, Weiss M, Merath K, et al. Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection. J Surg Oncol. 2018;118(3):422–30.

    PubMed  Google Scholar 

  32. Miyazaki T, Sakai M, Sohda M, Tanaka N, Yokobori T, Motegi Y, et al. Prognostic significance of inflammatory and nutritional parameters in patients with esophageal cancer. Anticancer Res. 2016;36(12):6557–62.

    Article  CAS  Google Scholar 

  33. Geng Y, Qi Q, Sun M, Chen H, Wang P, Chen Z. Prognostic nutritional index predicts survival and correlates with systemic inflammatory response in advanced pancreatic cancer. Eur J Surg Oncol. 2015;41(11):1508–14.

    Article  CAS  Google Scholar 

  34. Takada A, Ohmori K, Yoneda T, Tsuyuoka K, Hasegawa A, Kiso M, et al. Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res. 1993;53(2):354–61.

    CAS  PubMed  Google Scholar 

  35. Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, Yoshidome H, et al. Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg. 2002;89(12):1525–31.

    Article  CAS  Google Scholar 

  36. Miwa S, Miyagawa S, Soeda J, Kawasaki S. Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinoma. Cancer. 2002;94(2):428–34.

    Article  CAS  Google Scholar 

  37. Briggs CD, Neal CP, Mann CD, Steward WP, Manson MM, Berry DP. Prognostic molecular markers in cholangiocarcinoma: a systematic review. Eur J Cancer. 2009;45(1):33–47.

    Article  CAS  Google Scholar 

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Correspondence to Mahmut Buyuksimsek.

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Buyuksimsek, M., Kidi, M.M., Ogul, A. et al. The Effect of Inflammatory Markers on Survival in Advanced Biliary Tract Carcinoma Treated with Gemcitabine/Oxaliplatin Regimen. J Gastrointest Canc 52, 249–255 (2021). https://doi.org/10.1007/s12029-020-00396-x

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