Skip to main content
Log in

Adjuvant sorafenib therapy in patients with resected hepatocellular carcinoma: evaluation of predictive factors

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Currently there is no predictor for survival after adjuvant sorafenib in patients with hepatocellular carcinoma (HCC) who have undergone curative resection. Thirty-eight patients who underwent curative resection of HCC received adjuvant sorafenib therapy between August 2009 and March 2012. Clinicopathological parameters including patient factors, tumor factors, liver background, and inflammatory factors (before surgery and dynamic changes after sorafenib therapy) were evaluated to identify predictors for overall survival (OS) and recurrence-free survival (RFS). The recurrence rate, mortality rate, and clinicopathological data were also compared. Increased NLR after sorafenib (HR = 3.199, 95 % CI 1.365–7.545, P = 0.008), increased GGT after sorafenib (HR = 3.204, 95 % CI 1.333–7.700, P = 0.009), and the presence of portal vein thrombosis (HR = 2.381, 95 % CI 1.064–5.328, P = 0.035) were risk factors related to RFS. By contrast, increased NLR after sorafenib was the only independent risk factor related to OS (HR = 4.647, 95 % CI 1.266–17.053, P = 0.021). Patients with increased NLR or increased GGT after sorafenib had a higher incidence of recurrence and death. Patients who had increased NLR tended to have higher preoperative levels of NLR and GGT. There were no differences in clinicopathological factors in patients with increased GGT and decreased GGT. In conclusion, increased NLR predicted a worse OS and RFS in patients with HCC who underwent curative resection with adjuvant sorafenib therapy. Increased GGT predicted a worse OS. NLR and GGT can be monitored dynamically before and after sorafenib therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  3. Tang ZY, Ye SL, Liu YK, et al. A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:187–96.

    Article  PubMed  Google Scholar 

  4. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.

    Article  CAS  PubMed  Google Scholar 

  5. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  6. Chen J, Gao J. Advances in the study of molecularly targeted agents to treat hepatocellular carcinoma. Drug Discov Ther. 2014;8:154–64.

    Article  CAS  PubMed  Google Scholar 

  7. Zhong Y, Liu B, Deng M, Xu R. Adjuvant systemic drug therapy and recurrence of hepatocellular carcinoma following curative resection. Drug Discov Ther. 2013;7:164–6.

    CAS  PubMed  Google Scholar 

  8. Printz C. Clinical trials of note. Sorafenib as adjuvant treatment in the prevention of disease recurrence in patients with hepatocellular carcinoma (HCC) (STORM). Cancer. 2009;115:4646.

    Article  PubMed  Google Scholar 

  9. Wang Z, Zhang G, Wu J, Jia M. Adjuvant therapy for hepatocellular carcinoma: current situation and prospect. Drug Discov Ther. 2014;7:137–43.

    Google Scholar 

  10. Zhang W, Zhao G, Wei K, et al. Adjuvant sorafenib reduced mortality and prolonged overall survival and post-recurrence survival in hepatocellular carcinoma patients after curative resection: a single-center experience. BioScience Trends. 2014;8:333–8.

    Article  PubMed  Google Scholar 

  11. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.

    Article  CAS  PubMed  Google Scholar 

  12. Pinato DJ, Stebbing J, Ishizuka M, et al. A novel and validated prognostic index in hepatocellular carcinoma: the inflammation based index (IBI). J Hepatol. 2012;57:1013–20.

    Article  PubMed  Google Scholar 

  13. Morimoto M, Numata K, Moriya S, et al. Inflammation-based prognostic score for hepatocellular carcinoma patients on sorafenib treatment. Anticancer Res. 2012;32:619–23.

    CAS  PubMed  Google Scholar 

  14. Ju MJ, Qiu SJ, Fan J, et al. Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio is a convenient prognostic marker for Child–Pugh A hepatocellular carcinoma after operation. J Gastroenterol. 2009;44:635–42.

    Article  CAS  PubMed  Google Scholar 

  15. Wang Z, Song P, Xia J, Inagaki Y, Tang W, Kokudo N. Can gamma-glutamyl transferase levels contribute to a better prognosis for patients with hepatocellular carcinoma? Drug Discov Ther. 2014;8:134–8.

    Article  PubMed  Google Scholar 

  16. Balta S, Demirkol S, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;109:3125–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Mano Y, Shirabe K, Yamashita Y, et al. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg. 2013;258:301–5.

    Article  PubMed  Google Scholar 

  18. Wei K, Wang M, Zhang W, Mu H, Song TQ. Neutrophil–lymphocyte ratio as a predictor of outcomes for patients with hepatocellular carcinoma undergoing TAE combined with Sorafenib. Med Oncol. 2014;31:969.

    Article  PubMed  Google Scholar 

  19. Peng W, Li C, Wen TF, et al. Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival. J Surg Res. 2014;192:402–8.

    Article  PubMed  Google Scholar 

  20. Dan J, Zhang Y, Peng Z, et al. Postoperative neutrophil-to-lymphocyte ratio change predicts survival of patients with small hepatocellular carcinoma undergoing radiofrequency ablation. PLoS ONE. 2013;8:e58184.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Bo S, Gambino R, Durazzo M, et al. Associations between gamma-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: a possible implication for oxidative stress. World J Gastroenterol. 2005;11:7109–17.

    CAS  PubMed  Google Scholar 

  22. Song P, Feng X, Zhang K, et al. Screening for and surveillance of high-risk patients with HBV-related chronic liver disease: promoting the early detection of hepatocellular carcinoma in China. Biosci Trends. 2014;7:1–6.

    Google Scholar 

  23. Lee YJ, Kim JK, Lee JH, Lee HR, Kang DR, Shim JY. Association of serum gamma-glutamyltransferase with C-reactive protein levels and white blood cell count in Korean adults. Clin Chem Lab Med. 2008;46:1410–5.

    CAS  PubMed  Google Scholar 

  24. Saijo Y, Utsugi M, Yoshioka E, et al. The relationship of gamma-glutamyltransferase to C-reactive protein and arterial stiffness. Nutr Metab Cardiovasc Dis. 2008;18:211–9.

    Article  CAS  PubMed  Google Scholar 

  25. Lee DH, Jacobs DR Jr. Association between serum gamma-glutamyltransferase and C-reactive protein. Atherosclerosis. 2005;178:327–30.

    Article  CAS  PubMed  Google Scholar 

  26. Chen TM, Lin CC, Huang PT, Wen CF. Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation. J Gastroenterol Hepatol. 2012;27:553–61.

    Article  CAS  PubMed  Google Scholar 

  27. Ohno Y, Nakashima J, Ohori M, Gondo T, Hatano T, Tachibana M. Followup of neutrophil-to-lymphocyte ratio and recurrence of clear cell renal cell carcinoma. J Urol. 2012;187:411–7.

    Article  PubMed  Google Scholar 

  28. Keizman D, Ish-Shalom M, Huang P, et al. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer. 2012;48:202–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kobayashi M, Kubo T, Komatsu K, et al. Changes in peripheral blood immune cells: their prognostic significance in metastatic renal cell carcinoma patients treated with molecular targeted therapy. Med Oncol. 2013;30:556.

    Article  PubMed  Google Scholar 

  30. Zhu XD, Zhang JB, Zhuang PY, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008;26:2707–16.

    Article  PubMed  Google Scholar 

  31. Sun Y, Campisi J, Higano C, et al. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med. 2012;18:1359–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Seton-Rogers S. Tumour microenvironment: means of resistance. Nat Rev Cancer. 2013;13:607.

    Article  CAS  PubMed  Google Scholar 

  33. Masuda S, Izpisua Belmonte JC. The microenvironment and resistance to personalized cancer therapy. Nat Rev Clin Oncol. 2013;10:64.

    Google Scholar 

  34. Motomura T, Shirabe K, Mano Y, et al. Neutrophil–lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013;58:58–64.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang W, Zhu XD, Sun HC, et al. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res. 2010;16:3420–30.

    Article  CAS  PubMed  Google Scholar 

  36. Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology. 2008;48:1312–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Fridlender ZG, Sun J, Kim S, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was supported by a Grant from the National Natural Science Foundation of China (No. 81101871 & No.81372635), a Grant from the Tianjin Municipal Science and Technology Commission (TSTC, No.14JCYBJC25200), and a Grant from the Major Programs of the National Natural Science Foundation of Tianjin (No. 11JCZDJC18800). Grants were also received from the Program for a New Generation of Exceptional Personnel of Tianjin Medical University Cancer Hospital and the Tianjin Medical University Cancer Institute and Hospital of the National Clinical Research Center for Cancer.

Conflict of interest

All authors declare that they do not have a commercial or other association that might pose a conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wei Zhang or Tianqiang Song.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Zhao, G., Wei, K. et al. Adjuvant sorafenib therapy in patients with resected hepatocellular carcinoma: evaluation of predictive factors. Med Oncol 32, 107 (2015). https://doi.org/10.1007/s12032-015-0549-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-015-0549-3

Keywords

Navigation