Adjuvant sorafenib therapy in patients with resected hepatocellular carcinoma: evaluation of predictive factors
Tóm tắt
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.
Tài liệu tham khảo
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
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.
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.
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.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.
Chen J, Gao J. Advances in the study of molecularly targeted agents to treat hepatocellular carcinoma. Drug Discov Ther. 2014;8:154–64.
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.
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.
Wang Z, Zhang G, Wu J, Jia M. Adjuvant therapy for hepatocellular carcinoma: current situation and prospect. Drug Discov Ther. 2014;7:137–43.
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.
Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Lee DH, Jacobs DR Jr. Association between serum gamma-glutamyltransferase and C-reactive protein. Atherosclerosis. 2005;178:327–30.
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.
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.
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.
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.
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.
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.
Seton-Rogers S. Tumour microenvironment: means of resistance. Nat Rev Cancer. 2013;13:607.
Masuda S, Izpisua Belmonte JC. The microenvironment and resistance to personalized cancer therapy. Nat Rev Clin Oncol. 2013;10:64.
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.
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.
Llovet JM, Bruix J. Molecular targeted therapies in hepatocellular carcinoma. Hepatology. 2008;48:1312–27.
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.