medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2013, Number 6

<< Back Next >>

Ann Hepatol 2013; 12 (6)

Prognostic implication of serum vascular endothelial growth factor in advanced hepatocellular carcinoma staging

Yegin EG, Siykhymbayev A, Eren F, Bekiroglu N, Cavit OO

Language: English
References: 48
Page: 915-925
PDF size: 137.33 Kb.


ABSTRACT

Background. Staging systems have considerable impact on hepatocellular carcinoma (HCC) treatment approaches and outcomes. There is an unmet need to improve their stratification ability. We have evaluated four commonly used staging systems and assessed whether angiogenic biomarker vascular endothelial growth factor (VEGF) could improve their prognostic stratification. Material and methods. Four staging systems; Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Child- Pugh were evaluated in 78 HCC patients; their stratification abilities were detected by Kaplan-Meier curves and log-rank test; their accuracies of predicting survival were compared with the concordance index. Serum VEGF levels were measured using ELISA method. Recursive partitioning was used to determine the optimal VEGF cutoff. The prognostic significance of VEGF cutoff and other parameters were analyzed using univariate and multivariate models. Results. None of the staging systems demonstrated better discriminatory ability in predicting survival. The four staging systems did not reveal significant differences in probability of survival across their intermediate-advanced stages. Optimal cutoff identified for VEGF was 445 pg/mL. In advanced HCC, VEGF level (p = 0.004) and in early HCC, bilirubin level (p = 0.009) were identified as the independent prognostic factors. Survival comparison with high and low VEGF levels was significant for advanced HCC, while insignificant for early disease. Conclusion. Staging systems with conventional parameters did not provide good prognostic stratification for survival in advanced HCC population. Serum VEGF level was an independent predictor of survival in advanced HCC, and provided more survival homogeneity within the advanced stages of conventional staging systems.


REFERENCES

  1. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001; 2: 533-43.

  2. Marrero JA. Hepatocellular carcinoma. Curr Opin Gastroenterol 2006; 22: 248-53.

  3. Motola-Kuba D, Zamora-Valdes D, Uribe M, Mendez-Sanchez N. Hepatocellular carcinoma. An overview. Ann Hepatol 2006; 5: 16-24.

  4. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340: 745-50.

  5. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009; 27: 1485-91.

  6. Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology 2008; 48: 137.

  7. El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 2002; 35: 72-8.

  8. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology 2004; 127: 35-50.

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

  10. Yang ZF, Poon RT. Vascular Changes in Hepatocellular Carcinoma. The Anatomical Record 2008; 291: 721-34.

  11. Huang GW, Yang LY, Lu WQ. Expression of hypoxiainducible factor 1alpha and vascular endothelial growth factor in hepatocellular carcinoma: impact on neovascularization and survival. World J Gastroenterol 2005; 11: 1705-8.

  12. Zhang ZL, Liu ZS, Sun Q. Expression of angiopoietins, Tie2 and vascular endothelial growth factor in angiogenesis and progression of hepatocellular carcinoma. World J Gastroenterol 2006; 12: 4241-5.

  13. Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and metaanalysis. Br J Cancer 2009; 100: 1385-92.

  14. Yao DF, Wu XH, Zhu Y, Shi GS, Dong ZZ, Yao DB, Wu W, et al. Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2005; 4: 220-6.

  15. Tseng CS, Lo HW, Chen PH, Chuang WL, Juan CC, Ker CG. Clinical significance of plasma D-dimer levels and serum VEGF levels in patients with hepatocellular carcinoma. Hepatogastroenterology 2004; 51: 1454-8.

  16. Poon RT, Ho JW, Tong CS, Lau C, Ng IO, Fan ST. Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg 2004; 91: 1354-60.

  17. Kamel L, Nessim I, Abd-el-Hady A, Ghali A, Ismail A. Assessment of the clinical significance of serum vascular endothelial growth factor and matrix metalloproteinase-9 in patients with hepatocellular carcinoma. J Egypt Soc Parasitol 2005; 35: 875-90.

  18. Chao Y, Li CP, Chau GY, Chen CP, King KL, Lui WY, Yen SH, et al. Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery. Ann Surg Oncol 2003; 10: 355-62.

  19. Poon RT, Lau C, Yu WC, Fan ST, Wong J. High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study. Oncol Rep 2004; 11: 1077-84.

  20. Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol 2004; 10: 2878-82.

  21. Wildi S, Pestalozzi BC, McCormack L, Clavien PA. Critical evaluation of the different staging systems for hepatocellular carcinoma. Br J Surg 2004; 91: 400-8.

  22. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985; 56: 918-28.

  23. CLIP Group. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 1998; 28: 751-5.

  24. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999; 19: 329-38.

  25. Chen CH, Hu FC, Huang GT, Lee PH, Tsang YM, Cheng AL, Chen DS, et al. Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method-analysis of 2010 Taiwanese patients. Eur J Cancer 2009; 45: 1630-9.

  26. Lu W, Dong J, Huang Z, Guo D, Liu Y, Shi S. Comparison of four current staging systems for Chinese patients with hepatocellular carcinoma undergoing curative resection: Okuda, CLIP, TNM and CUPI. J Gastroenterol Hepatol 2008; 23: 1874-8.

  27. Farinati F, Sergio A, Baldan A, Giacomin A, Di Nolfo MA, Del Poggio P, Benvegnu L, et al. Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study. BMC Cancer 2009; 9: 33.

  28. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-2.

  29. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-90.

  30. Collette S, Bonnetain F, Paoletti X, Doffoel M, Bouché O, Raoul JL, Rougier P, et al. Prognosis of advanced hepatocellular carcinoma: Comparison of three staging systems in two French clinical trials. Ann Oncol 2008; 19: 1117-26.

  31. Guglielmi A, Ruzzenente A, Pachera S, Valdegamberi A, Sandri M, D’Onofrio M, Iacono C. Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response. Am J Gastroenterol 2008; 103: 597-604.

  32. Kondo K, Chijiiwa K, Nagano M, Hiyoshi M, Kai M, Maehara N, Ohuchida J, et al. Comparison of seven prognostic staging systems in patients who undergo hepatectomy for hepatocellular carcinoma. Hepatogastroenterology 2007; 54: 1534-8.

  33. Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B, Rapaccini GL, et al. Prognostic factors for survival in patients with early intermediate hepatocellular carcinoma undergoing non-surgical therapy: Comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut 2005; 54: 411-8.

  34. Cillo U, Bassanello M, Vitale A, Grigoletto FA, Burra P, Fagiuoli S, D’Amico F, et al. The critical issue of hepatocellular carcinoma prognostic classification: Which is the best tool available? J Hepatol 2004; 40: 124-31.

  35. Levy I, Sherman M; Liver Cancer Study Group of the University of Toronto. Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut 2002; 50: 881-5.

  36. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, et al. EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421–30.

  37. Singhal A, Jayaraman M, Dhanasekaran DN, Kohli V. Molecular and serum markers in hepatocellular carcinoma: Predictive tools for prognosis and recurrence. Crit Rev Oncol Hematol 2012; 82: 116-40.

  38. Befeler AS, Di Bisceglie AM. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 2002; 122: 1609-19.

  39. Poon RT, Ng IO, Lau C, Zhu LX, Yu WC, Lo CM, Fan ST, et al. Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study. Ann Surg 2001; 233: 227-35.

  40. Jinno K, Tanimizu M, Hyodo I, Nishikawa Y, Hosokawa Y, Doi T, Endo H, et al. Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma. J Gastroenterol 1998; 33: 376-82.

  41. Kaseb AO, Hassan MM, Lin E, Xiao L, Kumar V, Pathak P, Lozano R, et al. V-CLIP: Integrating plasma vascular endothelial growth factor ýnto a new scoring system to stratify patients with advanced hepatocellular carcinoma for clinical trials. Cancer 2011; 117: 2478-88.

  42. Kaseb AO, Morris JS, Hassan MM, Siddiqui AM, Lin E, Xiao L, Abdalla EK, et al. Clinical and prognostic ýmplications of plasma ýnsulin-like growth factor-1 and vascular endothelial growth factor in patients with hepatocellular carcinoma. J Clin Oncol 2011; 29: 3892-9.

  43. Niizeki T, Sumie S, Torimura T, Kurogi J, Kuromatsu R, Iwamoto H, Aino H, et al. Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy. J Gastroenterol 2012; 47: 686-95.

  44. Ho MC, Chen CN, Lee H, Hsieh FJ, Shun CT, Chang CL, Lai YT, et al. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma. Cancer Lett 2007; 250: 237-49.

  45. Poon RTP, Lau C, Pang R, Ng KK, Yuen J, Fan ST. High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann Surg Oncol 2007; 14: 1835–45.

  46. Treiber G, Wex T, Rocken C, Fostitsch P, Malfertheiner P. Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 2006;132: 699-708.

  47. Poon RT, Lau CP, Cheung ST, Yu WC, Fan ST. Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Res 2003; 63: 3121-6.

  48. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, 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.




2020     |     www.medigraphic.com