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Ki-67 is a Prognostic Biomarker of Survival after Radiofrequency Ablation of Liver Malignancies

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To assess the predictive value of examinations of tissue adherent to multitined electrodes on local tumor progression-free survival (LPFS) and overall survival (OS) after liver tumor radiofrequency ablation (RFA).

Methods

An institutional review board–approved, Health Insurance Portability and Accountability Act–compliant review identified 68 liver tumors treated with RFA in 63 patients with at least 3 years’ follow-up. Tissue adherent to the electrode after liver tumor RFA was evaluated with proliferation (Ki-67) and apoptotic (caspase-3) markers. LPFS and OS were evaluated by Kaplan–Meier methodology and the log-rank test. Multivariate analysis assessed the effect of tumor size, pathology, and post-RFA tissue characteristics on LPFS and OS.

Results

Post-RFA tissue examination classified 55 of the 68 tumors as completely ablated with coagulation necrosis, with cells positive for caspase-3 and negative for Ki-67 (CN). Thirteen had viable Ki-67-positive tumor cells. Mean liver tumor size was larger in the viable (V) group versus the CN group (3.4 vs. 2.5 cm, respectively; P = .017). For the V and CN groups, respectively, local tumor progression occurred in 12 (92 %) of 13 and 23 (42 %) of 55 specimens. One, 3-, and 5-year LPFS was 8 %, 8 %, and 8 %, and 79 %, 47 %, and 47 % (P < .001) for the V and CN groups, respectively. During a 63-month median follow-up, 92 % of patients in the V group and 58 % in the CN group died, resulting in 1-, 3-, and 5-year OS of 92 %, 25 %, and 8 % vs. 92 %, 59 %, and 33 % (P = .032), respectively.

Conclusions

Ki-67-positive tumor cells on the electrode after liver tumor RFA is an independent predictor of LPFS and OS. Size, initially thought to be an independent risk factor for local tumor progression in tumors 3–5 cm, does not hold its significance at long follow-up.

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References

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

    PubMed  CAS  Google Scholar 

  2. Hildebrand P, Kleemann M, Roblick UJ, et al. Radiofrequency-ablation of unresectable primary and secondary liver tumors: results in 88 patients. Langenbecks Arch Surg. 2006;391:1–6.

    Article  Google Scholar 

  3. Hanna NN. Radiofrequency ablation of primary and metastatic hepatic malignancies. Clin Colorectal Cancer. 2004;4:92–100.

    Article  PubMed  Google Scholar 

  4. Gillams AR. The use of radiofrequency in cancer. Br J Cancer. 2005;92:1825–9.

    Article  PubMed  CAS  Google Scholar 

  5. Curley SA, Izzo F. Radiofrequency ablation of primary and metastic liver tumors. Surg Technol Int. 2002;10:99–106.

    PubMed  Google Scholar 

  6. Chen MH, Yang W, Yan K, et al. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications. World J Gastroenterol. 2005;11:6395–401.

    PubMed  Google Scholar 

  7. Sofocleous CT, Nascimento RG, Gonen M, et al. Radiofrequency ablation in the management of liver metastases from breast cancer. Am J Roentgenol. 2007;189:883–9.

    Article  CAS  Google Scholar 

  8. Meloni MF, Andreano A, Laeseke PF, Livraghi T, Sironi S, Lee FT Jr. Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation—intermediate and long-term survival rates. Radiology. 2009;253:861–9.

    Article  PubMed  Google Scholar 

  9. Rhim H, Lim HK, Choi D. Current status of radiofrequency ablation of hepatocellular carcinoma. World J Gastrointest Surg. 2010;2:128–36.

    Article  PubMed  Google Scholar 

  10. Jakobs TF, Hoffmann RT, Schrader A, et al. CT-guided radiofrequency ablation in patients with hepatic metastases from breast cancer. Cardiovasc Intervent Radiol. 2009;32:38–46.

    Article  PubMed  Google Scholar 

  11. Sutherland LM, Williams JA, Padbury RT, Gotley DC, Stokes B, Maddern GJ. Radiofrequency ablation of liver tumors: a systematic review. Arch Surg. 2006;141:181–90.

    Article  PubMed  Google Scholar 

  12. Ng KK, Poon RT. Radiofrequency ablation for malignant liver tumor. Surg Oncol. 2005;14:41–52.

    Article  PubMed  Google Scholar 

  13. Rossi S, Garbagnati F, Lencioni R, et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology. 2000;217:119–26.

    PubMed  CAS  Google Scholar 

  14. Harrison LE, Koneru B, Bahramipour P, et al. Locoregional recurrences are frequent after radiofrequency ablation for hepatocellular carcinoma. J Am Coll Surg. 2003;197:759–64.

    Article  PubMed  Google Scholar 

  15. White RR, Avital I, Sofocleous CT, et al. Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis. J Gastrointest Surg. 2007;11:256–63.

    Article  PubMed  CAS  Google Scholar 

  16. Livraghi T, Solbiati L, Meloni MF, Gazelle EF, Goldberg SN. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology. 2003;226:441–51.

    Article  PubMed  Google Scholar 

  17. Lencioni R, Crocetti L, Cioni D, Della Pina C, Bartolozzi C. Percutaneous radiofrequency ablation of hepatic colorectal metastases: technique, indications, results, and new promises. Invest Radiol. 2004;39:689–97.

    Article  PubMed  Google Scholar 

  18. White TJ, Roy-Choudhury SH, Breen DJ, et al. Percutaneous radiofrequency ablation of colorectal hepatic metastases—initial experience. An adjunct technique to systemic chemotherapy for those with inoperable colorectal hepatic metastases. Dig Surg. 2004;21:314–20.

    Article  PubMed  CAS  Google Scholar 

  19. Siperstein A, Garland A, Engle K, et al. Laparoscopic radiofrequency ablation of primary and metastatic liver tumors. Technical considerations. Surg Endosc. 2000;14:400–5.

    Article  CAS  Google Scholar 

  20. Adam R, Hagopian EJ, Linhares M, et al. A comparison of percutaneous cryosurgery and percutaneous radiofrequency for unresectable hepatic malignancies. Arch Surg. 2002;137:1332–9.

    Article  PubMed  Google Scholar 

  21. Snoeren N, Jansen MC, Rijken AM, et al. Assessment of viable tumour tissue attached to needle applicators after local ablation of liver tumours. Dig Surg. 2009;26:56–62.

    Article  PubMed  Google Scholar 

  22. Sofocleous CT, Nascimento RG, Petrovic LM, et al. Histopathologic and immunohistochemical features of tissue adherent to multitined electrodes after RF ablation of liver malignancies can help predict local tumor progression: initial results. Radiology. 2008;249:364–74.

    Article  PubMed  Google Scholar 

  23. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269–90.

    Article  PubMed  CAS  Google Scholar 

  24. Yang J, Ramnath N, Moysich KB, et al. Prognostic significance of MCM2, Ki-67 and gelsolin in non–small cell lung cancer. BMC Cancer. 2006;6:203.

    Article  PubMed  Google Scholar 

  25. Dodd GD 3rd, Frank MS, Aribandi M, Chopra S, Chintapalli KN. Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations. AJR Am J Roentgenol. 2001;177:777–82.

    PubMed  Google Scholar 

  26. Choi H, Loyer EM, DuBrow RA, et al. Radio-frequency ablation of liver tumors: assessment of therapeutic response and complications. Radiographics. 2001;21(Spec. No.):S41–54.

    Google Scholar 

  27. Goldberg SN, Grassi CJ, Cardella JF, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria. Radiology. 2005 235:728–39.

    Article  PubMed  Google Scholar 

  28. Graur F, Vlad L, Furcea L, Miclaus D, Osian G. Radiofrequency ablation of liver tumors: technique and preliminary results. Chirurgia (Bucur). 2006;101:159–67.

    CAS  Google Scholar 

  29. Curley SA. Radiofrequency ablation of malignant liver tumors. Ann Surg Oncol. 2003;10:338–47.

    Article  PubMed  Google Scholar 

  30. Rossi S, Buscarini E, Garbagnati F, et al. Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol. 1998;170:1015–22.

    PubMed  CAS  Google Scholar 

  31. Solbiati L, Goldberg SN, Ierace T, et al. Hepatic metastases: percutaneous radio-frequency ablation with cooled-tip electrodes. Radiology. 1997;205:367–73.

    PubMed  CAS  Google Scholar 

  32. Pulvirenti A, Garbagnati F, Regalia E, et al. Experience with radiofrequency ablation of small hepatocellular carcinomas before liver transplantation. Transplant Proc. 2001;33:1516–7.

    Article  PubMed  CAS  Google Scholar 

  33. Sofocleous CT, Klein KM, Hubbi B, et al. Histopathologic evaluation of tissue extracted on the radiofrequency probe after ablation of liver tumors: preliminary findings. AJR Am J Roentgenol. 2004;183:209–13.

    PubMed  Google Scholar 

  34. Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol. 2005;23:7212–20.

    Article  PubMed  CAS  Google Scholar 

  35. Tollefson MK, Thompson RH, Sheinin Y, et al. Ki-67 and coagulative tumor necrosis are independent predictors of poor outcome for patients with clear cell renal carcinoma and not surrogates for each other. Cancer. 2007;110:783–90.

    Article  PubMed  Google Scholar 

  36. King KL, Hwang JJ, Chau GY, et al. Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 1998;13:273–9.

    Article  PubMed  CAS  Google Scholar 

  37. Garrity MM, Burgart LJ, Mahoney MR, et al. Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes’ B2 or C colon cancer: a North Central Cancer Treatment Group study. J Clin Oncol. 2004;22:1572–82.

    Article  PubMed  CAS  Google Scholar 

  38. Toquet C, Le Neel JC, Guillou L, et al. Elevated (> or = 10 %) MIB-1 proliferative index correlates with poor outcome in gastric stromal tumor patients: a study of 35 cases. Dig Dis Sci. 2002;47:2247–53.

    Article  PubMed  CAS  Google Scholar 

  39. Vilar E, Salazar R, Pérez-García J, Cortes J, Oberg K, Tabernero J. Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors. Endocr Relat Cancer. 2007;14:221–32.

    Article  PubMed  CAS  Google Scholar 

  40. Weber JC, Nakano H, Bachellier P, et al. Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases? Am J Surg. 2001;182:81–8.

    Article  PubMed  CAS  Google Scholar 

  41. Yu HC, Cheng JS, Lai KH, et al. Factors for early tumor recurrence of single small hepatocellular carcinoma after percutaneous radiofrequency ablation therapy. World J Gastroenterol. 2005;11:1439–44.

    PubMed  Google Scholar 

  42. Snoeren N, Huiskens J, Rijken AM, et al. Viable tumor tissue adherent to needle applicators after local ablation: a risk factor for local tumor progression. Ann Surg Oncol. 2011;18:3702–10.

    Article  PubMed  Google Scholar 

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Acknowledgment

Supported in part by National Institutes of Health grant 5R21CA131763.

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Correspondence to Constantinos T. Sofocleous MD, PhD.

Additional information

Submitted to ASCO Annual Meeting 2011.

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Sofocleous, C.T., Garg, S., Petrovic, L.M. et al. Ki-67 is a Prognostic Biomarker of Survival after Radiofrequency Ablation of Liver Malignancies. Ann Surg Oncol 19, 4262–4269 (2012). https://doi.org/10.1245/s10434-012-2461-9

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  • DOI: https://doi.org/10.1245/s10434-012-2461-9

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