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01-12-2012 | Hepatobiliary Tumors

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

Authors: Constantinos T. Sofocleous, MD, PhD, Sandeep Garg, MS, Lydia M. Petrovic, MD, PhD, Mithat Gonen, PhD, Elena N. Petre, MD, David S. Klimstra, MD, Stephen B. Solomon, MD, Karen T. Brown, MD, Lynn A. Brody, MD, Ann M. Covey, MD, Ronald P. DeMatteo, MD, Lawrence Schwartz, MD, Nancy E. Kemeny, MD

Published in: Annals of Surgical Oncology | Issue 13/2012

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.

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

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.CrossRef

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

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

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

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

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.CrossRef

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.PubMedCrossRef

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

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.PubMedCrossRef

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.PubMedCrossRef

12.

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

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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

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.

27.

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

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.

29.

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

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

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

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.PubMedCrossRef

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

34.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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

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.PubMedCrossRef

Title: Ki-67 is a Prognostic Biomarker of Survival after Radiofrequency Ablation of Liver Malignancies
Authors: Constantinos T. Sofocleous, MD, PhD
Sandeep Garg, MS
Lydia M. Petrovic, MD, PhD
Mithat Gonen, PhD
Elena N. Petre, MD
David S. Klimstra, MD
Stephen B. Solomon, MD
Karen T. Brown, MD
Lynn A. Brody, MD
Ann M. Covey, MD
Ronald P. DeMatteo, MD
Lawrence Schwartz, MD
Nancy E. Kemeny, MD
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 13/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2461-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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