Efficacy and safety of transarterial chemoembolization combined to conformal radiotherapy for uninodular hepatocellular carcinoma
Purpose: A proportion of patients with uninodular hepatocellular carcinoma (HCC) cannot benefit from potential curative therapies such as liver transplantation, surgical resection or radiofrequency ablation. Thus, they are prone to receive transarterial chemoembolization (TACE) that is a palliative option with low probability of both complete response and prolonged local control. Herein, we assessed the combination of TACE and 3D-high dose conformal radiotherapy (3D-HDCRT) for efficacy and safety in HCC.
Methods: We retrospectively analyzed the outcome of 35 consecutive patients with uninodular HCC ≤ 100 mm, treated by one course of TACE combined to 3D-HDCRT. The follow-up consisted on clinics, biology, hepatic CT-scan or MRI at month-1 and -3, and thereafter every 3 months.
Results: Complete response was obtained in 80% of patients following mRECIST criteria (95% in HCC ≤ 50 mm, and 60% in HCC > 50 mm) with uncommon local recurrence (11%), overall survival rates of 79%, 59% and 44% at respectively 1, 2 and 3 years (median, 37.3 months), and 11.4% grade-3/4 toxicities. Pre-therapeutic α-fetoprotein level ≥ 200 ng/mL was found as a strong predictor of poorer outcome.
Conclusion: We showed that TACE combined to 3D-HDCRT can be highly efficient to reach local control and interesting overall survival rates for uninodular HCC, with limited severe toxicities for Child-Pugh A patients. Subsequent prospective controlled trials are warranted for comparison with therapeutic standards.
El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340:745-50.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005; 55:74-108.
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53:1020-2.
Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolisation for unresectable hepatocellular carcinoma. Hepatology 2002; 35:1164-71.
Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002; 359:1734-9.
Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology 2004; 127:S179-88.
Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005; 42:1208-36.
Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362:1907-17.
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003; 37:429-42.
Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005; 25:181-200.
Seong J, Keum KC, Han KH, et al. Combined transcathter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 1999; 43:393-7.
Guo WJ, Yu EX. Evaluation of combined therapy with chemoembolization and irradiation for large hepatocellular carcinoma. B J Radiol 2000; 73:1091-7.
Guo WJ, Yu EX, Liu LM, et al. Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma. World J Gastroenterol 2003; 9:1697-701.
Shim SJ, Seong J, Han KH, et al. Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma. Liver Int 2005; 25:1189-96.
Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008; 100:698-711.
Ten Haken RK, Lawrence TS, McShan DL, et al. Technical considerations in the use of 3-D beam arrangements in the abdomen. Radiother Oncol 1991; 22:19-28.
Dawson LA, Brock KK, Kazanjian S, et al. The reproducibility of organ position using active breathing control (ABC) during liver radiotherapy. Int J Radiat Oncol Biol Phys 2001; 51:1410-21.
Mornex F, Girard N, Beziat C, et al. Feasibility and efficacy of high-dose three-dimensional-conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma noneligible for curative therapies – Mature results of the French phase 2 RTF-1 trial. Int J Radiat Oncol Biol Phys 2006; 66:1152-8.
Lawrence TS, Tesser RJ, ten Haken RK. An application of dose volume histograms to the treatment of intrahepatic malignancies with radiation therapy. Int J Radiat Oncol Biol Phys 1990; 19:1041-7.
Lawrence TS, Ten Haken RK, Kessler ML, et al. The use of 3-D dose volume analysis to predict radiation hepatitis. Int J Radiat Oncol Biol Phys 1992; 23:781-8.
McGinn CJ, Ten Haken RK, Ensminger WD, et al. Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model. J Clin Oncol 1998; 16:2246-52.
Late Effects of Normal Tissues (LENT) Consensus Conference. LENT SOMA scales for all anatomic sites. Int J Radiat Oncol Biol Phys 1995; 31:1049-91.
Merle P, Mornex F, Trepo C. Innovative therapy for hepatocellular carcinoma: three-dimensional high-dose photon radiotherapy. Cancer Lett 2009; 286:129-33.
Dawson LA. Where does radiation therapy fit in the spectrum of liver cancer local-regional therapies? Semin Radiat Oncol 2011; 21:241-6.
Xiong ZP, Yang SR, Liang ZY, et al. Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2004; 3:386-90.
Cheng JC, Chuang VP, Cheng SH, et al. Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol 2000; 47:435-42.
Chia-Hsien Cheng J, Chuang VP, Cheng SH, et al. Unresectable hepatocellular carcinoma treated with radiotherapy and/or chemoembolization. Int J Cancer 2001; 96:243-52.
Seong J, Park HC, Han KH, et al. Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients. Hepatology Research 2003; 27:30-5.
Khan MR, Poon RTP, Ng KK, et al. Comparison of percutaneous and surgical approaches for radiofrequency ablation of small and medium hepatocellular carcinoma. Arch Surg 2007; 142:1136-43.
Nagasue N, Kohno H, Chang YC, et al. Liver resection for hepatocellular carcinoma. Results of 229 consecutive patients during 11 years. Ann Surg 1993; 217:375-84.
Kotoh K, Sakai H, Sakamoto S, et al. The effect of percutaneous ethanol injection therapy on small solitary hepatocellular carcinoma is comparable to that of hepatectomy. Am J Gastroenterol 1994; 89:194-8.
Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334:693-9.
Izumi R, Shimizu K, Iyobe T, et al. Postoperative adjuvant hepatic arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology 1994; 20:295-301.
Fong Y, Sun RL, Jarnagin W, Blumgart LH. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 1999; 229:790-9.
Curley SA, Izzo F, Ellis LM, et al. Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 2000; 232:381-91.
Decadt B, Sirlwardena AK. Radiofrequency ablation of liver tumors: Systematic review. Lancet Oncol 2004; 5:550-60.
Delis SG, Bakoyiannis A, Tassopoulos N, et al. Hepatic resection for hepatocellular carcinoma exceeding Milan criteria. Surg Oncol 2010; 19:200-7.
Schiffman SC, Woodall CE, Kooby DA, et al. Factors associated with recurrence and survival following hepatectomy for large hepatocellular carcinoma: a multicenter analysis. J Surg Oncol 2010; 101:105-10.
Wu DH, Liu L, Chen LH. Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol 2004; 10:2184-9.
Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer 2006; 106:1653-63.
Jang WI, Kim MS, Bae SH, et al. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiat Oncol 2013; 8:250-61.
Jung J, Yoon SM, Kim SY, et al. Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters. Radiat Oncol 2013; 8:249-55
This work is licensed under a Creative Commons Attribution 3.0 License.
International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)
© International Journal of Cancer Therapy and Oncology (IJCTO)
To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.