Advances in the treatment of hepatocellular carcinoma

간세포암종 치료의 최신 지견

Lee, June-Sung
이준성

  • Published : 20090900

Abstract

There have been recent advances in the treatment of hepatocellular carcinoma (HCC). There has been a clear change in the presentation of HCC, with an increased detection of tumors <2 cm in diameter as result of surveillance programs. In addition, the development of effective local treatment methods has led to the necessity for the selection of base therapeutic modalities on each patient's characteristics. New promising image-guided therapies and new drugs, such as sorafenib, may address the enormous need for expanded treatment options for patients with HCC. Tailored therapies are needed to improve the treatment response and, ultimately, patient survival. Here, we review these advances in the management of HCC.

Keywords

References

  1. Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, Rossi S. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology 47:82-89, 2008 https://doi.org/10.1002/hep.21933
  2. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434-1440, 1999 https://doi.org/10.1002/hep.510300629
  3. Zhou XD, Tang ZY, Yang BH, Lin ZY, Ma ZC, Ye SL, Wu ZQ, Fan J, Qin LX, Zheng BH. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma. Cancer 91:1479-1486, 2001 https://doi.org/10.1002/1097-0142(20010415)91:8<1479::AID-CNCR1155>3.0.CO;2-0
  4. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, Curley SA, Ellis LM, Regimbeau JM, Rashid A, Cleary KR, Nagorney DM. Simplified staging for hepatocellular carcinoma. J Clin Oncol 20:1527-1536, 2002 https://doi.org/10.1200/JCO.20.6.1527
  5. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235:373-382, 2002 https://doi.org/10.1097/00000658-200203000-00009
  6. Kumada T, Nakano S, Takeda I, Sugiyama K, Osada T, Kiriyama S, Sone Y, Toyoda H, Shimada S, Takahashi M, Sassa T. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma. Hepatology 25:87-92, 1997 https://doi.org/10.1002/hep.510250116
  7. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, Minagawa M, Takayama T, Kawasaki S, Makuuchi M. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 38:200-207, 2003
  8. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25: 181-200, 2005 https://doi.org/10.1055/s-2005-871198
  9. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693-699, 1996 https://doi.org/10.1056/NEJM199603143341104
  10. Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 19:311-322, 1999 https://doi.org/10.1055/s-2007-1007120
  11. Roayaie S, Frischer JS, Emre SH, Fishbein TM, Sheiner PA, Sung M, Miller CM, Schwartz ME. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg 235:533-539, 2002 https://doi.org/10.1097/00000658-200204000-00012
  12. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 42:1208-1236, 2005 https://doi.org/10.1002/hep.20933
  13. Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M, Makuuchi M, Nakamura Y, Okita K, Yamada R. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology 32:1224-1229, 2000 https://doi.org/10.1053/jhep.2000.20456
  14. Beaugrand M, N'Kontchou G, Seror O, Ganne N, Trinchet JC. Local/regional and systemic treatments of hepatocellular carcinoma. Semin Liver Dis 25:201-211, 2005 https://doi.org/10.1055/s-2005-871199
  15. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio- frequency ablation versus ethanol injection. Radiology 210:655-661, 1999 https://doi.org/10.1148/radiology.210.3.r99fe40655
  16. Lencioni RA, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, Frings H, Laubenberger J, Zuber I, Blum HE, Bartolozzi C. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228:235-240, 2003 https://doi.org/10.1148/radiol.2281020718
  17. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology 127: 1714-1723, 2004 https://doi.org/10.1053/j.gastro.2004.09.003
  18. Rhim H, Yoon KH, Lee JM, Cho Y, Cho JS, Kim SH, Lee WJ, Lim HK, Nam GJ, Han SS, Kim YH, Park CM, Kim PN, Byun JY. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics 23:123-134; discussion 134-136, 2003 https://doi.org/10.1148/rg.231025054
  19. de Baere T, Risse O, Kuoch V, Dromain C, Sengel C, Smayra T, Gamal El Din M, Letoublon C, Elias D. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol 181:695-700, 2003 https://doi.org/10.2214/ajr.181.3.1810695
  20. Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243:321-328, 2006 https://doi.org/10.1097/01.sla.0000201480.65519.b8
  21. Hong SN, Lee SY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC, Rhee JC, Choi D, Lim HK, Lee KW, Joh JW. Comparing the outcomes of radiofrequency ablation and surgery in patients with a single small hepatocellular carcinoma and well-preserved hepatic function. J Clin Gastroenterol 39:247-252, 2005 https://doi.org/10.1097/01.mcg.0000152746.72149.31
  22. Lupo L, Panzera P, Giannelli G, Memeo M, Gentile A, Memeo V. Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation or resection? HPB (Oxford) 9:429-434, 2007
  23. Abu-Hilal M, Primrose JN, Casaril A, McPhail MJ, Pearce NW, Nicoli N. Surgical resection versus radiofrequency ablation in the treatment of small unifocal hepatocellular carcinoma. J Gastrointest Surg 12:1521-1526, 2008 https://doi.org/10.1007/s11605-008-0553-4
  24. Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242:36-42, 2005 https://doi.org/10.1097/01.sla.0000167925.90380.fe
  25. Gournay J, Tchuenbou J, Richou C, Masliah C, Lerat F, Dupas B, Martin T, Nouel JF, Schnee M, Montigny P, D'Alincourt A, Hamy A, Paineau J, Le Neel JC, Le Borgne J, Galmiche JP. Percutaneous ethanol injection vs. resection in patients with small single hepatocellular carcinoma: a retrospective case-control study with cost analysis. Aliment Pharmacol Ther 16:1529-1538, 2002 https://doi.org/10.1046/j.1365-2036.2002.01307.x
  26. Daniele B, De Sio I, Izzo F, Capuano G, Andreana A, Mazzanti R, Aiello A, Vallone P, Fiore F, Gaeta GB, Perrone F, Pignata S, Gallo C. Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma: a Cancer of the Liver Italian Program (CLIP 08) retrospective case-control study. J Clin Gastroenterol 36:63-67, 2003 https://doi.org/10.1097/00004836-200301000-00017
  27. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54:1151-1156, 2005 https://doi.org/10.1136/gut.2004.045203
  28. Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, Omata M. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129:122-130, 2005 https://doi.org/10.1053/j.gastro.2005.04.009
  29. Brunello F, Veltri A, Carucci P, Pagano E, Ciccone G, Moretto P, Sacchetto P, Gandini G, Rizzetto M. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: a randomized controlled trial. Scand J Gastroenterol 43:727-735, 2008 https://doi.org/10.1080/00365520701885481
  30. Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 49:453-459, 2009 https://doi.org/10.1002/hep.22648
  31. Matsui O, Kadoya M, Yoshikawa J, Gabata T, Takashima T, Demachi H. Subsegmental transcatheter arterial embolization for small hepatocellular carcinomas: local therapeutic effect and 5-year survival rate. Cancer Chemother Pharmacol 33(Suppl): S84-S88, 1994 https://doi.org/10.1007/BF00686674
  32. Miyayama S, Matsui O, Yamashiro M, Ryu Y, Kaito K, Ozaki K, Takeda T, Yoneda N, Notsumata K, Toya D, Tanaka N, Mitsui T. Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas: relationship between local tumor recurrence and visualization of the portal vein with iodized oil. J Vasc Interv Radiol 18:365-376, 2007 https://doi.org/10.1016/j.jvir.2006.12.004
  33. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734-1739, 2002 https://doi.org/10.1016/S0140-6736(02)08649-X
  34. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164-1171, 2002 https://doi.org/10.1053/jhep.2002.33156
  35. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429-442, 2003 https://doi.org/10.1053/jhep.2003.50047
  36. Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224: 47-54, 2002 https://doi.org/10.1148/radiol.2241011262
  37. Lee HS, Kim KM, Yoon JH, Lee TR, Suh KS, Lee KU, Chung JW, Park JH, Kim CY. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol 20:4459-4465, 2002 https://doi.org/10.1200/JCO.2002.02.013
  38. Cheng BQ, Jia CQ, Liu CT, Fan W, Wang QL, Zhang ZL, Yi CH. Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. JAMA 299:1669-1677, 2008 https://doi.org/10.1001/jama.299.14.1669
  39. Chlebowski RT, Brzechwa-Adjukiewicz A, Cowden A, Block JB, Tong M, Chan KK. Doxorubicin (75 mg/m2) for hepatocellular carcinoma: clinical and pharmacokinetic results. Cancer Treat Rep 68:487-491, 1984
  40. Falkson G, MacIntyre JM, Moertel CG, Johnson LA, Scherman RC. Primary liver cancer: an Eastern Cooperative Oncology Group Trial. Cancer 54:970-977, 1984 https://doi.org/10.1002/1097-0142(19840915)54:6<970::AID-CNCR2820540604>3.0.CO;2-7
  41. Melia WM, Johnson PJ, Williams R. Induction of remission in hepatocellular carcinoma: a comparison of VP 16 with adriamycin. Cancer 51:206-210, 1983 https://doi.org/10.1002/1097-0142(19830115)51:2<206::AID-CNCR2820510206>3.0.CO;2-P
  42. Falkson G, Ryan LM, Johnson LA, Simson IW, Coetzer BJ, Carbone PP, Creech RH, Schutt AJ. A random phase II study of mitoxantrone and cisplatin in patients with hepatocellular carcinoma: an ECOG study. Cancer 60:2141-2145, 1987 https://doi.org/10.1002/1097-0142(19871101)60:9<2141::AID-CNCR2820600903>3.0.CO;2-4
  43. Patt YZ, Hassan MM, Lozano RD, Brown TD, Vauthey JN, Curley SA, Ellis LM. Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol 21:421-427, 2003 https://doi.org/10.1200/JCO.2003.10.103
  44. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099-7109, 2004 https://doi.org/10.1158/0008-5472.CAN-04-1443
  45. Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, Wilkie D, Carter CA, Taylor IC, Lynch M, Wilhelm S. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59:561-574, 2007 https://doi.org/10.1007/s00280-006-0393-4
  46. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 59:378-390, 2008 https://doi.org/10.1056/NEJMoa0708857
  47. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. 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 10:25-34, 2009 https://doi.org/10.1016/S1470-2045(08)70285-7
  48. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293-4300, 2006 https://doi.org/10.1200/JCO.2005.01.3441
  49. Park W, Lim DH, Paik SW, Koh KC, Choi MS, Park CK, Yoo BC, Lee JE, Kang MK, Park YJ, Nam HR, Ahn YC, Huh SJ. Local radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 61:1143-1150, 2005 https://doi.org/10.1016/j.ijrobp.2004.08.028
  50. Kim TH, Kim DY, Park JW, Kim YI, Kim SH, Park HS, Lee WJ, Park SJ, Hong EK, Kim CM. Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable. Am J Clin Oncol 29:568-575, 2006 https://doi.org/10.1097/01.coc.0000239147.60196.11
  51. Seong J, Lee IJ, Shim SJ, Lim do H, Kim TH, Kim JH, Jang HS, Kim MS, Chie EK, Nam TK, Lee HS, Han CJ. A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea. Liver Int 29:147-152, 2009 https://doi.org/10.1111/j.1478-3231.2008.01873.x
  52. Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48(Suppl 1):S20- S37, 2008