New progress of non-surgical treatments for hepatocellular carcinoma

Medical Oncology

Volumn 30, Issue 1, 2013, Pages

  Cheng, Ji Wen ^a   Lv, Yi ^a  

^a XI'AN JIAOTONG UNIVERSITY   (China)

Author keywords

Hepatocellular carcinoma; Non surgical treatment; Selection internal radiation therapy (SIRT); Systemic chemotherapy; Three dimensional conformal radiotherapy treatment (3 DCRT); Transarterial chemoembolization

Indexed keywords

DENDRITIC CELL VACCINE; FLUOROURACIL; FOLINIC ACID; INTERLEUKIN 2; OXALIPLATIN; SORAFENIB;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER STAGING; CANCER SURVIVAL; CANCER THERAPY; CHEMOEMBOLIZATION; COMPUTER ASSISTED RADIOTHERAPY; CYTOTOXICITY; DISEASE FREE SURVIVAL; EXTERNAL BEAM RADIOTHERAPY; HUMAN; LIVER CELL CARCINOMA; MICROWAVE THERAPY; NONHUMAN; OVERALL SURVIVAL; PRIORITY JOURNAL; RADIOFREQUENCY ABLATION; REVIEW; SUICIDE GENE THERAPY; TUMOR SUPPRESSOR GENE; ABLATION THERAPY; LIVER TUMOR; METHODOLOGY; MULTIMODALITY CANCER THERAPY; RADIOTHERAPY;

ABLATION TECHNIQUES; CARCINOMA, HEPATOCELLULAR; CHEMOEMBOLIZATION, THERAPEUTIC; COMBINED MODALITY THERAPY; HUMANS; LIVER NEOPLASMS; RADIOTHERAPY;

MLCS; MLOWN;

EID: 84880592164     PISSN: 13570560     EISSN: 1559131X     Source Type: Journal    
DOI: 10.1007/s12032-012-0381-y     Document Type: Review

References (97)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917.
2. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-2.
3. Malagari K, Pomoni M, Kelekis A, Pomoni A, Dourakis S, Spyridopoulos T, Moschouris H, Emmanouil E, Rizos S, Kelekis D. Prospective randomized comparison of chemoembolization with doxorubicin eluting beads and bland embolization with Beadblock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010;33(3):541-51.
4. Nicolini A, Martinetti L, Crespi S, Maggioni M, Sangiovanni A. Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21(3):327-32.
5. Malagari K. Drug-eluting particles in the treatment of-HCC: chemoembolization with doxorubicin-loaded DC Bead. Expert Rev Anticancer Ther. 2008;8(10):1643-50.
6. Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, et al. Prospective randomised study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010;33(1):41-52.
7. Vogl TJ, Lammer J, Lencioni R, Malagari K, Watkinson A, Pilleul F, Denys A, Lee C. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011;197(4):W562-70.
8. Muros-Ortega M, Díaz-Carrasco MS, Vila-Clérigues N, Mendoza-Otero F, de la Rubia A, Capel Alemán A. Experience using doxorubicin-loaded DC Beads during hepatic chemoembolisation. Farm Hosp. 2011;35(4):172-9.
9. Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30(1):61-74.
10. Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology. 2010;52(2):762-73.
11. Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M. Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials. Am J Gastroenterol. 2009;104(2):514-24.
12. Germani G, Pleguezuelo M, Gurusamy K, Meyer T, Isgrò G, Burroughs AK. Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic acid injection for hepatocellular carcinoma: a meta-analysis. J Hepatol. 2010;52(3):380-8.
13. Choi D, Lim HK, Rhim H, Kim YS, Lee WJ, Paik SW, Koh KC, Lee JH, Choi MS, Yoo BC. Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment: long-term results and prognostic factors in a large single-institution series. Eur Radiol. 2007;17(3):684-92.
14. 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. 2008;47(1):82-9.
15. Sala M, Llovet JM, Vilana R, Bianchi L, Solé M, Ayuso C, Brú C, Bruix J. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology. 2004;40(6):1352-60.
16. Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129(1):122-30.
17. Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103(6):1201-9.
18. 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. 2008;43(6):727-35.
19. Feng K, Yan J, Li X, Xia F, Ma K, Wang S, Bie P, Dong J. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012;57(4):794-802.
20. Hasegawa K, Makuuchi M, Takayama T, Kokudo N, Arii S, Okazaki M, Okita K, Omata M, Kudo M, Kojiro M, et al. Surgical resection vs. percutaneous ablation for hepatocellular carcinoma; a preliminary report of the Japanese nationwide survey. J Hepatol. 2008;49(4):589-94.
21. Kim H, Rhim H, Choi D, Lim HK, Kim YS, Lee WJ, Joh JW. Recurrence and treatment pattern in long-term survivors with hepatocellular carcinoma: a comparison between radiofrequency ablation and surgery as a first-line treatment. World J Surg. 2010;34(8):1881-6.
22. Song I, Rhim H, Lim HK, Kim YS, Choi D. Percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the diaphragm and gastrointestinal tracts with the use of artificial ascites: safety and technical efficacy in 143 patients. Eur Radiol. 2009;19(11):2630-40.
23. Rhim H, Lim HK, Kim YS, Choi D. Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma in the hepatic dome: initial experience. AJR Am J Roentgenol. 2008;190(1):91-8.
24. Uehara T, Hirooka M, Ishida K, Hiraoka A, Kumagi T, Kisaka Y, Hiasa Y, Onji M. Percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinoma with artificially induced pleural effusion and ascites. J Gastroenterol. 2007;42(4):306-11.
25. Nishimura M, Nouso K, Kariyama K, Wakuta A, Kishida M, Wada N, Higashi T, Yamamoto K. Safety and efficacy of radiofrequency ablation with artificial ascites for hepatocellular carcinoma. Acta Med Okayama. 2012;66(3):279-84.
26. Zhang YJ, Liang HH, Chen MS, Guo RP, Li JQ, Zheng Y, Zhang YQ, Lau WY. Hepatocellular carcinoma treated with radiofrequency ablation with or without ethanol injection: a prospective randomized trial. Radiology. 2007;244(2):599-607.
27. Yamakado K, Nakatsuka A, Takaki H, Yokoi H, Usui M, Sakurai H, Isaji S, Shiraki K, Fuke H, Uemoto S, et al. Early-stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy. Radiology. 2008;247(1):260-6.
28. Yamagiwa K, Shiraki K, Yamakado K, Mizuno S, Hori T, Yagi S, Hamada T, Iida T, Nakamura I, Fujii K, et al. Survival rates according to the cancer of liver Italian Program scores of 345 hepatocellular carcinoma patients after multimodality treatments during a 10-year period in a retrospective study. J Gastroenterol Hepatol. 2008;23(3):482-90.
29. Solazzo SA, Ahmed M, Schor-Bardach R, Yang W, Girnun GD, Rahmanuddin S, Levchenko T, Signoretti S, Spitz DR, Torchilin V, et al. Liposomal doxorubicin increases radiofrequency ablation-induced tumor destruction by increasing cellular oxidative and nitrative stress and accelerating apoptotic pathways. Radiology. 2010;255(1):62-74.
30. Goldberg SN, Kamel IR, Kruskal JB, Reynolds K, Monsky WL, Stuart KE, Ahmed M, Raptopoulos V. Radiofrequency ablation of hepatic tumors: increased tumor destruction with adjuvant liposomal doxorubicin therapy. AJR Am J Roentgenol. 2002;179(1):93-101.
31. Olivo M, Valenza F, Buccellato A, Scala L, Virdone R, Sciarrino E, Di Piazza S, Marrone C, Orlando A, Fusco G, et al. Transcatheter arterial chemoembolisation for hepatocellular carcinoma in cirrhosis: survival rate and prognostic factors. Dig Liver Dis. 2010;42(7):515-9.
32. 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. 2002;35(5):1164-71.
33. Takayasu K, Arii S, Ikai I, Kudo M, Matsuyama Y, Kojiro M, Makuuchi M. Overall survival after transarterial lipiodol infusion chemotherapy with or without embolization for unresectable hepatocellular carcinoma: propensity score analysis. AJR Am J Roentgenol. 2010;194(3):830-7.
34. Bruix J, Llovet JM, Castells A, Montañá X, Brú C, Ayuso MC, Vilana R, Rodés J. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatology. 1998;27(6):1578-83.
35. Pelletier G, Ducreux M, Gay F, Luboinski M, Hagège H, Dao T, Van Steenbergen W, Buffet C, Rougier P, Adler M, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC. J Hepatol. 1998;29(1):129-34.
36. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429-42.
37. Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxì A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224(1):47-54.
38. Malagari K, Chatzimichael K, Alexopoulou E, Kelekis A, Hall B, Dourakis S, Delis S, Gouliamos A, Kelekis D. Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients. Cardiovasc Intervent Radiol. 2008;31(2):269-80.
39. Grosso M, Vignali C, Quaretti P, Nicolini A, Melchiorre F, Gallarato G, Bargellini I, Petruzzi P, Massa Saluzzo C, Crespi S, et al. Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multi-centre study. Cardiovasc Intervent Radiol. 2008;31(6):1141-9.
40. Reyes DK, Vossen JA, Kamel IR, Azad NS, Wahlin TA, Torbenson MS, Choti MA, Geschwind JF. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 2009;15(6):526-32.
41. Seki A, Hori S, Kobayashi K, Narumiya S. Transcatheter arterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for 135 hepatocellular carcinoma patients: single-center experience. Cardiovasc Intervent Radiol. 2011;34(3):557-65.
42. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378-90.
43. Cabibbo G, Enea M, Attanasio M, Bruix J, Craxì A, Cammà C. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology. 2010;51(4):1274-83.
44. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
45. Zhu AX. Systemic treatment of hepatocellular carcinoma: dawn of a new era? Ann Surg Oncol. 2010;17(5):1247-56.
46. Tanaka S, Arii S. Current status of molecularly targeted therapy for hepatocellular carcinoma: basic science. Int J Clin Oncol. 2010;15(3):235-41.
47. Cheng A, Kang Y, Lin D, Park J, Kudo M, Qin S, Omata M, Pitman Lowenthal S W, Lanzalone S, Yang L, et al. Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC). J Clin Oncol 2011; 29 (suppl): 4000 (abstr). Available at: http://www.asco.org/ASCOv2/Meetings/ Abstracts?&vmview=abst-detail-view&confID=102&abstractID=78796.
48. Strumberg D, Clark JW, Awada A, Moore MJ, Richly H, Hendlisz A, Hirte HW, Eder JP, Lenz HJ, Schwartz B. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist. 2007;12(4):426-37.
49. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5(10):835-44.
50. Hampton T. Cancer drug trials show modest benefit: drugs target liver, gastric, head and neck cancers. JAMA. 2007;298(3):273-5.
51. Flaherty KT. Sorafenib: delivering a targeted drug to the right targets. Expert Rev Anticancer Ther. 2007;7(5):617-26.
52. Di Costanzo GG, Tortora R, Iodice L, Lanza AG, Lampasi F, Tartaglione MT, Picciotto FP, Mattera S, De Luca M. Safety and effectiveness of sorafenib in patients with hepatocellular carcinoma in clinical practice. Dig Liver Dis. 2012;44(9):788-92.
53. Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: sub analyses of a phase III trial. J Hepatol. 2012;57(4):821-9.
54. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, 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(1):25-34.
55. Zhang T, Ding X, Wei D, Cheng P, Su X, Liu H, Wang D, Gao H. Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials. Anticancer Drugs. 2010;21(3):326-32.
56. Villanueva A, Llovet JM. Targeted therapies for hepatocellular carcinoma. Gastroenterology. 2011;140(5):1410-26.
57. Zhu AX. Beyond sorafenib: novel targeted therapies for advanced hepatocellular carcinoma. Expert Opin Investig Drugs. 2010;19(5):663-72.
58. Rimassa L, Santoro A. The present and the future landscape of treatment of advanced hepatocellular carcinoma. Dig Liver Dis. 2010;42(Suppl 3):S273-80.
59. Wörns MA, Schuchmann M, Düber C, Otto G, Galle PR, Weinmann A. Sunitinib in patients with advanced hepatocellular carcinoma after progression under sorafenib treatment. Oncology. 2010;79(1-2):85-92.
60. Dawson LA, Ten Haken RK, Lawrence TS. Partial irradiation of the liver. Semin Radiat Oncol. 2001;11(3):240-6.
61. Liu MT, Li SH, Chu TC, Hsieh CY, Wang AY, Chang TH, Pi CP, Huang CC, Lin JP. Three-dimensional conformal radiation therapy for unresectable hepatocellular carcinoma patients who had failed with or were unsuited for transcatheter arterial chemoembolization. Jpn J Clin Oncol. 2004;34(9):532-9.
62. 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. 2006;29(6):568-75.
63. Ohto M, Yoshikawa M, Saisho H, Ebara M, Sugiura N. Nonsurgical treatment of hepatocellular carcinoma in cirrhotic patients. World J Surg. 1995;19(1):42-6.
64. Shirai S, Sato M, Suwa K, Kishi K, Shimono C, Kawai N, Tanihata H, Minamiguchi H, Nakai M. Single photon emission computed tomography-based three-dimensional conformal radiotherapy for three-dimensional conformal radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus. Int J Radiat Oncol Biol Phys. 2009;73(3):824-31.
65. Zhao JD, Xu ZY, Zhu J, Qiu JJ, Hu WG, Cheng LF, Zhang XJ, Jiang GL. Application of active breathing control in 3-dimensional conformal radiation therapy for hepatocellular carcinoma: the feasibility and benefit. Radiother Oncol. 2008;87(3):439-44.
66. Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, Heusner T, Cicinnati VR, Paul A, Bockisch A, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52(5):1741-9.
67. Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138(1):52-64.
68. Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54(3):868-78.
69. Han KH, Seong J, Kim JK, Ahn SH. Lee do Y, Chon CY. Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer. 2008;113(5):995-1003.
70. Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, Sato KT, Gupta R, Nikolaidis P, Miller FH, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011; 140(2):497-507.
71. Iñarrairaegui M, Thurston KG, Bilbao JI, D'Avola D, Rodriguez M, Arbizu J, Martinez-Cuesta A, Sangro B. Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol. 2010;21(8):1205-12.
72. Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchianò A, Bongini M, Lanocita R, et al. Yttrium(90) radioembolization for intermediate-advanced hepatocarcinoma: a phase II study. Hepatology. 2012;. doi: 10.1002/hep.26014.
73. Palmer DH, Hussain SA, Johnson PJ. Systemic therapies for hepatocellular carcinoma. Expert Opin Investig Drugs. 2004;13(12):1555-68.
74. Ang MK, Poon D, Foo KF, Chung YF, Chow P, Wan WK, Thng CH, Ooi L. A new chemoimmunotherapy regimen (OXAFI) for advanced hepatocellular carcinoma. Hematol Oncol Stem Cell Ther. 2008;1(3):159-65.
75. Uhm JE, Park JO, Lee J, Park YS, Park SH, Yoo BC, Paik SW, Koh KC, Kang WK, Lim HY. A phase II study of oxaliplatin in combination with doxorubicin as first-line systemic chemotherapy in patients with inoperable hepatocellular carcinoma. Cancer Chemother Pharmacol. 2009;63(5):929-35.
76. Zaanan A, Williet N, Hebbar M, Dabakuyo TS, Fartoux L, Mansourbakht T, Dubreuil O, Rosmorduc O, Cattan S, Bonnetain F, et al. Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large multicenter AGEO study. J Hepatol. 2012. doi: 10.1016/j.jhep.2012.09.006.
77. Qin S, Bai Y, Ye S, Fan J, Lim H, Cho JY, Thongprasert S, Chao Y, Rau K, Sun Y. Phase III study of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) versus doxorubicin as palliative systemic chemotherapy in advanced HCC in Asian patients. J Clin Oncol 28:15 s, 2010 (suppl; abstr 4008). Available at: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst-detail- view&confID=74&abstractID=42222.
78. Petrini I, Lencioni M, Ricasoli M, Iannopollo M, Orlandini C, Oliveri F, Bartolozzi C, Ricci S. Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2012;69(3):773-80.
79. Strebel BM, Dufour JF. Combined approach to hepatocellular carcinoma: a new treatment concept for nonresectable disease. Expert Rev Anticancer Ther. 2008;8(11):1743-9.
80. ClinicalTrials. Chemoembolization with or without sorafenib tosylate in treating patients with liver cancer that cannot be removed by surgery. Last Updated on Sept 12, 2012. Available at: http://clinicaltrials.gov/ct2/show/ NCT01004978 ?.
81. Meyer T, Fox R, Bird D, Watkinson A, Hacking N, Stocken D, Johnson PJ, Palmer DH. TACE 2: a randomized placebo-controlled, double blinded, phase III trial evaluating sorafenib in combination with transarterial chemoembolisation(TACE) in patients with unresectable hepatocellular carcinoma (HCC). J Clin Oncol 30, 2012 (suppl; abstr TPS4150). Available at: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst-detail- view&confID=114&abstractID=96699.
82. Lencioni R, Zou J, Leberre M, Meinhardt G, Voliotis D, Bruix J, Llovet JM. Sorafenib (SOR) or placebo (PL) in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (SPACE).J Clin Oncol 28:15s, 2010 (suppl; abstr TPS178). Available at: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst-detail- view&confID=74&abstractID=43588.
83. Gadaleta CD, Ranieri G. Trans-arterial chemoembolization as a therapy for liver tumours: new clinical developments and suggestions for combination with angiogenesis inhibitors. Crit Rev Oncol Hematol. 2011;80(1):40-53.
84. Park JW, Koh YH, Kim HB, Kim HY, An S, Choi JI, Woo SM, Nam BH. Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatol. 2012;56(6):1336-42.
85. Merle P, Mornex F, Trepo C. Innovative therapy for hepatocellular carcinoma: three-dimensional high-dose photon radiotherapy. Cancer Lett. 2009;286(1):129-33.
86. Reiser M, Neumann I, Schmiegel W, Wu PC, Lau JY. Induction of cell proliferation arrest and apoptosis in hepatoma cells through adenoviral-mediated transfer of p53 gene. J Hepatol. 2000;32(5):771-82.
87. Guan YS, La Z, Yang L, He Q, Li P. p53 gene in treatment of hepatic carcinoma: status quo. World J Gastroenterol. 2007;13(7):985-92.
88. Martinet O, Ermekova V, Qiao JQ, Sauter B, Mandeli J, Chen L, Chen SH. Immunomodulatory gene therapy with interleukin 12 and 4-1BB ligand: long- term remission of liver metastases in a mouse model. J Natl Cancer Inst. 2000;92(11):931-6.
89. Yang W, Guo C, Liu QG, Pan C. Experimental study of specific immunotherapy induced by H22 autologous tumor as whole tumor cell vaccine. Biomed Pharmacother. 2009;63(6):404-8.
90. Los M, Panigrahi S, Rashedi I, Mandal S, Stetefeld J, Essmann F, Schulze-Osthoff K. Apoptin, a tumor-selective killer. Biochim Biophys Acta. 2009;1793(8):1335-42.
91. Zhang KJ, Qian J, Wang SB, Yang Y. Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma. J Biomed Sci. 2012;19:20.
92. Bertelli R, Neri F, Tsivian M, Ruhrman N, Cavallari G, Beltempo P, Puviani L, DeVinci C, Pizza G, Nardo B. Endolymphatic immunotherapy in inoperable hepatocellular carcinoma. Transplant Proc. 2008;40(6):1913-5.
93. Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006;132(7):458-65.
94. Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, Fan ST, Wong J. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg. 2007;245(6):831-42.
95. Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, Capussotti L, Calise F, Pellicci R, Belli G, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44(6):1543-54.
96. Palmer DH, Midgley RS, Mirza N, Torr EE, Ahmed F, Steele JC, Steven NM, Kerr DJ, Young LS, Adams DH. A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology. 2009;49(1):124-32.
97. Shimoda M, Tomimaru Y, Charpentier KP, Safran H, Carlson RI, Wands J. Tumor progression-related transmembrane protein aspartate-β-hydroxylase is a target for immunotherapy of hepatocellular carcinoma. J Hepatol. 2012;56(5):1129-35.