Hepatocellular carcinoma review: Current treatment, and evidence-based medicine

World Journal of Gastroenterology

Volumn 20, Issue 15, 2014, Pages 4115-4127

  Raza, Ali ^a   Sood, Gagan K ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Chemotherapy; Drug eluting beads; Hepatocellular carcinoma; Liver transplantation; Radioembolization; Radiofrequency ablation; Sorafenib; Trans arterial chemoembolization

Indexed keywords

BRIVANIB; CISPLATIN; DOXORUBICIN; ERLOTINIB; GEMCITABINE; IODINATED POPPYSEED OIL; LINIFANIB; MITOMYCIN; OCTREOTIDE; OXALIPLATIN; SORAFENIB; SUNITINIB; TIVANTINIB; UFT; CARBANILAMIDE DERIVATIVE; NICOTINAMIDE;

ANGIOGENESIS; ARTICLE; ARTIFICIAL EMBOLISM; CANCER STAGING; DISEASE COURSE; EVIDENCE BASED MEDICINE; HUMAN; LIVER CELL CARCINOMA; LIVER FUNCTION; LIVER TRANSPLANTATION; META ANALYSIS (TOPIC); PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PORTAL HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); TUMOR RECURRENCE; TUMOR VOLUME; ANALOGS AND DERIVATIVES; CARCINOMA, HEPATOCELLULAR; CATHETER ABLATION; CHEMOEMBOLIZATION; CLINICAL TRIAL (TOPIC); LIVER NEOPLASMS; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; PROCEDURES; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

CARCINOMA, HEPATOCELLULAR; CATHETER ABLATION; CHEMOEMBOLIZATION, THERAPEUTIC; CLINICAL TRIALS AS TOPIC; COMBINED MODALITY THERAPY; EVIDENCE-BASED MEDICINE; HUMANS; LIVER NEOPLASMS; LIVER TRANSPLANTATION; MOLECULAR TARGETED THERAPY; NIACINAMIDE; PHENYLUREA COMPOUNDS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84898871130     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i15.4115     Document Type: Article

References (110)

1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142: 1264-1273. e1 [PMID: 22537432 DOI: 10.1053/j.gastro.2011.12.061]
2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379: 1245-1255 [PMID: 22353262 DOI: 10.1016/ S0140-6736(11)61347-0]
3. Marrero JA. Current Treatment Approaches in HCC. Clin Adv Hematol Oncol 2013; 11 Suppl 5: 15-18
4. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022 [PMID: 21374666 DOI: 10.1002/hep.24199]
5. European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer. EASLEORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56: 908-943 [PMID: 22424438 DOI: 10.1016/j.jhep.2011.12.001]
6. Lencioni R, Chen XP, Dagher L, Venook AP. Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved? Oncologist 2010; 15 Suppl 4: 42-52 [PMID: 21115580 DOI: 10.1634/theoncologist. 2010-S4-42]
7. 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 1996; 334: 693-699 [PMID: 8594428 DOI: 10.1056/NEJM199603143341104]
8. Mazzaferro V. Results of liver transplantation: with or with-out Milan criteria? Liver Transpl 2007; 13: S44-S47 [PMID: 17969068 DOI: 10.1002/lt.21330]
9. Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, Mariani L. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl 2011; 17 Suppl 2: S44-S57 [PMID: 21695773 DOI: 10.1002/lt.22365]
10. Taniguchi M. Liver transplantation in the MELD era--analysis of the OPTN/UNOS registry. Clin Transpl 2012; 41-65 [PMID: 23721009]
11. Prasad KR, Young RS, Burra P, Zheng SS, Mazzaferro V, Moon DB, Freeman RB. Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: a review and consensus statement. Liver Transpl 2011; 17 Suppl 2: S81-S89 [PMID: 21748847 DOI: 10.1002/ lt.22380]
12. Washburn K, Halff G. Hepatocellular carcinoma and liver transplantation. Curr Opin Organ Transplant 2011; 16: 297-300 [PMID: 21505342 DOI: 10.1097/MOT.0b013e3283465756]
13. Gordon-Weeks AN, Snaith A, Petrinic T, Friend PJ, Burls A, Silva MA. Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg 2011; 98: 1201-1208 [PMID: 21618496 DOI: 10.1002/bjs.7561]
14. Cescon M, Cucchetti A, Ravaioli M, Pinna AD. Hepatocellular carcinoma locoregional therapies for patients in the waiting list. Impact on transplantability and recurrence rate. J Hepatol 2013; 58: 609-618 [PMID: 23041304 DOI: 10.1016/ j.jhep.2012.09.021]
15. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, De Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, Van Hoek B, Majno P. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10: 35-43 [PMID: 19058754 DOI: 10.1016/ S1470-2045(08)70284-5]
16. Cucchetti A, Cescon M, Bigonzi E, Piscaglia F, Golfieri R, Ercolani G, Cristina Morelli M, Ravaioli M, Daniele Pinna A. Priority of candidates with hepatocellular carcinoma awaiting liver transplantation can be reduced after successful bridge therapy. Liver Transpl 2011; 17: 1344-1354 [PMID: 21837731 DOI: 10.1002/lt.22397]
17. Yao FY, Kerlan RK, Hirose R, Davern TJ, Bass NM, Feng S, Peters M, Terrault N, Freise CE, Ascher NL, Roberts JP. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 2008; 48: 819-827 [PMID: 18688876 DOI: 10.1002/hep.22412]
18. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13: e11-e22 [PMID: 22047762 DOI: 10.1016/S1470-2045(11)70175-9]
19. Vitale A, Volk ML, De Feo TM, Burra P, Frigo AC, Ramirez Morales R, De Carlis L, Belli L, Colledan M, Fagiuoli S, Rossi G, Andorno E, Baccarani U, Regalia E, Vivarelli M, Donataccio M, Cillo U. A method for establishing allocation equity among patients with and without hepatocellular carcinoma on a common liver transplant waiting list. J Hepatol 2014; 60: 290-297 [PMID: 24161408 DOI: 10.1016/j.jhep.2013.10.010]
20. Volk ML, Vijan S, Marrero JA. A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant 2008; 8: 839-846 [PMID: 18318783 DOI: 10.1111/j.1600-6143.2007.02138.x]
21. Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G, Vivarelli M, Golfieri R, D'Errico Grigioni A, Panzini I, Morelli C, Bernardi M, Bolondi L, Pinna AD. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 2008; 8: 2547-2557 [PMID: 19032223 DOI: 10.1111/j.1600-6143.2008.02409.x]
22. Schwartz M, Dvorchik I, Roayaie S, Fiel MI, Finkelstein S, Marsh JW, Martignetti JA, Llovet JM. Liver transplantation for hepatocellular carcinoma: extension of indications based on molecular markers. J Hepatol 2008; 49: 581-588 [PMID: 18602719 DOI: 10.1016/j.jhep.2008.03.032]
23. Bhoori S, Schiavo M, Russo A, Mazzaferro V. First-line treatment for hepatocellular carcinoma: resection or transplantation? Transplant Proc 2007; 39: 2271-2273 [PMID: 17889160 DOI: 10.1016/j.transproceed.2007.06.015]
24. Beard RE, Hanto DW, Gautam S, Miksad RA. A comparison of surgical outcomes for noncirrhotic and cirrhotic hepatocellular carcinoma patients in a Western institution. Surgery 2013; 154: 545-555 [PMID: 23777589 DOI: 10.1016/ j.surg.2013.02.019]
25. Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC, Visa J, Bru C, Rodés J. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 1996; 111: 1018-1022 [PMID: 8831597 DOI: 10.1016/S0016-5085(96)70070-7]
26. Ruzzenente A, Valdegamberi A, Campagnaro T, Conci S, Pachera S, Iacono C, Guglielmi A. Hepatocellular carcinoma in cirrhotic patients with portal hypertension: is liver resection always contraindicated? World J Gastroenterol 2011; 17: 5083-5088 [PMID: 22171142 DOI: 10.3748/wjg.v17.i46.5083]
27. Kawano Y, Sasaki A, Kai S, Endo Y, Iwaki K, Uchida H, Shibata K, Ohta M, Kitano S. Short-and long-term outcomes after hepatic resection for hepatocellular carcinoma with concomitant esophageal varices in patients with cirrhosis. Ann Surg Oncol 2008; 15: 1670-1676 [PMID: 18368453 DOI: 10.1245/s10434-008-9880-7]
28. Cucchetti A, Ercolani G, Vivarelli M, Cescon M, Ravaioli M, Ramacciato G, Grazi GL, Pinna AD. Is portal hypertension a contraindication to hepatic resection? Ann Surg 2009; 250: 922-928 [PMID: 19855258 DOI: 10.1097/SLA.0b013e3181b977a5]
29. Santambrogio R, Kluger MD, Costa M, Belli A, Barabino M, Laurent A, Opocher E, Azoulay D, Cherqui D. Hepatic resection for hepatocellular carcinoma in patients with Child-Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB (Oxford) 2013; 15: 78-84 [PMID: 23216782 DOI: 10.1111/j.1477-2574.2012.00594.x]
30. Barbier L, Fuks D, Pessaux P, Muscari F, Le Treut YP, Faivre S, Belghiti J. Safety of liver resection for hepatocellular carcinoma after sorafenib therapy: a multicenter case-matched study. Ann Surg Oncol 2013; 20: 3603-3609 [PMID: 23715965 DOI: 10.1245/s10434-013-3029-z]
31. Wong TC, Lo CM. Resection strategies for hepatocellular carcinoma. Semin Liver Dis 2013; 33: 273-281 [PMID: 23943107 DOI: 10.1055/s-0033-1351782]
32. Cucchetti A, Piscaglia F, Caturelli E, Benvegnù L, Vivarelli M, Ercolani G, Cescon M, Ravaioli M, Grazi GL, Bolondi L, Pinna AD. Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol 2009; 16: 413-422 [PMID: 19034578 DOI: 10.1245/s10434-008-0232-4]
33. Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, Capussotti L, Calise F, Pellicci R, Belli G, Tagger A, Colombo M, Bonino F, Majno P, Llovet JM. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology 2006; 44: 1543-1554 [PMID: 17133492 DOI: 10.1002/hep.21415]
34. Xia Y, Qiu Y, Li J, Shi L, Wang K, Xi T, Shen F, Yan Z, Wu M. Adjuvant therapy with capecitabine postpones recurrence of hepatocellular carcinoma after curative resection: a randomized controlled trial. Ann Surg Oncol 2010; 17: 3137-3144 [PMID: 20602260 DOI: 10.1245/s10434-010-1148-3]
35. Nault JC, De Reyniès A, Villanueva A, Calderaro J, Rebouis-sou S, Couchy G, Decaens T, Franco D, Imbeaud S, Rousseau F, Azoulay D, Saric J, Blanc JF, Balabaud C, Bioulac-Sage P, Laurent A, Laurent-Puig P, Llovet JM, Zucman-Rossi J. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology 2013; 145: 176-187 [PMID: 23567350 DOI: 10.1053/j.gastro.2013.03.051]
36. Nishikawa H, Kimura T, Kita R, Osaki Y. Radiofrequency ablation for hepatocellular carcinoma. Int J Hyperthermia 2013; 29: 558-568 [PMID: 23937321 DOI: 10.3109/02656736.20 13.821528]
37. 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: 82-89 [PMID: 18008357 DOI: 10.1002/hep.21933]
38. 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: 514-524 [PMID: 19174803 DOI: 10.1038/ ajg.2008.80]
39. Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 2009; 49: 453-459 [PMID: 19065676 DOI: 10.1002/hep.22648]
40. Shen A, Zhang H, Tang C, Chen Y, Wang Y, Zhang C, Wu Z. Systematic review of radiofrequency ablation versus percutaneous ethanol injection for small hepatocellular carcinoma up to 3 cm. J Gastroenterol Hepatol 2013; 28: 793-800 [PMID: 23432154 DOI: 10.1111/jgh.12162]
41. Huang J, Yan L, Cheng Z, Wu H, Du L, Wang J, Xu Y, Zeng Y. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 2010; 252: 903-912 [PMID: 21107100 DOI: 10.1097/ SLA.0b013e3181efc656]
42. 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: 794-802 [PMID: 22634125 DOI: 10.1016/j.jhep.2012.05.007]
43. Hasegawa K, Kokudo N, Makuuchi M, Izumi N, Ichida T, Kudo M, Ku Y, Sakamoto M, Nakashima O, Matsui O, Matsuyama Y. Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey. J Hepatol 2013; 58: 724-729 [PMID: 23178708 DOI: 10.1016/j.jhep.2012.11.009]
44. Tohme S, Geller DA, Cardinal JS, Chen HW, Packiam V, Reddy S, Steel J, Marsh JW, Tsung A. Radiofrequency ablation compared to resection in early-stage hepatocellular carcinoma. HPB (Oxford) 2013; 15: 210-217 [PMID: 23374361 DOI: 10.1111/j.1477-2574.2012.00541.x]
45. Hasegawa K, Makuuchi M, Takayama T, Kokudo N, Arii S, Okazaki M, Okita K, Omata M, Kudo M, Kojiro M, Nakanuma Y, Takayasu K, Monden M, Matsuyama Y, Ikai I. Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a preliminary report of the Japanese nationwide survey. J Hepatol 2008; 49: 589-594 [PMID: 18620773]
46. 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 2006; 243: 321-328 [PMID: 16495695 DOI: 10.1097/01.sla.0000201480.65519.b8]
47. Lü MD, Kuang M, Liang LJ, Xie XY, Peng BG, Liu GJ, Li DM, Lai JM, Li SQ. [Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial]. Zhonghua Yixue Zazhi 2006; 86: 801-805 [PMID: 16681964]
48. Chen MS, Li JQ, Liang HH, Lin XJ, Guo RP, Zheng Y, Zhang YQ. [Comparison of effects of percutaneous radiofrequency ablation and surgical resection on small hepatocellular carcinoma]. Zhonghua Yixue Zazhi 2005; 85: 80-83 [PMID: 15774210]
49. Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediatesized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer 2010; 116: 5452-5460 [PMID: 20672352 DOI: 10.1002/ cncr.25314]
50. Cucchetti A, Piscaglia F, Cescon M, Colecchia A, Ercolani G, Bolondi L, Pinna AD. Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma. J Hepatol 2013; 59: 300-307 [PMID: 23603669 DOI: 10.1016/j.jhep.2013.04.009]
51. Forner A, Llovet JM, Bruix J. Chemoembolization for intermediate HCC: is there proof of survival benefit? J Hepatol 2012; 56: 984-986 [PMID: 22008737 DOI: 10.1016/j.jhep.2011.08.017]
52. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37: 429-442 [PMID: 12540794 DOI: 10.1053/jhep.2003.50047]
53. Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002; 359: 1734-1739 [PMID: 12049862 DOI: 10.1016/S0140-6736(02)08649-X]
54. 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: 1164-1171 [PMID: 11981766 DOI: 10.1053/jhep.2002.33156]
55. Golfieri R, Cappelli A, Cucchetti A, Piscaglia F, Carpenzano M, Peri E, Ravaioli M, D'Errico-Grigioni A, Pinna AD, Bolondi L. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (& lt; 5 cm) hepatocellular carcinomas. Hepatology 2011; 53: 1580-1589 [PMID: 21351114 DOI: 10.1002/hep.24246]
56. Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Cappelli A, Rodriguez M, Ettorre GM, Saltarelli A, Geatti O, Ahmadzadehfar H, Haug AR, Izzo F, Giampalma E, Sangro B, Pizzi G, Notarianni E, Vit A, Wilhelm K, Jakobs TF, Lastoria S. Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma. J Hepatol 2013; 59: 753-761 [PMID: 23707371 DOI: 10.1016/j.jhep.2013.05.025]
57. Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, Imamura H, Sugawara Y, Kokudo N, Makuuchi M. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008; 134: 1908-1916 [PMID: 18549877 DOI: 10.1053/ j.gastro.2008.02.091]
58. Torzilli G, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, Vauthey JN, Choti MA, De Santibanes E, Donadon M, Morenghi E, Makuuchi M. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg 2013; 257: 929-937 [PMID: 23426336 DOI: 10.1097/SLA.0b013e31828329b8]
59. Song MJ, Chun HJ, Song do S, Kim HY, Yoo SH, Park CH, Bae SH, Choi JY, Chang UI, Yang JM, Lee HG, Yoon SK. Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol 2012; 57: 1244-1250 [PMID: 22824821 DOI: 10.1016/j.jhep.2012.07.017]
60. Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, Benhamou Y, Avajon Y, Gruenberger T, Pomoni M, Langenberger H, Schuchmann M, Dumortier J, Mueller C, Chevallier P, Lencioni R. Prospective randomized study of doxorubicineluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010; 33: 41-52 [PMID: 19908093 DOI: 10.1007/ s00270-009-9711-7]
61. Nicolini D, Svegliati-Baroni G, Candelari R, Mincarelli C, Mandolesi A, Bearzi I, Mocchegiani F, Vecchi A, Montalti R, Benedetti A, Risaliti A, Vivarelli M. Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation. World J Gastroenterol 2013; 19: 5622-5632 [PMID: 24039354 DOI: 10.3748/wjg.v19.i34.5622]
62. Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M. The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol 2014; 60: 118-126 [PMID: 24012941 DOI: 10.1016/j.jhep.2013.08.022]
63. Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Trauner M, Peck-Radosavljevic M. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 2013; 57: 2261-2273 [PMID: 23316013 DOI: 10.1002/ hep.26256]
64. Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, Ettorre GM, Salvatori R, Giampalma E, Geatti O, Wilhelm K, Hoffmann RT, Izzo F, Iñarrairaegui M, Maini CL, Urigo C, Cappelli A, Vit A, Ahmadzadehfar H, Jakobs TF, Lastoria S. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011; 54: 868-878 [PMID: 21618574 DOI: 10.1002/hep.24451]
65. Lau WY, Sangro B, Chen PJ, Cheng SQ, Chow P, Lee RC, Leung T, Han KH, Poon RT. Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90. Oncology 2013; 84: 311-318 [PMID: 23615394 DOI: 10.1159/000348325]
66. Shah RP, Brown KT, Sofocleous CT. Arterially directed therapies for hepatocellular carcinoma. AJR Am J Roentgenol 2011; 197: W590-W602 [PMID: 21940531 DOI: 10.2214/ AJR.11.7554]
67. Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchianò A, Bongini M, Lanocita R, Civelli E, Bombardieri E, Camerini T, Spreafico C. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013; 57: 1826-1837 [PMID: 22911442 DOI: 10.1002/hep.26014]
68. Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, Sato KT, Gupta R, Nikolaidis P, Miller FH, Yaghmai V, Ibrahim SM, Senthilnathan S, Baker T, Gates VL, Atassi B, Newman S, Memon K, Chen R, Vogelzang RL, Nemcek AA, Resnick SA, Chrisman HB, Carr J, Omary RA, Abecassis M, Benson AB, Mulcahy MF. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011; 140: 497-507. e2 [PMID: 21044630 DOI: 10.1053/j.gastro.2010.10.049]
69. Sangro B, Iñarrairaegui M, Bilbao JI. Radioembolization for hepatocellular carcinoma. J Hepatol 2012; 56: 464-473 [PMID: 21816126 DOI: 10.1016/j.jhep.2011.07.012]
70. Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH, Sato KT, Wang E, Gupta R, Benson AB, Newman SB, Omary RA, Abecassis M, Kulik L. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 2010; 138: 52-64 [PMID: 19766639 DOI: 10.1053/j.gastro.2009.09.006]
71. Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives. Hepatology 2013; 58: 2188-2197 [PMID: 23512791 DOI: 10.1002/hep.26382]
72. Kim YH, Kim do Y. Yttrium-90 radioembolization for hepatocellular carcinoma: what we know and what we need to know. Oncology 2013; 84 Suppl 1: 34-39 [PMID: 23428856 DOI: 10.1159/000345887]
73. Lesurtel M, Müllhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidencebased analysis. Am J Transplant 2006; 6: 2644-2650 [PMID: 16939518 DOI: 10.1111/j.1600-6143.2006.01509.x]
74. Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, LeBlanc AC, Donovan DJ, Thung SN, Solé M, Tovar V, Alsinet C, Ramos AH, Barretina J, Roayaie S, Schwartz M, Waxman S, Bruix J, Mazzaferro V, Ligon AH, Najfeld V, Friedman SL, Sellers WR, Meyerson M, Llovet JM. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 2008; 68: 6779-6788 [PMID: 18701503 DOI: 10.1158/0008-5472.CAN-08-0742]
75. Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K, Miyoshi E, Monden M, Matsuura N. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma. Br J Cancer 2001; 84: 1377-1383 [PMID: 11355950 DOI: 10.1054/bjoc.2000.1580]
76. Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, Factor VM, Thorgeirsson SS. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006; 130: 1117-1128 [PMID: 16618406 DOI: 10.1053/ j.gastro.2006.01.006]
77. Sahin F, Kannangai R, Adegbola O, Wang J, Su G, Torbenson M. mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res 2004; 10: 8421-8425 [PMID: 15623621 DOI: 10.1158/1078-0432.CCR-04-0941]
78. Takami T, Kaposi-Novak P, Uchida K, Gomez-Quiroz LE, Conner EA, Factor VM, Thorgeirsson SS. Loss of hepatocyte growth factor/c-Met signaling pathway accelerates early stages of N-nitrosodiethylamine induced hepatocarcinogenesis. Cancer Res 2007; 67: 9844-9851 [PMID: 17942915 DOI: 10.1158/0008-5472.CAN-07-1905]
79. Breuhahn K, Longerich T, Schirmacher P. Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene 2006; 25: 3787-3800 [PMID: 16799620 DOI: 10.1038/ sj.onc.1209556]
80. 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: 835-844 [PMID: 17016424 DOI: 10.1038/nrd2130]
81. 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 2004; 64: 7099-7109 [PMID: 15466206 DOI: 10.1158/0008-5472. CAN-04-1443]
82. 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, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390 [PMID: 18650514 DOI: 10.1056/NEJMoa0708857]
83. 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 2009; 10: 25-34 [PMID: 19095497 DOI: 10.1016/ S1470-2045(08)70285-7]
84. Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA 2010; 304: 2154-2160 [PMID: 21081728 DOI: 10.1001/jama.2010.1672]
85. Prete SD, Montella L, Caraglia M, Maiorino L, Cennamo G, Montesarchio V, Piai G, Febbraro A, Tarantino L, Capasso E, Palmieri G, Guarrasi R, Bianco M, Mamone R, Savastano C, Pisano A, Vincenzi B, Sabia A, D'Agostino A, Faiola V, Addeo R. Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So. LAR. study. Cancer Chemother Pharmacol 2010; 66: 837-844 [PMID: 20041325 DOI: 10.1007/s00280-009-1226-z]
86. Yau TCP, Chan P, Cheung FY, Lee AS, Yau TK, Choo SP, Lau J, Wong JS, Fan ST, Poon RT. Phase II trial of sorafenib with capecitabine and oxaliplatin (SECOX) in patients with locally advanced or metastatic hepatocellular carcinoma. EJC 2009; Suppl 7: 20-21
87. Hsu CH, Shen YC, Lin ZZ, Chen PJ, Shao YY, Ding YH, Hsu C, Cheng AL. Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma. J Hepatol 2010; 53: 126-131 [PMID: 20416968 DOI: 10.1016/j.jhep.2010.01.035]
88. Giuliana FAR, Addeo R, Febbraio A, Rizzi D, Macello E, del Prete S, Pisconti S, Fico M, Colucci G. Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma: a phase II study by the Grupo Oncologico Dell'Italia Meridonale. (PROT. GOIM 2705). Cancer Treat Rev 2010; 36 Suppl 4: S96
89. Faivre SFL, Fartoux L, Bumsel F, Bouattor M, Dreyer C, Raymond E, Rosmorduc O. Phase I safety, pharmacokinetic, and pharmacodynamic study of AVE 1642, a human monoclonal antibody inhibiting the insulin-like grouth factor-1 receptor (IGF-1R/CD221), administered as single agent and in combination with sorafinib as first line therapy in patients with advanced hepatocellular carcinoma. Hepatology 2010; 52 Suppl: 466A, 288
90. Cheng A, Kang Y, Lin D, Park J, Kudo M, Qin S, Omata M, Lowenthal SW, Lanzalone S, Yang L, Lechuga M, Raymond E and SUN1170 HCC Study Group. Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC). J Clin Oncol 2011; 29 Suppl 15: 4000
91. Toh HC, Chen PJ, Carr BI, Knox JJ, Gill S, Ansell P, McKeegan EM, Dowell B, Pedersen M, Qin Q, Qian J, Scappaticci FA, Ricker JL, Carlson DM, Yong WP. Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma. Cancer 2013; 119: 380-387 [PMID: 22833179 DOI: 10.1002/cncr.27758]
92. Park JW, Finn RS, Kim JS, Karwal M, Li RK, Ismail F, Thomas M, Harris R, Baudelet C, Walters I, Raoul JL. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2011; 17: 1973-1983 [PMID: 21349999 DOI: 10.1158/1078-0432. CCR-10-2011]
93. Finn RS, Kang YK, Mulcahy M, Polite BN, Lim HY, Walters I, Baudelet C, Manekas D, Park JW. Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2012; 18: 2090-2098 [PMID: 22238246 DOI: 10.1158/1078-0432.CCR-11-1991]
94. Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn R, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW. Brivanib versus placebo in patients with advanced hepatocellular carcinoma (HCC) who failed or were intolerant to sorafenib: results from the phase 3 BRISK-PS study. EASL 2012; Abstract 1398
95. Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Aviña J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013; 31: 3517-3524 [PMID: 23980084 DOI: 10.1200/JCO.2012.48.4410]
96. Martell RE, Puzanov I, Ma WW, Santoro A, Dy GK, Goff LW, Fetterly GJ, Michael SA, Means-Powell JA, Chai F, Lamar M, Simonelli M, Chiang WM, Jarboe J, Schwartz BE, Adjei AA, Nashville TN, Buffalo NY, Woburn MA. Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with hepatocellular carcinoma (HCC) from a phase I study. Proc Am Soc Clin Oncol 2012; 30 Suppl: abstract 4117
97. Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013; 14: 55-63 [PMID: 23182627 DOI: 10.1016/ S1470-2045(12)70490-4]
98. Zhu AX, Abrams TA, Miksad R, Blaszkowsky LS, Meyerhardt JA, Zheng H, Muzikansky A, Clark JW, Kwak EL, Schrag D, Jors KR, Fuchs CS, Iafrate AJ, Borger DR, Ryan DP. Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. Cancer 2011; 117: 5094-5102 [PMID: 21538343 DOI: 10.1002/cncr.26165]
99. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067-4075 [PMID: 24081937 DOI: 10.1200/JCO.2012.45.8372]
100. Zhu AX, Rosmorduc O, Evans J, Ross P, Santoro A, Carriho FJ, Leberre M, Jensen M, Meinhardt G, Kang Y. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with hepatocellular carcinoma (HCC). Ann Oncol 2012; 23 Suppl: LBA2
101. Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK, PChen PJ, Toh HC, Gorbunova V, Eskens F, Qian J, McKee MD, Ricker JL, Carlson DM, Nowiemet SE. Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2012; 30 (Suppl 34): abstr 249
102. Gadani S, Mahvash A, Avritscher R, Chasen B, Kaseb A, Murthy R. Yttirum-90 resin microspheres as an adjunct to sorafenib in patients with unresectable HCC: A retrospective study for evaluation of survival benefit and adverse events. Society of Interventional Radiology Annual Scientific Meeting, 2013. Presented at: April 15, 2013: Abstract 62
103. Cabrera R, Pannu DS, Caridi J, Firpi RJ, Soldevila-Pico C, Morelli G, Clark V, Suman A, George TJ, Nelson DR. The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma. Aliment Pharmacol Ther 2011; 34: 205-213 [PMID: 21605146 DOI: 10.1111/ j.1365-2036.2011.04697.x]
104. Sansonno D, Lauletta G, Russi S, Conteduca V, Sansonno L, Dammacco F. Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial. Oncologist 2012; 17: 359-366 [PMID: 22334456 DOI: 10.1634/theoncologist.2011-0313]
105. Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J, Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G, Okita K. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer 2011; 47: 2117-2127 [PMID: 21664811 DOI: 10.1016/j.ejca.2011.05.007]
106. Chao Y, Lee HC, Lee TY, Yoon J, Han G, Yang J, Wang J, Kim B, Shao G, Chung YH. START (Study in Asia of the Combination of TACE (transcatheter arterial chemoembolization) with Sorafenib in Patients with Hepatocellular Carcinoma) Trial. 5th International Liver Cancer Association (ILCA) Annual Conference; 2011, September 1-3; Hong Kong: Wanchai, 2011: Abstract 0-Abstract 026
107. Han G, Yang J, Shao G, Teng G, Wang M, Yang J, Liu Z, Feng G, Yang R, Lu L, Chao Y, Wang J. Sorafenib in combination with transarterial chemoembolization in Chinese patients with hepatocellular carcinoma: a subgroup interim analysis of the START trial. Future Oncol 2013; 9: 403-410 [PMID: 23469975 DOI: 10.2217/fon.13.11]
108. Chung YH, Han G, Yoon JH, Yang J, Wang J, Shao GL, Kim BI, Lee TY, Chao Y. Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial. Int J Cancer 2013; 132: 2448-2458 [PMID: 23129123 DOI: 10.1002/ijc.27925]
109. Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N, Geschwind JF. Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 2011; 29: 3960-3967 [PMID: 21911714 DOI: 10.1200/JCO.2011.37.1021]
110. Meyer T, Fox R, Bird D, Watkinson A, Hacking N, Stocken D, Johnson PJ, Palmer DH. TACE 2: A randomized placebocontrolled, double-blinded, phase III trial evaluating sorafenib in combination with transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). J Clin Oncol 2012; 30 suppl: TPS4150