Liver cancer: Approaching a personalized care

Journal of Hepatology

Volumn 62, Issue S1, 2015, Pages S144-S156

  Bruix, Jordi ^a   Han, Kwang Hyub ^b   Gores, Gregory ^c   Llovet, Josep Maria ^a,d,e   Mazzaferro, Vincenzo ^f  

^a UNIVERSITY OF BARCELONA   (Spain)

^b Yonsei University College of Medicine   (South Korea)

^c MAYO CLINIC   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^e INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^f NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

HCC; iCCA; Liver cancer; Personalised treatment; Profiling

Indexed keywords

ANGIOGENESIS; BILE DUCT CARCINOMA; COMPUTER ASSISTED TOMOGRAPHY; DECOMPENSATED LIVER CIRRHOSIS; END STAGE LIVER DISEASE; HUMAN; LIVER CANCER; LIVER CELL CARCINOMA; LIVER TRANSPLANTATION; MALIGNANT TRANSFORMATION; MOLECULAR PATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PERSONALIZED MEDICINE; PRIORITY JOURNAL; REVIEW; SCREENING TEST; CHEMOEMBOLIZATION; CHOLANGIOCARCINOMA; GENETICS; LIVER NEOPLASMS; SIGNAL TRANSDUCTION;

CHEMOEMBOLIZATION, THERAPEUTIC; CHOLANGIOCARCINOMA; HUMANS; LIVER NEOPLASMS; LIVER TRANSPLANTATION; PRECISION MEDICINE; SIGNAL TRANSDUCTION;

EID: 84937517958     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2015.02.007     Document Type: Review

References (141)

1. B. Bressac, M. Kew, J. Wands, and M. Ozturk Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa Nature 350 1991 429 431 10.1038/350429a0
2. I.C. Hsu, R.A. Metcalf, T. Sun, J.A. Welsh, N.J. Wang, and C.C. Harris Mutational hotspot in the p53 gene in human hepatocellular carcinomas Nature 350 1991 427 428 10.1038/350427a0
3. V. Mazzaferro, E. Regalia, R. Doci, S. Andreola, A. Pulvirenti, F. Bozzetti, and et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis N Engl J Med 334 1996 693 699
4. J. Bruix, and M. Sherman Management of hepatocellular carcinoma: an update Hepatology 53 2011 1020 1022
5. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma J Hepatol 56 2012 908 943 10.1016/j.jhep.2011.12.001 pii: S0168-8278(11)00873-7
6. J.M. Llovet, and J. Bruix Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival Hepatology 37 2003 429 442
7. J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, J.F. Blanc, and et al. Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 2008 378 390 10.1056/NEJMoa0708857 pii: 359/4/378
8. A. Forner, J.M. Llovet, and J. Bruix Hepatocellular carcinoma Lancet 379 2012 1245 1255
9. M. Reig, A. Darnell, A. Forner, J. Rimola, C. Ayuso, and J. Bruix Systemic therapy for hepatocellular carcinoma: the issue of treatment stage migration and registration of progression using the BCLC-refined RECIST Semin Liver Dis 34 2014 444 455
10. N.J. Kassebaum, A. Bertozzi-Villa, M.S. Coggeshall, K.A. Shackelford, C. Steiner, K.R. Heuton, and et al. Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 Lancet 384 2014 980 1004 10.1016/S0140-6736(14)60696-6
11. http://globocan.iarc.fr/Pages/bar-sex-site-prev-sel.aspx. No Title n.d.
12. E.E. Calle, C. Rodriguez, K. Walker-Thurmond, and M.J. Thun Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults N Engl J Med 348 2003 1625 1638 10.1056/NEJMoa021423 pii: 348/17/1625
13. S.D. Saini, F. van Hees, and S. Vijan Smarter screening for cancer: possibilities and challenges of personalization JAMA 312 2014 2211 2212 10.1001/jama.2014.13933
14. M. Sherman, and M. Colombo Hepatocellular carcinoma screening and diagnosis Semin Liver Dis 34 2014 389 397 10.1055/s-0034-1394139
15. H.-I. Yang, M. Sherman, J. Su, P.-J. Chen, Y.-F. Liaw, U.H. Iloeje, and et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection J Clin Oncol 28 2010 2437 2444 10.1200/JCO.2009.27.4456
16. J.-C. Nault, and P. Nahon Genetic predisposition to hepatocellular carcinoma in alcoholic cirrhosis: the NCAN-PNPLA3-lipid connection? J Hepatol 61 2014 971 972 10.1016/j.jhep.2014.08.001
17. D.Y. Chiang, A. Villanueva, Y. Hoshida, J. Peix, P. Newell, B. Minguez, and et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma Cancer Res 68 2008 6779 6788 10.1158/0008-5472.CAN-08-0742
18. T. Yamashita, M. Forgues, W. Wang, J.W. Kim, Q. Ye, H. Jia, and et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma Cancer Res 68 2008 1451 1461 10.1158/0008-5472.CAN-07-6013
19. S. Boyault, D.S. Rickman, A. de Reynies, C. Balabaud, S. Rebouissou, E. Jeannot, and et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets Hepatology 45 2007 42 52 10.1002/hep.21467
20. K. Breuhahn, S. Vreden, R. Haddad, S. Beckebaum, D. Stippel, P. Flemming, and et al. Molecular profiling of human hepatocellular carcinoma defines mutually exclusive interferon regulation and insulin-like growth factor II overexpression Cancer Res 64 2004 6058 6064 10.1158/0008-5472.CAN-04-0292
21. Y. Hoshida, S. Toffanin, A. Lachenmayer, A. Villanueva, B. Minguez, and J.M. Llovet Molecular classification and novel targets in hepatocellular carcinoma: recent advancements Semin Liver Dis 30 2010 35 51 10.1055/s-0030-1247131
22. A. Villanueva, Y. Hoshida, C. Battiston, V. Tovar, D. Sia, C. Alsinet, and et al. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma Gastroenterology 140 2011 e2 10.1053/j.gastro.2011.02.006 pii: S0016-5085(11)00142-9
23. J.C. Nault, A. de Reynies, A. Villanueva, J. Calderaro, S. Rebouissou, G. Couchy, and et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection Gastroenterology 145 2013 176 187 10.1053/j.gastro.2013.03.051 pii: S0016-5085(13)00494-0
24. Y. Hoshida, A. Villanueva, M. Kobayashi, J. Peix, D.Y. Chiang, A. Camargo, and et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma N Engl J Med 359 2008 1995 2004 10.1056/NEJMoa0804525 pii: NEJMoa0804525
25. Y. Hoshida, A. Villanueva, A. Sangiovanni, M. Sole, C. Hur, K.L. Andersson, and et al. Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis Gastroenterology 144 2013 1024 1030 10.1053/j.gastro.2013.01.021 pii: S0016-5085(13)00078-4
26. C. Guichard, G. Amaddeo, S. Imbeaud, Y. Ladeiro, L. Pelletier, I.B. Maad, and et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma Nat Genet 44 2012 694 698 10.1038/ng.2256 pii: ng.2256
27. A. Villanueva, and J.M. Llovet Liver cancer in 2013: mutational landscape of HCC-the end of the beginning Nat Rev Clin Oncol 11 2014 73 74 10.1038/nrclinonc.2013.243
28. Y. Totoki, K. Tatsuno, K.R. Covington, H. Ueda, C.J. Creighton, M. Kato, and et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes Nat Genet 46 2014 1267 1273
29. E. Horwitz, I. Stein, M. Andreozzi, J. Nemeth, A. Shoham, O. Pappo, and et al. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to Sorafenib treatment Cancer Discov 4 2014 730 743 10.1158/2159-8290.CD-13-0782
30. D.F. Calvisi, S. Ladu, A. Gorden, M. Farina, E.A. Conner, J.S. Lee, and et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC Gastroenterology 130 2006 1117 1128 10.1053/j.gastro.2006.01.006
31. P. Newell, S. Toffanin, A. Villanueva, D.Y. Chiang, B. Minguez, L. Cabellos, and et al. Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo J Hepatol 51 2009 725 733 10.1016/j.jhep.2009.03.028
32. A. Villanueva, D.Y. Chiang, P. Newell, J. Peix, S. Thung, C. Alsinet, and et al. Pivotal role of mTOR signaling in hepatocellular carcinoma Gastroenterology 135 2008 10.1053/j.gastro.2008.08.008
33. M. Bhat, N. Sonenberg, and G.J. Gores The mTOR pathway in hepatic malignancies Hepatology 58 2013 810 818 10.1002/hep.26323
34. P. Kaposi-Novak, J.S. Lee, L. Gòmez-Quiroz, C. Coulouarn, V.M. Factor, and S.S. Thorgeirsson Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype J Clin Invest 116 2006 1582 1595 10.1172/JCI27236
35. V. Tovar, C. Alsinet, A. Villanueva, Y. Hoshida, D.Y. Chiang, M. Solé, and et al. IGF activation in a molecular subclass of hepatocellular carcinoma and pre-clinical efficacy of IGF-1R blockage J Hepatol 52 2010 550 559 10.1016/j.jhep.2010.01.015
36. J. Zucman-Rossi, S. Benhamouche, C. Godard, S. Boyault, G. Grimber, C. Balabaud, and et al. Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas Oncogene 26 2007 774 780 10.1038/sj.onc.1209824
37. A. Lachenmayer, C. Alsinet, R. Savic, L. Cabellos, S. Toffanin, Y. Hoshida, and et al. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib Clin Cancer Res 18 2012 4997 5007 10.1158/1078-0432.CCR-11-2322
38. C. Verslype, O. Rosmorduc, and P. Rougier Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol 23 2012 vii41 vii48 10.1093/annonc/mds225 pii: mds225
39. M. Sherman Alphafetoprotein: an obituary J Hepatol 34 2001 603 605
40. M. Sherman The resurrection of alphafetoprotein J Hepatol 52 2010 939 940 10.1016/j.jhep.2010.02.006 pii: S0168-8278(10)00107-8
41. T. Roskams, and M. Kojiro Pathology of early hepatocellular carcinoma: conventional and molecular diagnosis Semin Liver Dis 30 2010 17 25 10.1055/s-0030-1247129
42. J. Bruix, and M. Sherman Management of hepatocellular carcinoma Hepatology 42 2005 1020 1022
43. D.G. Mitchell, J. Bruix, M. Sherman, and C.B. Sirlin LI-RADS (Liver Imaging Reporting and Data System): Summary, discussion, consensus of the LI-RADS Management Working Group and future directions Hepatology 2014 10.1002/hep.27304
44. A. Forner, R. Vilana, C. Ayuso, L. Bianchi, M. Sole, J.R. Ayuso, and et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma Hepatology 47 2008 97 104 10.1002/hep.21966
45. C. Ma, S. Bandukwala, D. Burman, J. Bryson, D. Seccareccia, S. Banerjee, and et al. Interconversion of three measures of performance status: an empirical analysis Eur J Cancer 46 2010 3175 3183 10.1016/j.ejca.2010.06.126
46. R.N. Pugh, I.M. Murray-Lyon, J.L. Dawson, M.C. Pietroni, and R. Williams Transection of the oesophagus for bleeding oesophageal varices Br J Surg 60 1973 646 649
47. E.A. Tsochatzis, J. Bosch, and A.K. Burroughs Liver cirrhosis Lancet 383 2014 1749 1761 10.1016/S0140-6736(14)60121-5 pii: S0140-6736(14)60121-5
48. M. Malinchoc, P.S. Kamath, F.D. Gordon, C.J. Peine, J. Rank, and P.C. Ter Borg A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts Hepatology 31 2000 864 871 10.1053/he.2000.5852 pii: S0270913900980704
49. P. Martin, A. DiMartini, S. Feng, R. Brown Jr., and M. Fallon Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation Hepatology 59 2014 1144 1165
50. M. Mazaferro, R. Lencioni, and P. Majno Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation Semin Liver Dis 34 2014 415 426
51. M. Burrel, M. Reig, A. Forner, M. Barrufet, C.R. De Lope, S. Tremosini, and et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design J Hepatol 56 2012 1330 1335 10.1016/j.jhep.2012.01.008
52. K. Takayasu, S. Arii, I. Ikai, M. Kudo, Y. Matsuyama, M. Kojiro, and et al. Overall survival after transarterial lipiodol infusion chemotherapy with or without embolization for unresectable hepatocellular carcinoma: propensity score analysis AJR Am J Roentgenol 194 2010 830 837 10.2214/AJR.09.3308 pii: 194/3/830
53. K. Malagari, M. Pomoni, H. Moschouris, E. Bouma, J. Koskinas, A. Stefaniotou, and et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis Cardiovasc Intervent Radiol 35 2012 1119 1128 10.1007/s00270-012-0394-0
54. I. Bargellini, R. Sacco, E. Bozzi, M. Bertini, B. Ginanni, A. Romano, and et al. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study Eur J Radiol 81 2012 1173 1178 10.1016/j.ejrad.2011.03.046
55. A. Cucchetti, F. Piscaglia, M. Cescon, A. Colecchia, G. Ercolani, L. Bolondi, and et al. Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma J Hepatol 59 2013 300 307 10.1016/j.jhep.2013.04.009
56. S. Okada, K. Shimada, J. Yamamoto, T. Takayama, T. Kosuge, S. Yamasaki, and et al. Predictive factors for postoperative recurrence of hepatocellular carcinoma Gastroenterology 106 1994 1618 1624 pii: S0016508594001824
57. E. Adachi, T. Maeda, T. Matsumata, K. Shirabe, N. Kinukawa, K. Sugimachi, and et al. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma Gastroenterology 108 1995 768 775
58. F.Y. Yao, L. Ferrell, N.M. Bass, J.J. Watson, P. Bacchetti, A. Venook, and et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival Hepatology 33 2001 1394 1403
59. V. Mazzaferro, J.M. Llovet, R. Miceli, S. Bhoori, M. Schiavo, L. Mariani, and et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis Lancet Oncol 10 2009 35 43 10.1016/S1470-2045(08)70284-5 pii: S1470-2045(08)70284-5
60. C. Duvoux, F. Roudot-Thoraval, T. Decaens, F. Pessione, H. Badran, T. Piardi, and et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria Gastroenterology 143 2012 985 986 10.1053/j.gastro.2012.05.052 pii: S0016-5085(12)00941-9
61. C. Toso, G. Mentha, and P. Majno Selection of patients with hepatocellular carcinoma before liver transplantation: need to combine alpha-fetoprotein with morphology? Hepatobiliary Pancreat Dis Int 9 2010 460 461 pii: 1395
62. C. Toso, J. Trotter, A. Wei, D.L. Bigam, S. Shah, J. Lancaster, and et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma Liver Transpl 14 2008 1107 1115 10.1002/lt.21484
63. P.A. Clavien, M. Lesurtel, P.M. Bossuyt, G.J. Gores, B. Langer, and A. Perrier Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report Lancet Oncol 13 2012 e11 e22 10.1016/S1470-2045(11)70175-9 pii: S1470-2045(11)70175-9
64. J. Bruix, G.J. Gores, and V. Mazzaferro Hepatocellular carcinoma: clinical frontiers and perspectives Gut 63 2014 844 855 10.1136/gutjnl-2013-306627 pii: gutjnl-2013-306627
65. C. Toso, V. Mazzaferro, J. Bruix, R. Freeman, and G.M.P. Mentha Toward a better liver graft allocation that accounts for candidates with and without hepatocellular carcinoma Am J Transpl 4 2014 2221 2227
66. A. Berzigotti, M. Reig, J.G. Abraldes, and J.B.J. Bosch Portal hypertension on the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis Hepatology 61 2015 526 536
67. J. Bruix, A. Castells, J. Bosch, F. Feu, J. Fuster, J.C. Garcia-Pagan, and et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure Gastroenterology 111 1996 1018 1022
68. T. Livraghi, F. Meloni, M. Di Stasi, E. Rolle, L. Solbiati, C. Tinelli, and et al. 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 2008 82 89 10.1002/hep.21933
69. H. Imamura, Y. Matsuyama, E. Tanaka, T. Ohkubo, K. Hasegawa, S. Miyagawa, and et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy J Hepatol 38 2003 200 207
70. M. Sala, J. Fuster, J.M. Llovet, M. Navasa, M. Sole, M. Varela, and et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation Liver Transpl 10 2004 1294 1300
71. D. Fuks, S. Dokmak, V. Paradis, M. Diouf, F. Durand, and J. Belghiti Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis Hepatology 55 2012 132 140 10.1002/hep.24680
72. P.E. Majno, G. Mentha, and V. Mazzaferro Partial hepatectomy versus radiofrequency ablation for hepatocellular carcinoma: confirming the trial that will never be, and some comments on the indications for liver resection Hepatology 51 2010 1116 1118 10.1002/hep.23648
73. Y.C. Hsu, H.J. Ho, M.S. Wu, J.T. Lin, and C.Y. Wu Postoperative peg-interferon plus ribavirin is associated with reduced recurrence of hepatitis C virus-related hepatocellular carcinoma Hepatology 58 2013 150 157 10.1002/hep.26300
74. L.C. Lu, and A.L.P.R. Cheng Recent advances in the prevention of hepatocellular carcinoma recurrence Semin Liver Dis 34 2014 427 434
75. Y.K. Cho, J.K. Kim, M.Y. Kim, H. Rhim, and J.K. Han Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies Hepatology 49 2009 453 459 10.1002/hep.22648
76. J.L. Raoul, J. Bruix, T.F. Greten, M. Sherman, V. Mazzaferro, P. Hilgard, and et al. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses J Hepatol 56 2012 1080 1088 10.1016/j.jhep.2011.12.009 pii: S0168-8278(12)00047-5
77. J.P. May, and S.-D. Li Hyperthermia-induced drug targeting Expert Opin Drug Deliv 10 2013 511 527 10.1517/17425247.2013.758631
78. Tak W, Lin S, Wang Y, Zheng J, Izzo F PS et al. Phase 3, randomized, double-blind, dummy-controlled, trial of radiofrequency ablation (RFA) + lyso-thermosensitive liposomal doxorubicin (LTLD, Thermodox), for hepatocellular carcinoma (HCC) lesions 3-7 cm. In: 7th Annu Conf Int Liver Cancer Assoc 2013:16.
79. Z.W. Peng, Y.Q.J. Zhang, M.S. Chen, L. Xu, H.H. Liang, X.J. Lin, and et al. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial J Clin Oncol 31 2013 426 432 10.1200/JCO.2012.42.9936 pii: JCO.2012.42.9936
80. R. Lencioni, L. Crocetti, P. Petruzzi, and et al. Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study J Hepatol 49 2008 217 222 10.1016/j.jhep.2008.03.021
81. S. Yan, D. Xu, and B. Sun Combination of radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis Dig Dis Sci 58 2013 2107 2113 10.1007/s10620-013-2570-8
82. S.M. Tadavarthy, L. Knight, T.W. Ovitt, and C.A.K. Snyder Therapeutic transcatheter arterial embolization Radiology 112 1974 13 16
83. J.M. Llovet, M.I. Real, X. Montana, R. Planas, S. Coll, J. Aponte, and et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial Lancet 359 2002 1734 1739
84. C.M. Lo, H. Ngan, W.K. Tso, C.L. Liu, C.M. Lam, R.T.P. Poon, and et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma Hepatology 35 2002 1164 1171 10.1053/jhep.2002.33156 pii: S0270913902877138
85. D.Y. Kim, and K.-H. Han How to improve treatment outcomes for hepatocellular carcinoma of intermediate and advanced stage Dig Dis 30 2012 598 602 10.1159/000343088
86. J.L. Raoul, B. Sangro, A. Forner, V. Mazzaferro, F. Piscaglia, L. Bolondi, and et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization Cancer Treat Rev 37 2010 212 220 10.1016/j.ctrv.2010.07.006 pii: S0305-7372(10)00131-3
87. M. Varela, M.I. Real, M. Burrel, A. Forner, M. Sala, M. Brunet, and et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics J Hepatol 46 2007 474 481
88. A.L. Lewis, M.V. Gonzalez, A.W. Lloyd, B. Hall, Y. Tang, S.L. Willis, and et al. DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization J Vasc Interv Radiol 17 2006 335 342 10.1097/01.RVI.0000195323.46152.B3
89. J. Lammer, K. Malagari, T. Vogl, F. Pilleul, A. Denys, A. Watkinson, and et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study Cardiovasc Intervent Radiol 33 2009 41 52 10.1007/s00270-009-9711-7
90. A. Sergio, C. Cristofori, R. Cardin, G. Pivetta, R. Ragazzi, A. Baldan, and et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness Am J Gastroenterol 103 2008 914 921 10.1111/j.1572-0241.2007.01712.x
91. R. Lencioni, J.M. Llovet, G. Han, W.-Y. Tak, J. Yang, M.-A. Leberre, and et al. Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): Phase II, randomized, double-blind SPACE trial J Clin Oncol 30 2012 abstr LBA154
92. M. Kudo, K. Imanaka, N. Chida, K. Nakachi, W.Y. Tak, T. Takayama, and et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma Eur J Cancer 47 2011 2117 2127 10.1016/j.ejca.2011.05.007 pii: S0959-8049(11)00324-8
93. B. Sangro, M. Inarrairaegui, and J.I. Bilbao Radioembolization for hepatocellular carcinoma J Hepatol 56 2012 464 473 10.1016/j.jhep.2011.07.012 pii: S0168-8278(11)00574-5
94. R. Salem, V. Mazzaferro, and B. Sangro Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: Biological lessons, current challenges, and clinical perspectives Hepatology 58 2013 2188 2197 10.1002/hep.26382
95. K. Memon, L. Kulik, R.J. Lewandowski, E. Wang, A. Riaz, R.K. Ryu, and et al. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times Gastroenterology 141 2011 526 535 10.1053/j.gastro.2011.04.054 535 e1-e2, pii: S0016-5085(11)00609-3
96. R. Salem, R.J. Lewandowski, M.F. Mulcahy, A. Riaz, R.K. Ryu, S. Ibrahim, and et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes Gastroenterology 138 2010 52 64 10.1053/j.gastro.2009.09.006 pii: S0016-5085(09)01574-1
97. B. Sangro, L. Carpanese, R. Cianni, R. Golfieri, D. Gasparini, S. Ezziddin, and et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation Hepatology 54 2011 868 878 10.1002/hep.24451
98. K.H. Han, M. Kudo, S.L. Ye, J.Y. Choi, R.T.P. Poon, J. Seong, and et al. Asian consensus workshop report: Expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia Oncology 81 2011 158 164 10.1159/000333280
99. M. Kudo Treatment of advanced hepatocellular carcinoma with emphasis on hepatic arterial infusion chemotherapy and molecular targeted therapy Liver Cancer 1 2012 62 70 10.1159/000342402
100. I.J. Lee, and J. Seong Radiotherapeutic strategies in the management of hepatocellular carcinoma Oncology 81 2011 123 133 10.1159/000333275
101. H. Blomgren, I. Lax, I. Näslund, R. Svanström, and R. Svanstrom Stereotactic high dose fraction radiation therapy of clinical experience of the first thirty-one patients Acta Oncol 34 1995 861 870
102. D.L. Andolino, C.S. Johnson, M. Maluccio, P. Kwo, A.J. Tector, J. Zook, and et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma Int J Radiat Oncol Biol Phys 81 2011 10.1016/j.ijrobp.2011.04.011
103. R.V. Tse, M. Hawkins, G. Lockwood, J.J. Kim, B. Cummings, J. Knox, and et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma J Clin Oncol 26 2008 657 664 10.1200/JCO.2007.14.3529; 10.1200/JCO.2007.14.3529
104. S. Qin, Y. Bai, H.Y. Lim, S. Thongprasert, Y. Chao, J. Fan, and et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia J Clin Oncol 31 2013 3501 3508 10.1200/JCO.2012.44.5643 pii: JCO.2012.44.5643
105. A.L. Cheng, Y.K. Kang, Z. Chen, C.J. Tsao, S. Qin, J.S. Kim, and 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 10 2009 25 34 10.1016/S1470-2045(08)70285-7 pii: S1470-2045(08)70285-7
106. A.L. Cheng, Y.K. Kang, D.Y. Lin, J.W. Park, M. Kudo, S. Qin, and et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial J Clin Oncol 31 2013 4067 4075 10.1200/JCO.2012.45.8372 pii: JCO.2012.45.8372
107. P.J. Johnson, S. Qin, J.W. Park, R.T. Poon, J.L. Raoul, P.A. Philip, and et 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 31 2013 3517 3524 10.1200/JCO.2012.48.4410 pii: JCO.2012.48.4410
108. C. Cainap, S. Qin, W.-T. Huang, I.-J. Chung, H. Pan, Y. Cheng, and et al. Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) J Clin Oncol 31 2013 abstr 249
109. A.X. Zhu, O. Rosmorduc, and J. Evans SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with hepatocellular carcinoma (HCC) Ann Oncol 23 2012 Abstract LBA2
110. J.M. Llovet, T. Decaens, J.L. Raoul, E. Boucher, M. Kudo, C. Chang, and et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study J Clin Oncol 31 2013 3509 3516 10.1200/JCO.2012.47.3009 pii: JCO.2012.47.3009
111. A.X. Zhu, M. Kudo, E. Assenat, S. Cattan, Y.K. Kang, H.Y. Lim, and et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial JAMA 312 2014 57 67 10.1001/jama.2014.7189 pii: 1884577
112. A.X. Zhu, B. Ryoo, C. Yen, M. Kudo, R.T. Poon, D. Pastorelli, and et al. Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC) following first-line therapy with sorafenib: results from the randomized phase III REACH study Ann Oncol 25 2014 ESMO 2014. LBA16
113. M. Reig, J. Rimola, F. Torres, A. Darnell, C. Rodriguez-Lope, A. Forner, and et al. Post-progression survival of patients with advanced hepatocellular carcinoma. Rationale for second line trial design Hepatology 2013 2023 2031 10.1002/hep.26586
114. M. Reig, F. Torres, C. Rodriguez-Lope, A. Forner, N. LLarch, J. Rimola, and et al. Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib J Hepatol 61 2014 318 324 10.1016/j.jhep.2014.03.030 pii: S0168-8278(14)00211-6
115. E. Crowley, F. Di Nicolantonio, F. Loupakis, and A. Bardelli Liquid biopsy: monitoring cancer-genetics in the blood Nat Rev Clin Oncol 10 2013 472 484 10.1038/nrclinonc.2013.110 pii: nrclinonc.2013.110
116. A. Santoro, L. Rimassa, I. Borbath, B. Daniele, S. Salvagni, J.L. Van Laethem, and et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study Lancet Oncol 14 2013 55 63 10.1016/S1470-2045(12)70490-4
117. W. Yeo, H.C. Chung, S.L. Chan, L.Z. Wang, R. Lim, J. Picus, and et al. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Res J Clin Oncol 30 2012 3361 3367 10.1200/JCO.2011.41.2395 pii: JCO.2011.41.2395
118. J. Akiba, O. Nakashima, S. Hattori, K. Tanikawa, M. Takenaka, M. Nakayama, and et al. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification Am J Surg Pathol 37 2013 496 505 10.1097/PAS.0b013e31827332b0
119. O. Govaere, M. Komuta, J. Berkers, B. Spee, C. Janssen, F. de Luca, and et al. Keratin 19: a key role player in the invasion of human hepatocellular carcinomas Gut 63 2013 674 685 10.1136/gutjnl-2012-304351 pii: gutjnl-2012-304351
120. B. Fan, Y. Malato, D.F. Calvisi, S. Naqvi, N. Razumilava, S. Ribback, and et al. Cholangiocarcinomas can originate from hepatocytes in mice J Clin Invest 122 2012 2911 2915 10.1172/JCI63212
121. J. Bridgewater, P.R. Galle, S.A. Khan, J.M. Llovet, J.W. Park, T. Patel, and et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma J Hepatol 60 2014 1268 1289
122. T. Patel Worldwide trends in mortality from biliary tract malignancies BMC Cancer 2 2002 10 10.1186/1471-2407-2-10
123. W.C. Palmer, and T. Patel Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma J Hepatol 57 2012 69 76 10.1016/j.jhep.2012.02.022
124. C.K. Ong, C. Subimerb, C. Pairojkul, S. Wongkham, I. Cutcutache, W. Yu, and et al. Exome sequencing of liver fluke-associated cholangiocarcinoma Nat Genet 44 2012 690 693 10.1038/ng.2273
125. Y. Jiao, T.M. Pawlik, R.A. Anders, F.M. Selaru, M.M. Streppel, D.J. Lucas, and et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas Nat Genet 45 2013 1470 1473 10.1038/ng.2813
126. J.B. Andersen, B. Spee, B.R. Blechacz, I. Avital, M. Komuta, A. Barbour, and et al. Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors Gastroenterology 142 2012 10.1053/j.gastro.2011.12.005
127. T.L. Gu, X. Deng, F. Huang, M. Tucker, K. Crosby, V. Rimkunas, and et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma PLoS One 6 2011 10.1371/journal.pone.0015640
128. B.R. Kipp, J.S. Voss, S.E. Kerr, E.G. Barr Fritcher, R.P. Graham, L. Zhang, and et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma Hum Pathol 43 2012 1552 1558 10.1016/j.humpath.2011.12.007
129. S.K. Saha, C.A. Parachoniak, K.S. Ghanta, J. Fitamant, K.N. Ross, M.S. Najem, and et al. Mutant IDH inhibits HNF-4á to block hepatocyte differentiation and promote biliary cancer Nature 2014 10.1038/nature13441
130. S. Rizvi, and G.J. Gores Pathogenesis, diagnosis, and management of cholangiocarcinoma Gastroenterology 145 2013 1215 1229 10.1053/j.gastro.2013.10.013
131. Y.M. Wu, F. Su, S. Kalyana-Sundaram, N. Khazanov, B. Ateeq, X. Cao, and et al. Identification of targetable FGFR gene fusions in diverse cancers Cancer Discov 3 2013 636 647 10.1158/2159-8290.CD-13-0050
132. Y. Arai, Y. Totoki, F. Hosoda, T. Shirota, N. Hama, H. Nakamura, and et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma Hepatology 59 2014 1427 1434 10.1002/hep.26890
133. M.J. Borad, M.D. Champion, J.B. Egan, W.S. Liang, R. Fonseca, A.H. Bryce, and et al. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma PLoS Genet 10 2014 10.1371/journal.pgen.1004135
134. N. Razumilava, and G.J. Gores Cholangiocarcinoma Lancet 2014 10.1016/S0140-6736(13)61903-0 pii: S0140-6736(13)61903-0
135. F.C. Gleeson, E. Rajan, M.J. Levy, J.E. Clain, M.D. Topazian, G.C. Harewood, and et al. EUS-guided FNA of regional lymph nodes in patients with unresectable hilar cholangiocarcinoma Gastrointest Endosc 67 2008 438 443 10.1016/j.gie.2007.07.018
136. J. Valle, H. Wasan, D.H. Palmer, D. Cunningham, A. Anthoney, A. Maraveyas, and et al. Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer N Engl J Med 362 2010 1273 1281 10.1056/NEJMoa0908721
137. G. Sapisochin, C. Rodríguez De Lope, M. Gastaca, J. Ortiz De Urbina, M.A. Suarez, J. Santoyo, and et al. "very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant 14 2014 660 667 10.1111/ajt.12591
138. K. Maganty, D. Levi, J. Moon, P.A. Bejarano, L. Arosemena, A. Tzakis, and et al. Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma: outcome after liver transplantation Dig Dis Sci 55 2010 3597 3601 10.1007/s10620-010-1402-3
139. G. Sapisochin, N. Fidelman, J.P. Roberts, and F.Y. Yao Mixed hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma in patients undergoing transplantation for hepatocellular carcinoma Liver Transpl 17 2011 934 942 10.1002/lt.22307
140. M. Garancini, P. Goffredo, F. Pagni, F. Romano, S. Roman, J.A. Sosa, and et al. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor Liver Transpl 20 2014 952 959 10.1002/lt.23897
141. G. Sapisochin, C.R. de Lope, M. Gastaca, J.O. de Urbina, R. López-Andujar, F. Palacios, and et al. Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study Ann Surg 259 2014 944 952 10.1097/SLA.0000000000000494