Zusammenfassung
Das hepatozelluläre Karzinom (HCC) ist weltweit eine der führenden krebsbedingten Todesursachen. Die Mehrzahl aller HCC entsteht auf dem Boden einer Leberzirrhose. Dies verkompliziert die Diagnostik und Therapie. Zur nicht invasiven Diagnostik sind klare Kriterien entwickelt worden, die auf kontrastverstärkten dynamischen bildgebenden Verfahren und dem Serum-Tumormarkerspiegel des AFP (Alpha-Fetoprotein) beruhen. Bei der Planung der Therapie müssen neben der Tumorausdehnung und -ausbreitung auch der Allgemeinzustand des Patienten und insbesondere die Leberfunktion mitberücksichtigt werden. Zur Einschätzung der Prognose und Planung der geeigneten Therapie hat sich hier insbesondere das BCLC-System der Barcelona Clinic for Liver Cancer bewährt. Nur etwa ein Drittel aller Patienten kann mittels Resektion, Transplantation oder lokaler Tumorablation kurativ behandelt werden. In den lokal fortgeschrittenen Fällen kommen v. a. transarterielle Verfahren wie die transarterielle Chemoembolisation und neuerdings die selektive interne Radiotherapie zum Einsatz. Da das HCC ein relativ chemotherapieresistenter Tumor ist, spielt die Chemotherapie kaum eine Rolle in der Therapie des HCC. Mit der Einführung des Sorafenib steht jetzt erstmals eine wirkungsvolle systemische Therapie für das fortgeschrittene und metastasierte HCC zur Verfügung. Einen besonderen Stellenwert hat die interdisziplinäre Betreuung von Patienten mit HCC, um alle für den einzelnen Patienten relevanten Therapieoptionen ausnutzen zu können.
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. The majority of HCCs develops on the basis of a chronic liver disease. This often complicates diagnosis and therapy. Non-invasive diagnostic criteria are based on dynamic imaging techniques and the serum level of AFP (alpha-fetoprotein). When evaluating HCC patients for therapy, besides tumor burden and localisation, the therapeutic evaluation must also consider the general condition of the patient and his/her liver function. For this purpose, the BCLC algorithm of the Barcelona Clinic for Liver Disease has proven helpful. Only one-third of the patients can be cured by resection, transplantation or local tumour ablation. In locally advanced cases transarterial procedures including transarterial chemoembolisation and radioembolisation are applied. HCC is a chemo-resistant tumour and chemotherapy is not accepted as standard of care in HCC. Sorafenib is the first systemic treatment with proven efficacy approved for the treatment of advanced and metastatic HCC. Interdisciplinary management of HCC patients is essential in order to provide every patient with the optimal therapy at his specific stage of disease.
Schlüsselwörter
hepatozelluläres Karzinom - Lebertransplantation - transarterielle Chemoembolisation - Radiofrequenzablation - Sorafenib
Key words
hepatocellular carcinoma - liver transplantation - transarterial chemoembolisation - radiofrequency ablation - sorafenib
Literatur
1
Parkin D M, Bray F, Ferlay J. et al .
Estimating the world cancer burden: Globocan 2000.
Int J Cancer.
2001;
94
153-156
2
Altekruse S, McGlynn K A, Reichman M E.
Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005.
J Clin Oncol.
2009;
27
1485-1491
3 London W T, McGlynn K A. Liver cancer. Schottenfeld D, Fraumeni JF Jr Cancer Epidemiology and Prevention New York; Oxford University Press 2006 3. Aufl: 763-786
4
Sun C A, Wu D M, Lin C C. et al .
Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan.
Am J Epidemiol.
2003;
157
674-682
5
Sakuma K, Saitoh N, Kasai M. et al .
Relative risks of death due to liver disease among Japanese male adults having various statuses for hepatitis B s and e antigen/antibody in serum: a prospective study.
Hepatology.
1988;
8
1642-1646
6
El-Serag H B, Tran T, Everhart J E.
Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.
Gastroenterology.
2004;
126
460-468
7
Calle E E, Rodriguez C, Walker-Thurmond K. et al .
Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U. S. adults.
N Engl J Med.
2003;
348
1625-1638
8
Maylin S, Martinot-Peignoux M, Moucari R. et al .
Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C.
Gastroenterology.
2008;
135
821-829
9
George S L, Bacon B R, Brunt E M. et al .
Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients.
Hepatology.
2009;
49
729-738
10
D’Amico G, Garcia-Tsao G, Pagliaro L.
Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies.
J Hepatol.
2006;
44
217-231
11
Bruix J, Sherman M.
AASLD Guideline: Management of hepatocellular carcinoma.
Hepatology.
2005;
42
1208-1236
12
Matsui O.
Imaging of multistep human hepatocarcinogenesis by CT during intraarterial contrast injection.
Intervirology.
2004;
47
271-276
13
Kelekis N L, Semelka R C, Worawattanakul S. et al .
Hepatocellular carcinoma in North America: a multiinstitutional study of appearance on T 1-weighted, T 2-weighted, and serial gadolinium-enhanced gradient-echo images.
Am J Roentgenol.
1998;
170
1005-1013
14
Hwang G J, Kim M J, Yoo H S. et al .
Nodular hepatocellular carcinomas: detection with arterial-, portal-, and delayed-phase images at spiral CT.
Radiology.
1997;
202
383-388
15
Willatt J M, Hussain H K, Adusumilli S. et al .
MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies.
Radiology.
2008;
247
311-330
16
Schacherer D, Girlich C, Jung M E. et al .
Transabdominal ultrasound with echoenhancement by contrast media in the diagnosis of hepatocellular carcinoma.
Dig Dis.
2009;
27
109-113
17
Kim S J, Kim S H, Lee J. et al .
Ferucarbotranenhanced 3.0-T magnetic resonance imaging using parallel imaging technique compared with triple-phase multidetector row computed tomography for the preoperative detection of hepatocellular carcinoma.
J Comput Assist Tomogr.
2008;
32
379-385
18
Kim Y K, Kwak H S, Han Y M. et al .
Usefulness of combining sequentially acquired gadobenate dimeglumine-enhanced magnetic resonance imaging and resovist-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: comparison with computed tomography hepatic arteriography and computed tomography arterioportography using 16-slice multidetector computed tomography.
J Comput Assist Tomogr.
2007;
31
702-711
19
Kim S H, Kim S H, Lee J. et al .
Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma.
Am J Roentgenol.
2009;
192
1675-1681
20
Zech C J, Reiser M F, Herrmann K A.
Imaging of hepatocellular carcinoma by computed tomography and magnetic resonance imaging: state of the art.
Dig Dis.
2009;
27
114-124
21
Burrel M, Llovet J M, Ayuso C. et al .
Barcelona Clínic Liver Cancer Group. MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation.
Hepatology.
2003;
38
1034-1042
22
Stoker J, Romijn M G, Man R A. et al .
Prospective comparative study of spiral computer tomography and magnetic resonance imaging for detection of hepatocellular carcinoma.
Gut.
2002;
51
105-107
23
Marin de D, Di Martino M, Guerrisi A. et al .
Hepatocellular carcinoma in patients with cirrhosis: qualitative comparison of gadobenate dimeglumine-enhanced MR imaging and multiphasic 64-section CT.
Radiology.
2009;
251
85-95
24
Kim K Y, Kim C S, Chung G H. et al .
Comparison of Gadobenate Dimeglumine-Enhanced dynamic MRI and 16-MDCT for the detection of hepatocellular carcinoma.
Am J Roentgenol.
2006;
186
149-157
25
Choi S H, Lee J M, Yu N C. et al .
Hepatocellular carinoma in liver transplantation candidates: detection with Gadobenate Dimeglumine-enhanced MRI.
Am J Roentgenol.
2008;
191
529-536
26
Kim S H, Choi B I, Lee J Y. et al .
Diagnostic Accuracy of Multi-/single-Detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation.
Intervirology.
2008;
51
52-60
27
Wang J H, Lu S N, Hung C H. et al .
Small hepatic nodules (≦ 2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.
Liver international.
2006;
26
928-934
28
Dai Y, Chen M H, Fan Z H. et al .
Diagnosis of small hepatic nodules detected by surveillance ultrasound in patients with cirrhosis: Comparison between contrast-enhanced ultrasound and contrast-enhanced helical computed tomography.
Hepatology Res.
2008;
38
281-290
29
Park J W, Kim J H, Kim S K. et al .
A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma.
J Nucl Med.
2008;
49
1912-1921
30 Lamerz R, Hayes P, Hoffmann R T. et al .NACB: Practice guidelines and recommendations for use of tumour markers in the clinic-Liver Cancer Manuscript (3D). 2005 http://www.nacb.org/lmpg/tumour_lmpg_draft.stm
31
Chen D, Sung J, Shen J. et al .
Serum alpha-fetoprotein in early stages of human hepatocellular carcinoma.
Gastroenterology.
1984;
86
1404-1409
32
Soreide O, Czerniak A, Bradpiece H. et al .
Characteristics of fibrolamellar hepatocellular carcinoma. A study of nine cases and review of the literature.
Am J Surg.
1986;
151
518-523
33
Fasani P, Sangiovanni A, De Fazio C. et al .
High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis attributable to multiple risk factors.
Hepatology.
1999;
29
1704-1707
34
Mita Y, Aoyagi Y, Yanagi M. et al .
The usefulness of determining des-gamma-carboxy prothrombin by sensitive enzyme immunoassay in the early diagnosis of patients with hepatocellular carcinoma.
Cancer.
1998;
82
1643-1648
35
Okuda H, Nakanishi T, Takatsu K. et al .
Measurement of serum levels of des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma by a revised enzyme immunoassay kit with increased sensitivity.
Cancer.
1999;
85
812-818
36
Tanaka Y, Kashiwagi T, Tsutsumi H. et al .
Sensitive measurement of serum abnormal prothrombin (PIVKA-II) as a marker of hepatocellular carcinoma.
Hepatogastroenterology.
1999;
46
2464-2468
37
Okuda H, Nakanishi T, Takatsu K. et al .
Serum levels of des-gamma-carboxy prothrombin measured using the revised enzyme immunoassay kit with increased sensitivity in relation to clinicopathologic features of solitary hepatocellular carcinoma.
Cancer.
2000;
88
544-549
38
Marrero J A, Su G L, Wei W. et al .
Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients.
Hepatology.
2003;
37
1114-1121
39
Capurro M, Wanless I R, Sherman M. et al .
Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma.
Gastroenterology.
2003;
125
89-97
40
Sung Y K, Hwang S Y, Park M K. et al .
Glypican-3 is overexpressed in human hepatocellular carcinoma.
Cancer Sci.
2003;
94
259-262
41
Hippo Y, Watanabe K, Watanabe A. et al .
Identification of soluble NH 2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma.
Cancer Res.
2004;
64
2418-2423
42
Marrero J A, Romano P R, Nikolaeva O. et al .
GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocullular carcinoma.
J Hepatol.
2005;
43
1007-1012
43
Ishizawa T, Hasegawa K, Aoki T. et al .
Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma.
Gastroenterology.
2008;
134
1908-1916
44
Shirabe K, Shimada M, Gion T. et al .
Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume.
J Am Coll Surg.
1999;
188
304-309
45
Okamoto E, Kyo A, Yamanaka N. et al .
Prediction of the safe limits of hepatectomy by combined volumetric and functional measurements in patients with impaired hepatic function.
Surgery,.
1984;
95
586-592
46
Abdalla E K, Hicks M E, Vauthey J N.
Portal vein embolization: rationale, technique and future prospects.
Br J Surg.
2001;
88
165-175
47
Farges O, Belghiti J, Kianmanesh R. et al .
Portal vein embolization before right hepatectomy: prospective clinical trial.
Ann Surg.
2003;
237
208-217
48
Sasaki A, Iwashita Y, Shibata K. et al .
Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma.
Eur J Surg Oncol.
2006;
32
773-779
49
Helmberger T, Dogan S, Straub G. et al .
Liver resection or combined chemoembolization and radiofrequency ablation improve survival in patients with hepatocellular carcinoma.
Digestion.
2007;
75
104-112
50
Regimbeau J M, Kianmanesh R, Farges O. et al .
Extent of liver resection influences the outcome in patients with cirrhosis and small hepatocellular carcinoma.
Surgery.
2002;
131
311-317
51
Fan S T, Lo C M, Liu C L. et al .
Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.
Ann Surg.
1999;
229
322-330
52
Poon R T, Ng I O, Fan S T. et al .
Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.
J Clin Oncol.
2001;
19
3037-3044
53
Morris-Stiff G, Gomez D, Liguori Carino de N. et al .
Surgical management of hepatocellular carcinoma: Is the jury still out?.
Surg Oncol.
2009;
18
298-321
54
Portolani N, Coniglio A, Ghidoni S. et al .
Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications.
Ann Surg.
2006;
243
229-235
55
Mazzaferro V, Regalia E, Doci R. et al .
Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.
N Engl J Med.
1996;
334
693-699
56
Iwatsuki S, Starzl T E, Sheahan D G. et al .
Hepatic resection versus transplantation for hepatocellular carcinoma.
Ann Surg.
1991;
214
221-228
57
Colella G, Bottelli R, De Carlis L. et al .
Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.
Transpl Int.
1998;
11
193-196
58
Yoo H Y, Patt C H, Geschwind J F. et al .
The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time.
J Clin Oncol.
2003;
21
4329-4335
59
Yao F Y, Ferrell L, Bass N M. et al .
Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria.
Liver Transpl.
2002;
8
765-774
60
Mazzaferro V, Llovet J M, Miceli R. et al .
Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis.
Lancet Oncol.
2009;
10
35-43
61
Decaens T, Roudot-Thoraval F, Bresson-Hadni S. et al .
Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.
Liver Transpl.
2005;
11
767-775
62
Chapman W C, Majella Doyle M B, Stuart J E. et al .
Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation.
Ann Surg.
2008;
248
617-625
63
Ebara M, Okabe S, Kita K. et al .
Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation.
J Hepatol.
2005;
43
458-464
64
Lencioni R, Crocetti L.
Image-guided thermal ablation of hepatocellular carcinoma.
Critical Reviews in Oncology/Hematology.
2008;
66
200-207
65
Lencioni R, Bartolozzi C, Caramella D. et al .
Treatment of small hepatocellular carcinoma with percutaneous ethanol injection. Analysis of prognostic factors in 105 Western patients.
Cancer.
1995;
76
1737-1746
66
Livraghi T, Giorgio A, Marin G. et al .
Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection.
Radiology.
1995;
197
101-108
67
Chen M S, Li J Q, Zheng Y. et al .
A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma.
Annals of Surgery.
2006;
243
321-328
68
Koda M, Murawaki Y, Mitsuda A. et al .
Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma.
Cancer.
2000;
88
529-537
69
Lencioni R A, Allgaier H P, Cioni D. et al .
Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection.
Radiology.
2003;
228
235-240
70
Lin S M, Lin C J, Lin C C. et al .
Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less.
Gut.
2005;
54
1151-1156
71
Shiina S, Teratani T, Obi S. et al .
A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma.
Gastroenterology.
2005;
129
122-130
72
Choi D, Lim H K, Rhim H. et al .
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.
European Radiology.
2007;
17
684-692
73
Lencioni R, Cioni D, Crocetti L. et al .
Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.
Radiology.
2005;
234
961-967
74
Tateishi R, Shiina S, Teratani T. et al .
Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases.
Cancer.
2005;
103
1201-1209
75
Livraghi T, Meloni F, Di Stasi M. 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.
2008;
47
82-89
76
Yin X Y, Xie X Y, Lu M D. et al .
Percutaneous thermal ablation of medium and large hepatocellular carcinoma: long-term outcome and prognostic factors.
Cancer.
2009;
115
1914-1923
77
Marelli L, Stigliano R, Triantos C. et al .
Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.
Cardiovasc Intervent Radiol.
2007;
30
6-25
78
Wang J H, Changchien C S, Hu T H. et al .
The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma – Survival analysis of 3892 patients.
Eur J Cancer.
2008;
44
1000-1006
79
Varela M, Real M I, Burrel M. et al .
Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics.
J Hepatol.
2007;
46
474-481
80
Camma C, Schepis F, Orlando A. et al .
Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials.
Radiology.
2002;
224
47-54
81
Llovet J M, Burroughs A, Bruix J.
Hepatocellular carcinoma.
Lancet.
2003;
362
1907-1917
82
Llovet J M, Real M I, Montana X. et al .
Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.
Lancet.
2002;
359
1734-1739
83
Bruix J, Llovet J M, Castells A. et al .
Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.
Hepatology.
1998;
27
1578-1583
84
Chang J M, Tzeng W S, Pan H B. et al .
Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study.
Cancer.
1994;
74
2449-2453
85
Kawai S, Okamura J, Ogawa M. et al .
Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.
Cancer Chemother Pharmacol.
1992;
31 (Suppl)
1-6
86
Lencioni R, Malagari K, Vogl T. et al .
A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization.
J Clin Oncol.
2009;
27
4523
87
Kulik L M, Carr B I, Mulcahy M F. et al .
Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis.
Hepatology.
2008;
47
71-81
88
Ho S, Lau W Y, Leung T W. et al .
Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer.
Eur J Nucl Med.
1997;
24
293-298
89
Lau W Y, Ho S, Leung T W. et al .
Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres.
Int J Radiat Oncol Biol Phys.
1998;
40
583-592
90
Lau W Y, Ho S, Leung W T. et al .
What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres?.
Hepatogastroenterology.
2001;
48
338-340
91
Sangro B, Bilbao J I, Boan J. et al .
Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma.
Int J Radiat Oncol Biol Phys.
2006;
66
792-800
92
Geschwind J F, Salem R, Carr B I. et al .
Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.
Gastroenterology.
2004;
127
194-205
93
Salem R, Lewandowski R J, Atassi B. et al .
Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.
J Vasc Interv Radiol.
2005;
16
1627-1639
94
Kulik L M, Atassi B, Holsbeeck van L. et al .
Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation.
J Surg Oncol.
2006;
94
572-586
95
Lawrence T S, Robertson J M, Anscher M S. et al .
Hepatic toxicity resulting from cancer treatment.
Int J Rad Oncol Biol Phys.
1995;
31
1237-1248
96
Lawrence T S, Ten Haken R, Kessler M.
The use of 3-D dose volume analysis to predict radiation hepatitis.
Int J Rad Oncol Biol Phys.
1992;
23
781-788
97
Phillips R, Murikami K.
Primary neoplasma of the liver. Results of radiation therapy.
Cancer.
1960;
13
714-720
98
Notsumata K, Okazaki A, Yokohama T.
Radiotherapy for advanced hepatocellular carcinoma.
Acta Hepatol Jpn.
1992;
33
611-616
99
Takagi H, Takayama H, Yamada S.
Radiation therapy to the hepatocellular carcinoma.
Jpn J Gastroenterol.
1989;
86
237-245
100
Tang Z Y.
Treatment of primary liver cancer – with special reference to the east part of china.
Ann Acad Med.
1980;
9
251-262
101
Li B, Yu J, Wang L. et al .
Study of local three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for patients with Stage III hepatocellular carcinoma.
Am J Clin Oncol.
2003;
26
e92-e99
102
Cheng J C, Wu J K, Huang C M. et al .
Dosimetric analysis and comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy for patients with hepatocellular carcinoma and radiation-induced liver disease.
Int J Radiat Oncol Biol Phys.
2003;
56
229-234
103
Guo W J, Yu E X, Liu L M. et al .
Comparison between chemoembolization combined with radiotherapy and chemoembolization alone for large hepatocellular carcinoma.
World J Gastroenterol.
2003;
9
1697-1701
104
Yamada K, Izaki K, Sugimoto K. et al .
Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma.
Int J Radiat Oncol Biol Phys.
2003;
57
113-119
105
Wu D H, Liu L, Chen L H.
Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma.
World J Gastroenterol.
2004;
10
2184-2189
106
Park W, Lim D H, Paik S W. et al .
Local radiotherapy for patients with unresectable hepatocellular carcinoma.
Int J Radiat Oncol Biol Phys.
2005;
61
1143-1150
107
Louafi S, Boige V, Ducreux M. et al .
Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study.
Cancer.
2007;
109
1384-1390
108
Becker G, Allgaier H P, Olschewski M. et al .
HECTOR Study Group. Long-acting octreotide versus placebo for treatment of advanced HCC: a randomized controlled double-blind study.
Hepatology.
2007;
45
9-15
109
Kawata S, Yamasaki E, Nagase T. et al .
Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial.
Br J Cancer.
2001;
84
886-891
110
Abou-Alfa G K, Schwartz L, Ricci S. et al .
Phase II study of sorafenib in patients with advanced hepatocellular carcinoma.
J Clin Oncol.
2006;
24
4293-4300
111
Llovet J M, Ricci S, Mazzaferro V. et al .
Sorafenib in advanced hepatocellular carcinoma.
N Engl J Med.
2008;
359
378-390
112
Cheng A L, Kang Y K, Chen Z. 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
25-34
113
So B J, Bekaii-Saab T, Bloomston M A. et al .
Complete clinical response of metastatic hepatocellular carcinoma to sorafenib in a patient with hemochromatosis: A case report.
Journal of Hematology and Oncology.
2008;
1
18
114
Llovet J, Mena C, Shan M. et al .
Biomarkers predicting outcome of patients with hepatocellular carcinoma: results from the randomized phase III sharp trial.
Hepatology.
2008;
48 (Suppl)
372A (abstract 149)
115
Perforierte Ulzerationen der Speiseröhre und Mediastinitis mit Todesfolge nach Sorafenib (Nexavar).
Deutsches Ärzteblatt.
2009;
106
A476
116
Miller A A, Murry D J, Owzar K. et al .
Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60 301.
J Clin Oncol.
2009;
27
1800-1805
117
Zhu A X, Sahani D V, Duda D G. et al .
Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study.
J Clin Oncol.
2009;
27
3027-3035
118
Siegel A B, Cohen E I, Ocean A. et al .
Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma.
J Clin Oncol.
2008;
26
2992-2998
119
Thomas M B, Chadha R, Glover K. et al .
Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma.
Cancer.
2007;
110
1059-1067
120
Philip P A, Mahoney M R, Allmer C. et al .
Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer.
J Clin Oncol.
2005;
23
6657-6663
121
Zhu A X, Blaszkowsky L S, Ryan D P. et al .
Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma.
J Clin Oncol.
2006;
24
1898-1903
122
Thomas M B, Morris J S, Chadha R. et al .
Phase II Trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma.
J Clin Oncol.
2009;
27
843-850
123
Zhu A X, Stuart K, Blaszkowsky L S. et al .
Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma.
Cancer.
2007;
110
581-589
124
Park B H, Hwang T, Liu T C. et al .
Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial.
Lancet Oncol.
2008;
9
533-542
125
Liu T C, Hwang T, Park B H. et al .
The targeted oncolytic poxvirus JX-594 demonstrates antitumoral, antivascular, and anti-HBV activities in patients with hepatocellular carcinoma.
Mol Ther.
2008;
16
1637-1642
126
Yamasaki S, Hasegawa H, Kinoshita H. et al .
A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.
Jpn J Cancer Res.
1996;
87
206-211
127
Wu C C, Ho Y Z, Ho W L. et al .
Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal.
Br J Surg.
1995;
82
122-126
128
Sala M, Llovet J M, Vilana R. et al .
Barcelona Clínic Liver Cancer Group. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.
Hepatology.
2004;
40
1352-1360
129
Cammà C, Di Marco V, Orlando A. et al .
Treatment of hepatocellular carcinoma in compensated cirrhosis with radio-frequency thermal ablation (RFTA): a prospective study.
J Hepatol.
2005;
42
535-540
130
Zhang Y J, Liang H H, Chen M S. et al .
Hepatocellular carcinoma treated with radiofrequency ablation with or without ethanol injection: a prospective randomized trial.
Radiology.
2007;
244
599-607
131
Lencioni R, Pinto F, Armillotta N. et al .
Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience.
Eur Radiol.
1997;
7
514-519
132
Arii S, Yamaoka Y, Futagawa S. et al .
Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan.
Hepatology.
2000;
32
1224-1229
133
Taniguchi M, Kim S R, Imoto S. et al .
Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma.
World J Gastroenterol.
2008;
14
1997-2002
134
Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire .
A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma.
N Engl J Med.
1995;
332
1256-1261
135
Lo C M, Ngan H, Tso W K. et al .
Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.
Hepatology.
2002;
35
1164-1171
136
Sciarrino E, Simonetti R G, Le Moli S. et al .
Adriamycin treatment for hepatocellular carcinoma. Experience with 109 patients.
Cancer.
1985;
56
2751-2755
137
Lai C L, Wu P C, Chan G C. et al .
Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial.
Cancer.
1988;
62
479-483
138
Lee J, Park J O, Kim W S. et al .
Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.
Cancer Chemother Pharmacol.
2004;
54
385-390
139
Yeo W, Mok T S, Zee B. et al .
A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma.
J Natl Cancer Inst.
2005;
19
1532-1538
140
Yang T S, Lin Y C, Chen J S. et al .
Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma.
Cancer.
2000;
89
750-756
141
Patt Y Z, Hassan M M, Aguayo A. et al .
Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma.
Cancer.
2004;
101
578-586
142
Boige V, Raoul J L, Pignon J P. et al .
Fédération Francophone de Cancérologie Digestive. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03 – 03 trial.
Br J Cancer.
2007;
97
862-867
143
Bruix J, Llovet J M.
Major achievements in hepatocellular carcinoma.
Lancet.
2009;
373
614-616
144
Llovet J M, Bruix J.
Molecular targeted therapies in hepatocellular carcinoma.
Hepatology.
2008;
48
1312-1327
Prof. Dr. Frank T. Kolligs
Medizinische Klinik und Poliklinik II, Klinikum der Universität München, Campus Großhadern
Marchioninistraße 15
81377 München
eMail: fkolligs@med.uni-muenchen.de