PDF herunterladen
Dtsch Med Wochenschr 2013; 138(27): 1425-1430
DOI: 10.1055/s-0033-1343232
Übersicht | Review article
Hepatologie, Onkologie
© Georg Thieme Verlag KG Stuttgart · New York

Aktuelle Therapie des hepatozellulären Karzinoms unter besonderer Berücksichtigung neuer und multimodaler Therapiekonzepte

Current therapy of hepatocellular carcinoma with special consideration of new and multimodal treatment concepts
T. Göbel
1   Klinik für Innere Medizin II – Gastroenterologie, Hepatologie und Diabetologie, Petrus-Krankenhaus Wuppertal
,
D. Blondin
2   Institut für Diagnostische und Interventionelle Radiologie, Heinrich-Heine-Universität Düsseldorf, Medizinische Fakultät
,
F. Kolligs
3   Medizinische Klinik und Poliklinik II, Campus Großhadern, Uniklinik München
,
E. Bölke
4   Klinik für Strahlentherapie und Radioonkologie, Heinrich-Heine-Universität Düsseldorf, Medizinische Fakultät
,
A. Erhardt
1   Klinik für Innere Medizin II – Gastroenterologie, Hepatologie und Diabetologie, Petrus-Krankenhaus Wuppertal
› Institutsangaben
Weitere Informationen

Publikationsverlauf

17. Januar 2013

08. April 2013

Publikationsdatum:
25. Juni 2013 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Die Inzidenz des hepatozellulären Karzinoms (HCC) nimmt weltweit zu, was insbesondere auf einen Anstieg der Hepatitis-C-assoziierten HCC zurückzuführen ist. Bei mehr als 80 % der Patienten entsteht das HCC aus einer Leberzirrhose. Ferner haben mehr als die Hälfte der Patienten zum Zeitpunkt der Erstdiagnose ein weit fortgeschrittenes Child-Pugh- oder Tumorstadium. Nationale und internationale Therapieempfehlungen beruhen auf dem BCLC („Barcelona Clinic for Liver Cancer“) Algorithmus. Abhängig von dem Stadium der Leberfunktion und der Tumorerkrankung empfiehlt dieser die Resektion, Lebertransplantation, Radiofrequenzthermoablation (RFA), transarterielle Chemoembolisation (TACE), systemische Therapie mit Sorafenib oder eine bestmögliche unterstützende Behandlungsmaßnahme (best supportive care), berücksichtigt hingegen weder Kombinationstherapien noch neuere Therapieverfahren. Es gibt jedoch zunehmend Hinweise, dass Kombinationen, z. B. aus Sorafenib mit TACE oder Kombinationen aus verschiedenen lokoregionären Therapien miteinander, eine höhere Effektivität und damit bessere Tumorkontrolle herbeiführen können als monotherapeutische Ansätze. TACE mit Drug Eluting Beads, die selektive interne Radiotherapie (SIRT) oder Mikrowellenablation (MWA) stellen ferner viel versprechende Therapieansätze dar. Patienten mit einem HCC sollten in einem lokalen Tumorboard besprochen werden, um ein optimales und möglichst individuelles Therapieverfahren anzubieten.

Abstract

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide due to the growing number of hepatitis C related HCCs. In more than 80 % of the patients, HCC arises in a cirrhotic liver. Furthermore, more than half of the patients have an advanced Child-Pugh score or an inoperable tumor stage at the initial diagnosis. Recommendations for the treatment of HCC by national and international guidelines rely on the BCLC (“Barcelona Clinic for Liver Cancer“) algorithm. Depending on the stage of liver function and tumor disease it recommends resection, liver transplantation, radiofrequency thermal ablation (RFA), transarterial chemoembolisation (TACE), systemic therapy with sorafenib or best supportive care, but does neither take into consideration combination of therapies nor new therapy modalities. However, there is increasing evidence that combinations i. e. sorafenib with TACE or combination of locoregional techniques enhance effectivity and tumor control compared to monotherapies. TACE with drug-eluting beads, selective internal radiotherapy (SIRT) and new locoregional therapy procedures like microwave ablation (MWA) are further promising therapeutic approaches. Patients with HCC should be discussed in a local tumor board in order to provide the optimal and most individual way of treatment.

Schlüsselwörter

hepatozelluläres Karzinom (HCC) - multimodal - BCLC-Algorithmus - Therapie

Keywords

hepatocellular carcinoma (HCC) - multimodal - BCLC algorithm - therapy

Ergänzendes Material

 

  • Literatur

  • 1 EASL-EORTC. Clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56: 908-943
    PubMedGoogle Scholar
  • 2 Abou-Alfa GK. TACE and sorafenib: a good marriage?. J Clin Oncol 2011; 29: 3949-3952
    CrossrefPubMedGoogle Scholar
  • 3 Abou-Alfa GK, Johnson P, Knox JJ et al. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA 2010; 304: 2154-2160
    CrossrefPubMedGoogle Scholar
  • 4 Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009; 27: 1485-1491
    CrossrefPubMedGoogle Scholar
  • 5 Belghiti J, Carr BI, Greig PD et al. Treatment before liver transplantation for HCC. Ann Surg Oncol 2008; 15: 993-1000
    CrossrefPubMedGoogle Scholar
  • 6 Bonomo G, Pedicini V, Monfardini L et al. Bland embolization in patients with unresectable hepatocellular carcinoma using precise, tightly size-calibrated, anti-inflammatory microparticles: first clinical experience and one-year follow-up. Cardiovasc Intervent Radiol 2010; 33: 552-559
    CrossrefPubMedGoogle Scholar
  • 7 Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
    CrossrefPubMedGoogle Scholar
  • 8 Chen MS, Li JQ, Zheng Y et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 2006; 243: 321-328
    CrossrefPubMedGoogle Scholar
  • 9 Cheng AL, Kang YK, 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
    CrossrefPubMedGoogle Scholar
  • 10 Cheung TT, Ng KK, Chok KS et al. Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes. World J Gastroenterol 2010; 16: 3056-3062
    CrossrefPubMedGoogle Scholar
  • 11 Chua TC, Morris DL. Exploring the role of resection of extrahepatic metastases from hepatocellular carcinoma. Surg Oncol 2012; 21: 95-101
    CrossrefPubMedGoogle Scholar
  • 12 Duffy JP, Vardanian A, Benjamin E et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg 2007; 246: 502-509
    CrossrefPubMedGoogle Scholar
  • 13 Erhardt A, Zhu E, Blondin D et al. [Increasing number and improved survival of patients with hepatocellular carcinoma from 1988 to 2007: data of a German university clinic]. Z Gastroenterol 2011; 49: 720-727
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 14 Guiu B, Deschamps F, Aho S et al. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 2012; 56: 609-617
    CrossrefPubMedGoogle Scholar
  • 15 Hilgard P, Hamami M, Fouly AE et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010; 52: 1741-1749
    CrossrefPubMedGoogle Scholar
  • 16 Honda Y, Kimura T, Aikata H et al. Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. J Gastroenterol Hepatol 2013; 28: 530-536
    CrossrefPubMedGoogle Scholar
  • 17 Huang J, Yan L, Cheng Z et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 2010; 252: 903-912
    CrossrefPubMedGoogle Scholar
  • 18 Ibarra RA, Rojas D, Snyder L et al. Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors. Acta Oncol 2012; 51: 575-583
    CrossrefPubMedGoogle Scholar
  • 19 Jiang W, Zeng ZC. Is It Time to Adopt External Beam Radiotherapy in the NCCN Guidelines as a Therapeutic Strategy for Intermediate/Advanced Hepatocellular Carcinoma?. Oncology 2013; 84 (Suppl. 01) 69-74
    CrossrefPubMedGoogle Scholar
  • 20 Jung SM, Jang JW, You CR et al. Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases. J Gastroenterol Hepatol 2012; 27: 684-689
    CrossrefPubMedGoogle Scholar
  • 21 Kaseb AO, Garrett-Mayer E, Morris JS et al. Efficacy of bevacizumab plus erlotinib for advanced hepatocellular carcinoma and predictors of outcome: final results of a phase II trial. Oncology 2012; 82: 67-74
    CrossrefPubMedGoogle Scholar
  • 22 Kennedy A, Nag S, Salem R et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 2007; 68: 13-23
    CrossrefPubMedGoogle Scholar
  • 23 Kudo M. Radiofrequency ablation for hepatocellular carcinoma: updated review in 2010. Oncology 2010; 78 (Suppl. 01) 113-124
    CrossrefPubMedGoogle Scholar
  • 24 Lammer J, Malagari K, Vogl T 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 2010; 33: 41-52
    CrossrefPubMedGoogle Scholar
  • 25 Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma – a strategy to increase resectability. Ann Surg Oncol 2007; 14: 3301-3309
    Google Scholar
  • 26 Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology 2010; 52: 762-773
    CrossrefPubMedGoogle Scholar
  • 27 Lencioni R, Llovet JM, Han G 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 2012; 30 (Suppl. 04) abstr LBA154^
    PubMedGoogle Scholar
  • 28 Li C, Zhang W, Zhang R et al. Therapeutic effects and prognostic factors in high-intensity focused ultrasound combined with chemoembolisation for larger hepatocellular carcinoma. Eur J Cancer 2010; 46: 2513-2521
    CrossrefPubMedGoogle Scholar
  • 29 Liao GS, Yu CY, Shih ML et al. Radiofrequency ablation after transarterial embolization as therapy for patients with unresectable hepatocellular carcinoma. Eur J Surg Oncol 2008; 34: 61-66
    CrossrefPubMedGoogle Scholar
  • 30 Lin SM, Lin CJ, Lin CC 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
    CrossrefPubMedGoogle Scholar
  • 31 Liu Y, Zheng Y, Li S et al. Percutaneous microwave ablation of larger hepatocellular carcinoma. Clin Radiol 2013; 68: 21-26
    CrossrefPubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37: 429-442
    CrossrefPubMedGoogle Scholar
  • 34 Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907-1917
    CrossrefPubMedGoogle Scholar
  • 35 Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390
    CrossrefPubMedGoogle Scholar
  • 36 Lubienski A, Bitsch RG, Schemmer P et al. [Long-term results of interventional treatment of large unresectable hepatocellular carcinoma (HCC): significant survival benefit from combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) compared to TACE monotherapy]. Rofo 2004; 176: 1794-1802
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 37 Malagari K, Pomoni M, Kelekis A et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2010; 33: 541-551
    CrossrefPubMedGoogle Scholar
  • 38 Marelli L, Stigliano R, Triantos C et al. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev 2006; 32: 594-606
    CrossrefPubMedGoogle Scholar
  • 39 Morimoto M, Numata K, Kondou M et al. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer 2010; 116: 5452-5460
    CrossrefPubMedGoogle Scholar
  • 40 Morse MA, Hanks BA, Suhocki P et al. Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma. Clin Colorectal Cancer 2012; 11: 185-190
    CrossrefPubMedGoogle Scholar
  • 41 Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74-108
    Google Scholar
  • 42 Peng ZW, Zhang YJ, Liang HH et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology 2012; 262: 689-700
    CrossrefPubMedGoogle Scholar
  • 43 Radeleff BA, Stampfl U, Sommer CM et al. [Transarterial ablation of hepatocellular carcinoma. Status and developments]. Radiologe 2012; 52: 44-55
    CrossrefPubMedGoogle Scholar
  • 44 Rampone B, Schiavone B, Martino A et al. Current management strategy of hepatocellular carcinoma. World J Gastroenterol 2009; 15: 3210-3216
    CrossrefPubMedGoogle Scholar
  • 45 Salem R, Lewandowski RJ, Kulik L et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011; 140: 497-507
    CrossrefPubMedGoogle Scholar
  • 46 Sangro B, Carpanese L, Cianni R et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 2011; 54: 868-878
    CrossrefPubMedGoogle Scholar
  • 47 Sherman M. Recurrence of hepatocellular carcinoma. N Engl J Med 2008; 359: 2045-2047
    CrossrefPubMedGoogle Scholar
  • 48 Shibata T, Iimuro Y, Yamamoto Y et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology 2002; 223: 331-337
    CrossrefPubMedGoogle Scholar
  • 49 Shibata T, Isoda H, Hirokawa Y et al. Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment?. Radiology 2009; 252: 905-913
    CrossrefPubMedGoogle Scholar
  • 50 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
    CrossrefPubMedGoogle Scholar
  • 51 Sieghart W, Hucke F, Pinter M et al. The ART of decision making: Retreatment with TACE in patients with hepatocellular carcinoma. Hepatology 2013; doi: DOI: 10.1002/hep.26256. [Epub ahead of print]
    PubMedGoogle Scholar
  • 52 Torzilli G, Palmisano A, Del Fabbro D et al. Contrast-enhanced intraoperative ultrasonography during surgery for hepatocellular carcinoma in liver cirrhosis: is it useful or useless? A prospective cohort study of our experience. Ann Surg Oncol 2007; 14: 1347-1355
    CrossrefPubMedGoogle Scholar
  • 53 Tranchart H, Di Giuro G, Lainas P et al. Laparoscopic resection for hepatocellular carcinoma: a matched-pair comparative study. Surg Endosc 2010; 24: 1170-1176
    CrossrefPubMedGoogle Scholar
  • 54 Ulbrich G, Kölblinger C, Pinter M et al. AVATACE-1 trial: Bevacizumab as inhibitor of collateral tumor-vessel-growth during transarterial chemoembolisation (TACE) for Hepatocellular Carcinoma – a double-blind, randomized, placebo-controlled pilot-trial. Hepatology 2010; 52: 1159A
    PubMedGoogle Scholar
  • 55 Veltri A, Moretto P, Doriguzzi A et al. Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC). Eur Radiol 2006; 16: 661-669
    CrossrefPubMedGoogle Scholar
  • 56 Zhang L, Zhu H, Jin C et al. High-intensity focused ultrasound (HIFU): effective and safe therapy for hepatocellular carcinoma adjacent to major hepatic veins. Eur Radiol 2009; 19: 437-445
    CrossrefPubMedGoogle Scholar
  • 57 Zhang YJ, Liang HH, Chen MS et al. Hepatocellular carcinoma treated with radiofrequency ablation with or without ethanol injection: a prospective randomized trial. Radiology 2007; 244: 599-607
    CrossrefPubMedGoogle Scholar
  • 58 Zhou Y, Zhao Y, Li B et al. Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma. BMC Gastroenterol 2010; 10: 78
    CrossrefPubMedGoogle Scholar
  • 59 Zhu H, Rosmorduc O, Evans J et al. SEARCH: A phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with hepatocelluar carcinoma (HCC). Vienna: ESMO congress; 2012
    PubMedGoogle Scholar
  • 60 Liapi E, Geschwind JFH. Novel local therapies in hepatocellular carcinoma. Clin Liv Dis 2012; 1: 209-211
    CrossrefPubMedGoogle Scholar
  • 61 Santoro A, Rimassa L, Borbath I et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013; 14: 55-63
    CrossrefPubMedGoogle Scholar
  • 62 Shen YC, Hsu C, Chen AL. Molecular targeted therapy for advanced hepatocellular carcinoma: current status and future perspectives. J Gastroenterol 2010; 45: 794-807
    CrossrefPubMedGoogle Scholar
  • 63 Wörns MA, Koch S, Niederle M et al. The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sorafenib. Dig Liver Dis 2013; 45: 408-413
    CrossrefPubMedGoogle Scholar