Chemoembolisation des hepatozellulären Karzinoms: Welche Faktoren bestimmen Therapieansprechen und Überleben?

Zusammenfassung

Ziel der Studie war die Ermittlung unabhängiger Prognosefaktoren bei Patienten mit hepatozellulärem Karzinom (HCC) und transarterieller Chemoembolisation (TACE). Methodik: Bei 91 Patienten mit irresektablem HCC wurden 269 repetitive TACE mit an Tumorgröße und Leberfunktion angepassten Dosen Epirubicin (40 - 60 mg) und Lipiodol (8 - 12 ml) durchgeführt. Für die Merkmale Tumorgröße, makroskopischer Typ, Lokalisation, Pfortaderinfiltration, Kapselinfiltration, Vaskularisationsgrad, Speichergrad nach erster TACE, Child-Pugh-Stadium und Okuda-Stadium wurde in uni- und multivariaten Varianzanalysen der Einfluss auf die Überlebenszeit geprüft. Ergebnisse: Ein unabhängiger signifikanter Einfluss auf die Überlebenszeit nach TACE ergab sich für die Merkmale Tumortyp (nodulär versus ­infiltrativ; p = 0,008), Tumorgröße (p = 0,01), Child-Pugh-Sta­dium (A versus B; p = 0,02) und Vaskularisationsgrad des HCC (p = 0,04). Bei 57 Patienten mit nodulärem HCC betrug die mediane Überlebenszeit 17,0 Monate und war signifikant größer als bei 32 Patienten mit infiltrativem HCC (7,9 Monate; p < 0,003; 2 Tumoren waren nicht klassifizierbar). Die 1-, 2- und 3-Jahres-Überlebensraten betrugen bei 57 Patienten im Okuda-Stadium I 73, 31 und 8 % und waren signifikant größer als bei 34 Patienten in den Okuda-Stadien II und III (23, 6 und 4 % p < 0,0001). Schlussfolgerung: Tumortyp, Tumorgröße und Zirrhosestadium bestimmen maßgeblich die Prognose der Patienten nach TACE von HCC. Um eine Lebenszeitverlängerung zu erreichen, ist eine geeignete Auswahl der Patienten erforderlich.

Abstract

Purpose: To determine independent prognostic factors influencing the survival of patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). Materials and Methods: Ninety-one patients with unresectable HCC were treated with 269 repetitive TACE. The dosages of epirubicin (40 - 60 mg) and ethiodized oil (8 - 20 ml) were adjusted to tumor size and liver function. The impact of tumor size, macroscopic tumor type, tumor location, portal vein infiltration, capsular infiltration, tumor vascularization, uptake of ethiodized oil within the tumors, Child-Pugh-Class and Okuda-Stage on patient survival were evaluated by means of univariate and multivariate regression analysis. Results: The following independent prognostic factors were found: tumor type (nodular vs. infiltrating, p = 0 008), tumor size (p = 0.01), Child-Pugh-Class (A vs. B; p = 0.02) and grade of tumor vascularization (p = 0.04). In 57 patients with HCC of the nodular type, the median survival time was significant longer than in 32 patients with HCC of the infiltrating type (17.0 months vs. 7.9 months; p < 0.003; 2 tumors could not be classified). The 1-, 2- and 3-year-survival rates were significantly higher in 57 patients with Okuda-Stage I disease, compared to 34 patients with Okuda-Stage II and III disease (73 %, 31 % and 8 % vs. 23 %, 6 % and 4 % p < 0.0001). Conclusions: Tumor type, tumor size and grade of liver cirrhosis have an independent impact on prognosis of patients with HCC treated by TACE. An appropriate selection of patients is necessary to improve patients survival.

Key words

Hepatocellular carcinoma - chemoembolization, transarterial - prognostic factors, independent - regression analysis - multivariate

Literatur

• 1 Bronowicki J P, Vetter D, Dumas F. et al . Transcatheter oily chemoembolization for hepatocellular carcinoma. A 4-year study of 127 French patients.  Cancer. 1994;  74 16-24
• 2 Stefanini G F, Amorati P, Biselli M. et al . Efficacy of transarterial target­ed treatments on survival of patients with hepatocellular carcinoma. An Italian experience.  Cancer. 1995;  75 2427-2437
• 3 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
• 4 Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire . A comparison of Lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma.  N Engl J Med. 1995;  332 1256-1261
• 5 Pelletier G, Roche A, Ink O. et al . A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma.  J Hepatol. 1990;  11 181-184
• 6 Pelletier G, Ducreux M, Gay F. et al . Treatment of unresectable hepatocellular carcinoma with Lipiodol chemoembolization: a multicenter randomized trial.  Groupe CHC J Hepatol. 1998;  29 129-134
• 7 Llovet J M, Real M I, Montana X. et al . Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomized controlled trial.  Lancet. 2002;  359 1734-1739
• 8 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
• 9 Akashi Y, Koreeda C, Enomoto S. et al . Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases.  Hepatology. 1991;  14 262-268
• 10 Hatanaka Y, Yamashita Y, Takahashi M. et al . Unresectable hepatocellular carcinoma: analysis of prognostic factors in transcatheter management.  Radiology. 1995;  195 747-752
• 11 Hsieh M, Chang W, Wang L. et al . Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors.  Cancer Chemother Pharmacol. 1992;  31 (Suppl) S82-85
• 12 Ikeda K, Kumada H, Saitoh S. et al . Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma.  Cancer. 1991;  68 2150-2154
• 13 Shijo H, Okazaki M, Higashihara H. et al . Hepatocellular carcinoma: a multivariate analysis of prognostic features in patients treated with hepatic arterial embolization.  Am J Gastroenterol. 1992;  87 1154-1159
• 14 Ueno K, Miyazono N, Inoue H. et al . Transcatheter arterial chemoembolization therapy using iodized oil for patients with unresectable hepatocellular carcinoma. Evaluation of three kinds of regimens and analysis of prognostic factors.  Cancer. 2000;  88 1574-1581
• 15 Yamamoto K, Masuzawa M, Kato M. et al . Analysis of prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization.  Cancer Chemother Pharmacol. 1992;  31 (Suppl) S77-81
• 16 Yamashita Y, Takahashi M, Koga Y. et al . Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.  Cancer. 1991;  67 385-391
• 17 Farinati F, Maria N, Marafin C. et al . Unresectable hepatocellular carcinoma in cirrhosis. Survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization.  Digestive Diseases and Sciences. 1996;  41 2332-2339
• 18 Llado L, Virgili J, Figueras J. et al . A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization.  Cancer. 2000;  88 50-57
• 19 Mondazzi L, Botelli R, Brambilla G. et al . Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors.  Hepatology. 1994;  19 1115- 1123
• 20 Savastano S, Miotto D, Casarrubea G. et al . Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with Child’s grade A or B cirrhosis.  J Clin Gastroenterol. 1999;  28 334-340
• 21 Calvet X, Bruix J, Gines P. et al . Prognostic factors of hepatocellular carcinoma in the West: a multivariate analysis in 206 patients.  Hepatology. 1990;  12 753-760
• 22 The Liver Cancer Study Group of Japan . Predictive factors for long term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan.  Cancer. 1994;  74 2772-2780
• 23 Carr B. Hepatic artery chemoembolization for advanced stage HCC: experience of 650 patients.  Hepato-Gastroenterol. 2002;  49 79-86
• 24 Takayasu K, Muramatsu Y, Maeda T. et al . Targeted transarterial oily chemoembolization for small foci of hepatocellular carcinoma using a unified helical CT and angiography system: analysis of factors affecting local recurrence and survival rates.  Am J Roentgenol. 2001;  176 681-688
• 25 Kwok P, Lam T, Chan S. et al . A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma.  J Hepatol. 2000;  32 955- 964
• 26 Lopez R R, Pan S H, Hoffman A L. et al . Comparison of transarterial chemoembolization in patients with unresectable, diffuse vs focal hepatocellular carcinoma.  Arch Surg. 2002;  137 653-658
• 27 Vogl T J, Schroeder H, Trapp M. et al . Multisequentielle arterielle Chemoembolisation fortgeschrittener hepatozellulärer Karzinome: Computertomographische Verlaufsparameter zur Beurteilung des Ansprechens auf die Therapie.  Fortschr Röntgenstr. 2000;  172 43-50
• 28 Kantoh T, Abo H, Tomotsu K. et al . Prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial emboliza­tion (TAE) - significance of repetitive therapies and responses to them within 6 months after the first intervention.  Nippion Shokakibyo Gakkai Zasshi. 1993;  90 1416-1426
• 29 Caturelli E, Siena D A, Fusilli S. et al . Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: eval­uation of damage to nontumorous liver tissue-long-term prospective study.  Radiology. 2000;  21 123-128
• 30 Vogl T J, Eichler K, Zangos S. et al . Das hepatozelluläre Karzinom. Rolle der Bildgebung zur Detektion, Therapieplanung und Therapiekontrolle.  Fortschr Röntgenstr. 2002;  174 1358-1368
• 31 Huppert P E, Geißler F, Duda S H. et al . Chemoembolisation des hepatozellulären Karzinoms: computertomographische Befunde und klinische Resultate bei prospektiv repetitiver Therapie.  Fortschr Röntgenstr. 1994;  160 425-432
• 32 Ernst O, Sergent G, Mizrahi D. et al . Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: comparison of planned periodic chemoembolization and chemoembolization based on tumor response.  Am J Roentgenol. 1999;  172 59-64
• 33 Barbara L, Benzi G, Gaiani S. et al . Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival.  Hepatology. 1992;  16 132-137
• 34 Takayasu K, Suzuki M, Uesaka K. et al . Hepatic artery embolization for inoperable hepatocellular carcinoma; prognosis and risk factors.  Cancer Chemother Pharmacol. 1989;  23 (Suppl) S123-125
• 35 Alvarez R, Banares R, Echenagusia A. et al . Factores pronósticos de supervivencia del carcinoma hepatocelular avanzado tras quimioembolización transarterial.  Gastroenterol Hepatol. 2000;  23 153-158