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
Priv.-Doz. Dr. med. Peter Huppert
Institut für Strahlendiagnostik und Nuklearmedizin, Klinikum Darmstadt
Grafenstraße 9
64283 Darmstadt
Email: PeterHuppert@t-online.de