The Efficiency of Transarterial Chemoembolization with Drug-Eluting Beads in Hepatocellular Carcinoma

Öz

Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new palliative treatment method for patients with hepatocellular carcinoma (HCC). Little is known about the efficiency of DEB-TACE for patients with HCC. The purpose of our study was to evaluate the treatment efficacy (survival rate, tumor response) and safety of DEB-TACE for inoperable HCC and to identify the predictors of survival in patients with unresectable HCC. Twenty-six patients (18 Child-Pugh A, 8 Child-Pugh B) underwent chemoembolization with doxorubicin DEB, including 5 women and 21 men with a mean age of 67.04 years (range 40–86 years). Twenty patients had one DEB-TACE procedure, while the remaining six had two procedures. Overall median survival and survival at 6 and 12 months were calculated. Meanwhile, the response rate was assessed using response evaluation criteria in solid tumors criteria on computed tomography/magnetic resonance imaging at 1 and 6 months. Overall survival rates at 6 months and 1 year from the first administration of doxorubicin DEB-TACE were 80% and 57%, respectively. At 1 and 6 months, objective tumor response rates were 46.2% and 57.1%, respectively. Child-Pugh class, Okuda staging, Cancer of the Liver Italian Programme score, Barcelona Clinic Liver Cancer staging, serum albumin level, Eastern Cooperative Oncology Group performance status, and tumor morphology and volume were found to be prognostic factors for survival. All of the procedures were technically successful, and there were no major complications. Eighteen patients died during the study period and eight survived.Transarterial chemoembolization with DEB is safe and well tolerated in patients with inoperable HCC. Additional prospective randomized controlled studies are required to assess the efficiency of DEB-TACE.

Anahtar Kelimeler

• Hepatocellular carcinoma, drug-eluting beads, transarterial chemoembolization

The Efficiency of Transarterial Chemoembolization with Drug-Eluting Beads in Hepatocellular Carcinoma

Öz

İlaç yüklü partiküllerle yapılan transarteriyel kemoembolizasyon (DEB-TAKE); inoperatif hepatosellüler karsinomun (HCC) paliyatif tedavisinde yeni bir seçenektir. Literatürde HCC’li hastaların tedavisinde DEB-TAKE’nin etkinliği hakkında sınırlı bilgi vardır. Bu çalışmanın amacı inoperatif HCC olgularında DEB-TAKE tedavisinin etkinliğini (sağkalım, tümör cevabı) ve güvenliliğini değerlendirmek; aynı zamanda bu hastalarda DEB-TAKE sonrası sağkalımda prognostik faktörleri belirlemektir. İnoperatif HCC’si olan, 40-86 yaş arası (ort. 67.04) 5’i kadın ,21’i erkek toplam 26 HCC olgusuna (18 Child-Pugh A ve 8 Child-Pugh B) doksorubisin yüklü partikülle kemoembolizasyon uygulandı. 20 hastaya tek, kalan 6 hastaya çift girişim uygulandı. Grupların 6. ve 12. ay ortanca sağkalım süreleri hesaplandı. DEB-TAKE’nin ilk uygulanmasını takiben olguların 6.ay ve 1 yıllık yaşam süreleri sırasıyla %80 ve %57 olarak saptandı. 1. ve 6.ayda objektif tümör yanıt oranları sırasıyla %46.2 ve %57.1 olarak bulundu. Child-Pugh evresi, Okuda evresi, Cancer of the Liver Italian Programme (CLIP) skoru, Barcelona Clinic Liver Cancer (BCLC) evresi, serum albumin seviyesi, Eastern Cooperative Oncology Group (ECOG) performans statüsü (PS), tümör morfolojisi ve hacmi DEB-TAKE sonrası sağkalımda prognostik faktörler olarak saptandı. Bütün girişimler teknik olarak başarıyla tamamlandı ve işleme bağlı majör komplikasyon görülmedi.Takiplerde 18 hasta öldü, 8 hasta yaşamaktadır. Çalışmamız sonucunda inoperatif HCC olgularında DEBTAKE’nin seçilmiş hasta gruplarında güvenli ve iyi tolere edilebilir bir yöntem olduğu sonucuna varılmıştır. Bununla birlikte tedavi etkinliğini değerlendirecek prospektif randomize kontrollü çalışmalara ihtiyaç vardır

Anahtar Kelimeler

• Hepatosellüler karsinom, ilaç yüklü partikül, transarteriyel kemoembolizasyon

Kaynakça

1. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 2010; 7:448–58.
2. Venook AP, Papandreou C, Furuse J, de Guevara LL. The ıncidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 2010; 15:5–13.
3. Bruix J, Sherma M. AASLD Practice Guideline. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53:1020-2.
4. Forner A RM, Rodrigruez de Lope C, Bruix J. Current Strategy for Staging and Treatment: the BCLC Update and Future Prospects Semin Liver Dis 2010; 30:61–74.
5. Huppert P. Current concepts in transarterial chemoem- bolization of hepatocellular carcinoma. Abdom Imaging 2011; 36:677-83.
6. Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology 2010; 52:762-73.
7. Kalva SP, Thabet A, Wicky S. Recent advances in transar- terial therapy of primary and secondary liver malignan- cies. Radiographics 2008; 28:101-17.
8. Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: ef- ficacy and doxorubicin pharmacokinetics. J Hepatol 2007; 46:474–81.

9. Hong K, Khwaja A, Liapi E, et al. New intra-arterial drug delivery system for the treatment of liver cancer: pre- clinical assessment in a rabbit model of liver cancer. Clin Cancer Res 2006; 12:2563–7.
10. Poon RT, Tso WK, Pang RW, et al. A phase I/II trial of che- moembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 2007; 5:1100–18.
11. Okuda K, Ohtsuki T, Obata H, et al. Natural history of he- patocellular carcinoma and prognosis in relation to treat- ment. Study of 850 patients. Cancer 1985; 56:918-28.
12. The Cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and he- patocellular carcinoma. Hepatology 2000; 31:840-5.
13. Bruix J, Sherman M, Llovet JM, et al. Clinical manage- ment of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35:421–30.
14. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:649–55.
15. Padhani AR, Ollivier L. The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diag- nostic radiologists. Br J Radiol 2001; 74:983-6.
16. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statis- tics. CA Cancer J Clin 2005; 55:74-108.
17. Llovet JM, Bruix J. Systematic review of random- ized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37:429–42.
18. Martin RC, Rustein L, Enguix DP, et al. Hepatic arterial in- fusion of Doxorubicin loaded microsphere for treatment of hepatocellular cancer: a multi-institutional registry. J Am Coll Surg 2011; 213:493-500.
19. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodoL chemoembolization for un- resectable hepatocellular carcinoma. Hepatology 2002; 35:1164–71.
20. Marelli L, Stigliano R, Triantos C, et al. Cardiovascular and Inervent Radiol, Transarterial therapy for hepato- cellular carcinoma: which technique is more effective? Asystematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007; 30:6-25.
21. Lewis AL, Gonzalez MV, Lloyd AW, et al. DC bead: in vi- tro characterization of a drug-delivery device for tran- sarterial chemoembolization. J Vasc Interv Radiol 2006; 17:335–42.
22. Malagari K, Alexopoulou E, Chatzimichail K, et al. Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead. Abdom Imaging 2008; 33:512–9.
23. Lammer J, Malagari K, Vogl T, et al. Prospective random- ized 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.
24. Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS. Comparison of conventional transarterial chemo- embolization (TACE) and chemoembolization with doxo- rubicin drug eluting beads (DEB) for unresectable hepato- celluar carcinoma (HCC). J Surg Oncol 2010; 101:476-80.
25. Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS. Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing che- moembolization with doxorubicin drug-eluting beads: a preliminary study. HPB (Oxford) 2010; 12:174-80.
26. Reyes DK, Vossen JA, Kamel IR, et al. Single-center phase II trial of transarterial chemoembolization with drug- eluting beads for patients with unresectable hepatocel- lular carcinoma: initial experience in the United States. Cancer J 2009; 15:526–32.
27. Sadick M, Haas S, Loehr M, et al. Application of DC beads in hepatocellular carcinoma: clinical and radiological re- sults of a drug delivery device for transcatheter super- selective arterial embolization. Onkologie 2010; 33:31-7.
28. Liapi E, Geschwind JF. Intra arterial therapies for hepa- tocellular carcinoma: where do we stand? Ann Surg Oncol 2010; 17:1234-46.
29. Malagari K, Pomoni M, Spyridopoulos TN, et al. Safety Profile of Sequential Transcatheter Chemoembolization with DC Bead: results of 237 hepatocellular carcinoma (HCC) patients. Cardiovasc Intervent Radiol 2011; 34:774-85.
30. Kettenbach J, Stadler A, Katzler IV, et al. Drug-loaded mi- crospheres for the treatment of liver cancer: review of cur- rent results. Cardiovasc Intervent Radiol 2008; 31:468-76.