TACE with Drug-Eluting Beads in the treatment of HCC in non-surgical patients

Interventional oncology is one of the fastest growing fields of interventional radiology, with advances in less invasive treatments proving to be effective in destroying cancerous tumours, improving patient care, and also offering the potential to reduce overall healthcare costs and improved quality of life. Cancer treatments in the past relied almost entirely on surgical resection, systemic chemotherapy and radiation therapy. Now, due to medical imaging, the combination of new devices and innovative techniques has led to the evolution of new treatment options.

Transarterial chemoembolisation (TACE) is a minimal invasive procedure that has demonstrated the ability to reduce systemic toxicity, increase local effects and improve overall therapeutic results, particularly in the treatment of unresectable hepatocellular carcinoma (HCC). DC Bead™ (Biocompatibles UK Ltd), has recently emerged as a novel product specifically designed for TACE, which has significantly enhanced local tumour drug concentration without increasing toxicity, in the treatment of such cancers as HCC and hepatic metastases of the colon.

At the recent Cardiovascular and Interventional Radiological Society of Europe (CIRSE) meeting, held in Athens, Greece from September 8-12, 2007, Biocompatibles and Terumo co-hosted a satellite symposium that addressed the future prospects in oncology treatment using Biocompatible’s Drug-Eluting Bead (DEB).

Chaired by Professor Tony Watkinson, Royal Devon and Exeter, UK, the well attended symposium began with Dr Katerina Malagari, University of Athens, Greece, who assessed the safety and efficacy of doxorubicin loaded DC Bead in the treatment of unresectable HCC in cirrhotic patients. She began by explaining the anti-tumoural effect of doxorubicin loaded DC Bead and referred to two studies that examined tumour necrosis rates with several embolic materials (Hong et al. Clin Cancer Res; 2006; and Lewis et al. JVIR 2006).

Hong and colleagues demonstrated that tumour necrosis in the Vx-2 animal model approached 100% at seven days, while plasma concentration of doxorubicin was minimal. In this study, it was found that intra-tumoural doxorubicin levels at 72 hours after embolisation were about 400% higher compared to conventional TACE.

Meanwhile, Lewis et al. showed that induced necrosis was found to emit outwards, centred on clusters of DC Bead. Tumour necrosis was greatest at seven to 14 days after treatment, and for this period the combined damage and necrotic cells approached 100%. The authors also showed that other embolic materials such as the Contour SE Microspheres (Boston Scientific), Embospheres (Biosphere Medical) and Bead Block (Biocompatibles), did not have the ability to uptake and release doxorubicin to the same extent as DC Bead in conditions simulating intra-arterial delivery.

Athenian Registry
Malagari then presented the mid-term results from the 62-patient Athenian Registry. The purpose of the study was to assess the safety and efficacy of doxorubicin loaded DC Bead in the treatment of unresectable HCC in cirrhotic patients. A total of 62 cirrhotic patients with underlying hepatitis infection (HBV or both HBV and HBC) and documented unresectable HCC of 3-10cm in diameter (mean 6.2) were enrolled prospectively in the single centre, single arm study, between December 2004 and March 2006. Patient follow-up was concluded in August 2007 (32 months).

Patients were treated by selective or super-selective embolisation using two different sizes of DC Bead; 100-300µm and/or 300-500µm. DC Bead were loaded with 37.5mg/mL of doxorubicin and each patient received 150mg of the drug, loaded in two vials of DC Bead. The inclusion/exclusion criteria are shown in Table 1.

Procedure
Embolisation was performed at baseline and then every three months if required. The number of procedures for each patient ranged from one to four within the study period. The total number of procedures was 196, and response to each treatment was measured according to the European Association for the Study of the Liver (EASL) assessment criteria. All patients received antibiotic prophylaxis and pain was controlled individually.

Prior to embolisation, angiography of the hepatic artery was performed to map liver vascular anatomy, check for arteriovenous shunts, and identify arterial feeders of the tumour. Computed tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced ultrasound (CEUS) were also used in the study.

Results and survival rates
The survival rates for the Athenian Registry are shown in Table 2. The data clearly demonstrates the clinical effectiveness of the DC Bead technology over a considerable time period (12-32 months), with survival rates of 97.5% (12 months) to 88.2% (32 months). In addition, she commented that these results compare favourably to conventional TACE. In the two decisive randomised control trials (RCTs) that documented a clear benefit of TACE compared to symptomatic treatment, survival rates were substantially lower. In the RCT conducted by Lo et al., one, two, and three year survival rates of 57%, 31% and 26% in the TACE arm were reported, while in the RCT of Llovet et al., survival rates at one and two years were 82% and 63% in the TACE group. Similarly, a French multi-centre trial assessing advanced HCC showed survival rates with TACE of 64% and 38% at one and two years in the TACE group of patients (Table 2).

Malagari also commented on tumour response results in regard to complete and partial response rates, as well as stable disease and progressive disease. She explained that similarly, high percentages of complete response were observed in the study of Varela et al., adding that a valid comparison with previously reported data is difficult due to the in homogeneity in patient selection, chemotherapeutic agents and reporting criteria. However, she stated that until now published response rates with conventional TACE (not using DC Bead) were substantially lower with a mean complete response of 6% and a mean partial response of 26.9% (range 15-55%).

Malagari then presented a series of selected cases demonstrating pre-embolisation and post-embolisation results (Figure 1). She also showed the results of tumour shrinkage from baseline and at follow-up after the second and third treatments.

Conclusions
In summary, Malagari said that the results from the Athenian registry showed that the DC Bead is efficient and effective in treating patients with non-resectable HCC; with high rates of tumour shrinkage, minimal complications and increased mid-term survival.