Drug loaded microspheres for precise transarterial chemoembolisation of hypervascular liver lesions
Three case studies involving drug loaded microspheres for precise transarterial chemoembolisation (PRECISION TACE) of hypervascular liver lesions
Hepatocellular carcinoma (HCC), one of the leading causes of death worldwide with a peak in the Asian countries, is often well advanced at the first clinical manifestation. Without treatment the five year survival rate is poor. The only curative treatment so far is surgery. However, the majority of patients suffer from unresectable HCC at the time of diagnosis. Thus, several treatment strategies have been developed to improve the quality as well as the duration of life of patients suffering from unresectable HCC. Possible treatment options include radiofrequency (RF) ablation, laser interstitial tumourtherapy (LIT), percutaneous alcohol injection (PAI), and transarterial chemoembolisation (TACE).
The rationale for TACE is the fact that primary liver tumours like the HCC predominantly are supplied from branches of the hepatic arteries. Thus, it is possible to achieve a high concentration of antiproliferative drugs within the tumour without causing too extensive damage to the genuine liver parenchyma which has a dual blood supply from the hepatic artery and portal vein. There are many protocols published on which drug to use in conventional TACE (cTACE), however, most protocols use cisplatin, doxurubicin, epirubicin, or mitomycin C, alone or in combination with lipiodol. The major disadvantge of cTACE is that the intratumoural concentration of the drug rapidly decreases by wash out.
Recently, microspheres (DC Bead, Biocompatibles) which can be saturated by the interventional radiologist with antineoplastic drugs like doxo- or epirubicin emerged onto the market. Using these particles provides two major advantages compared to cTACE, a) the drug is released from the particles in the first 10 to 12 days continuously which results in a higher overall intratumoural drug dose over a longer period, and b) the particles, which are available in different sizes, enabling embolisation of specific feeding vessels.
Limitations and Complications
In the last 12 months we treated a total of 16 patients suffering from hypervascular liver lesions (15 x HCC, 1 x Metastases) with drug (Epirubicin, Pfizer) loaded microspheres (DC Bead, Biocompatibles). In all cases a microcatheter was used in order to minimise arterial embolisation of healthy liver tissue. One patient (out of three) suffering from a large multifocal HCC (not shown in the pictured cases) was treated in both liver lobes in one session. For the following 14 days the patient felt ill and complained about pain in the right upper quadrant of the abdomen. The laboratory showed a marked increase in enzymes like bilirubin, alkaline phosphatase, GOT, GPT, as well as an elevated white blood cell count and C-reactive protein. Thus, keeping in mind that TACE is a palliative treatment in patients suffering from large or multifocal HCCs (in contrast to patients suffering from limited disease in whom TACE might be useful for bridging until liver transplantation) we decided that those patients will be treated step by step depending on the extent of the disease.
Multiple embolisations with DC Bead appear to be well tolerated. One patient (72 y) suffering from a diffuse, multifocal HCC has already been treated five times with DC Bead within the last 11 months. So far, the patient responded well. Liver function is stable, the patient gained weight (no ascites!), and the general condition of the patient improved.
Acknowledgements
The authors thank Dr. Peggy Baumann and Christian Davis (both Terumo) for the technical support during the last years.
Case 1: Well defined HCC in the right lobe
Male patient (53 years, HCV positive) with a well circumscribed, hypervascular HCC in the right liver lobe in liver MR (upper left). Angiography with a 4F C2 Cobra catheter (upper middle) confirmed the presence of a hypervascular lesion. After applying 2ml DC Bead (Biocompatibles) loaded with 50mg epirubicin (Pfizer) to the tumour and the surrounding tissue via a 2.7F microcatheter system (Progreat, Terumo) the tumour did not opacify anymore (upper right, lower left). A control CT scan, obtained one day after PRECISION TACE (pTACE) confirmed embolisation of the tumour. The air bubbles within the tumour are regular findings following embolisation with DC Bead and do not represent an infectious complication (lower middle and right).
Case 2: Diffuse/multifocal HCC
Male patient (66 years, HCV positive) suffering from an ill defined, multifocal HCC with tumour nodules mainly in the right lobe but also - to a smaller degree - in the left lobe. CT scans (upper left and middle) showed a mainly hypervascular, multinodular HCC with some necrosis (upper middle). An angiography performed with a 4F C2 Cobra catheter placed in the main hepatic artery confirmed the diagnosis of a large, multinodular HCC. Then, by using a 2.7F microcatheter (Progreat, Terumo) the feeder of the tumour in the right lobe were intubated (lower left) and the tumour was embolized with a total of 4ml DC Bead (Biocompatibles) loaded with 100mg epirubicin (Pfizer). The control angiography confirmed the vascular denudation of the tumour nodules in the right hepatic lobe (lower middle). The nodules in the left lobe were not treated at this session in order not to stress liver function too much at one session. A control CT scan obtained one day after the embolisation confirmed the vascular denudation of the tumour. Like in Case 1 the air bubbles within the tumour are a regular finding following DC Bead embolisation, they are not indicative of an abscess.
Case 3: Metastases from a choroid melanoma
Male patient (53 years, HCV positive) with a well circumscribed, hypervascular HCC in the right liver lobe in liver MR (upper left). Angiography with a 4F C2 Cobra catheter (upper middle) confirmed the presence of a hypervascular lesion. After applying 2ml DC Bead (Biocompatibles) loaded with 50mg epirubicin (Pfizer) to the tumour and the surrounding tissue via a 2.7F microcatheter system (Progreat, Terumo) the tumour did not opacify anymore (upper right, lower left). A control CT scan, obtained one day after pTACE confirmed the embolisation of the tumour. The air bubbles within the tumour are regular findings following embolisation with DC Bead and do not represent an infectious complication (lower middle and right).
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