**4.4 Ultrasound monitoring of systemic therapies**

94 Liver Tumors

Transarterial chemoembolization (TACE) is part of palliative therapies for HCC used in intermediate stages of the disease. It consists of selective angiographic catheterization of the hepatic artery and injection of chemotherapeutic agents (usually adriamycin, but other molecules are currently the subject of clinical trials), followed by embolization of hepatic artery with gelfoam, alcohol or metal rings (Bruix & Sherman, 2005). A similar procedure is transarterial embolization but without chemotherapeutic agents injection, used in the treatment of hypervascular liver metastases. These therapies are based on the predominantly arterial vasculature of HCC and hypervascular metastases, while the remaining liver parenchyma has a dual vascular intake, predominantly portal. Their efficacy is high only for lesions who are hyperenhanced during arterial phase. The role of US is limited in the first few days after the procedure, and refers only to its complications, due to Lipiodol retention mainly intratumoral, but also diffusely intrahepatic. On ultrasound, Lipiodol appears intensely hyperechoic inside the tumor, with significant posterior attenuation which make US examination more difficult. On the other hand, CE-CT is also limited by the presence of Lipiodol (iodine oil), therefore the evaluation of therapeutic efficiency is currently made by indirect assessing Lipiodol binding to the tumor using nonenhanced CT (Maruyama et al, 2008). CE-MRI is not influenced by the presence of Lipiodol, but it is an expensive method and still difficult to reach. Several studies have proved similar efficacy, even superior, of CEUS compared to CE-CT and CE-MRI for the evaluation of post-TACE treatment results, while other studies have shown the limitations of CEUS especially for deep or small lesions. Given the CEUS limitations, currently some authors consider CT as standard method for the evaluation of TACE and local ablative therapies and CEUS and CE-MRI as complementary methods (Lim et al, 2006, Maruyama et al, 2008). Monitoring TACE therapeutic results by contrast imaging techniques is performed as for ablative

**4.3 Ultrasound monitoring of TACE therapy (transarterial chemoembolization)** 

therapies initially after one month then after every 3 months post-TACE.

create a bridge to liver transplantation.

Given that TACE is indicated only for hyperenhanced lesions during arterial phase, CEUS plays a very important role in monitoring the dysplastic nodules to identify the moment when changes occur in arterial vasculature, being able to have an early therapeutic intervention in order to limit tumor progression, to increase patient survival, and thus to

Fig. 14. Small HCC is seen on the left (nodule in nodule). Efficient chemoembolization of the

nodule (right). CEUS examination shows no circulatory signal within the nodule.

Systemic therapies are procedures based on the affinity of certain molecules to inhibit either tumor cell replication or multiplication of neoplastic vasculature (antiangiogenic therapies). They are intravenously administered and are indicated in advanced stages of liver tumor diseases, when there are no other effective therapeutic solutions. Among ultrasound techniques, CEUS is the one that brought a significant benefit not only by increasing the sensitivity and specificity of ultrasound in detecting liver metastases, but also by assessing the efficacy of systemic therapy for HCC and metastases. The method has been adopted by oncologists since 2003, because it involves no irradiation and has no hepatic or renal toxicity, and it is now currently used in tumor therapeutic evaluation (Lassau et al, 2011). It is currently used in large clinical trials aimed at determining the efficacy of different types of anti-angiogenic molecules by quantifying intratumoral perfusion based on the statistical analysis performed using specific software during post-processing in order to assess therapeutic efficacy as early as possible.
