Role of Perfluorobutane in Lesion Detection, Targeting and Response Assessment for Ablation of HCC
Condition: Hepatocellular Carcinoma; Microwave Ablation
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional

Summary: 
      Primary liver cancers are the sixth most common malignancies worldwide, with hepatocellular
      carcinoma (HCC) accounting for approximately 80% of them. The Barcelona Clinic Liver Cancer
      (BCLC) classification is widely used in the management of HCC. At the time of diagnosis,
      fewer than 30% of the patients qualify for resection or transplant due to the large size or
      multiplicity of the lesions, background chronic liver disease, and other comorbidities.

      However, the recent spread of surveillance has led to early detection of hepatocellular
      carcinoma (HCC), and the chance of receiving local treatment has increased. There are several
      options to treat small HCCs, including surgical resection, chemical ablation,
      transplantation, and percutaneous ablation (RFA/MWA).

      Today, percutaneous ablation plays a key role in the treatment of early-stage HCC because it
      is less invasive than surgical resection and has a good efficacy. However, targeting of
      lesions under USG alone may be misleading as there may be an enhancing component which is not
      seen on plain ultrasound. To overcome this problem contrast enhanced ultrasound may be used
      intra-procedurally, however conventional ultrasound contrast agents show washout by 5 minutes
      from the system.

      In this study, the investigators prospectively analyze patients undergoing ablation with the
      help of precise needle placement using a Kupffer phase ultrasound contrast agent
      (perfluorobutane) and their post procedure response assessment.
    

Detailed description: 
      International status:

      Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with
      increasing incidence due to hepatitis B and C viruses . Ultrasound (USG) with, or without
      alpha feto-protein levels is a standard tool for surveillance of HCC. However, it leads to
      suboptimal detection rate and false referrals in the US . Use of an ultrasound contrast agent
      can be helpful in surveillance and diagnosis of focal liver lesions . Second generation
      ultrasound contrast agents like sulfur hexafluoride (SonoVue), perflutren lipid (Definity)
      and perfluorobutane (Sonazoid) are microbubbles composed of a phospholipid shell encompassing
      a low-solubility gas . The characteristic property of Sonazoid is its ability to accumulate
      in the reticuloendothelial system (such as the Kupffer cells in the liver) for a sustained
      period of time (up to 60 mins), which is not seen with other second generation contrast
      agents . Malignant liver lesions do not contain Kupffer cells so these lesions appear
      hypoechoic in the Kupffer phase (10-60 minutes) .

      CEUS has been previously used for targeting of lesions for radiofrequency ablation, however
      the contrast agent used in the study was Definity . CEUS with Sonazoid has been frequently
      used in Japan, South Korea and Norway for diagnosis and surveillance. Diagnosis with Sonazoid
      involves the vascular phase (10 sec to 5 minutes) and the Kupffer phase (10-60 minutes). The
      vascular phase shows the tumor vascularity and the Kupffer phase shows the absence of
      reticuloendothelial cells in the lesion (2-4). In case of a new lesion detected in the
      Kupffer phase or a doubt regarding a previously detected lesion, defect reperfusion imaging
      can be done for confirmation and diagnosis . In a comparison between SonoVue and Sonazoid in
      diagnosis of liver lesions, Sonazoid was not inferior to SonoVue in diagnosis and
      significantly better in detecting lesions during whole liver scanning .

      A study was done using Sonazoid enhanced ultrasound for targeting lesions not detected by
      conventional USG for ablation therapy, and it was found that CEUS detected 97% of the viable
      tumours compared to 83% by conventional USG. Furthermore, 93% of the lesions which were not
      detected on conventional USG were treated successfully using late phase of the contrast agent
      as a guiding tool . However, CEUS using Sonazoid was not used to assess treatment response in
      this study. A meta-analysis assessing the treatment response after radiofrequency ablation of
      HCC using CEUS concluded that technical success was higher with Sonazoid compared to other
      agents .

      National status: A study evaluated the role of CEUS in guiding RFA of HCC, however the
      contrast used was SonoVue and no comparison was made of the post op CEUS with routine 1 month
      imaging .

      The purpose of this study is to evaluate role of perfluorobutane in guiding ablation
      (RFA/MWA) of HCC and to compare treatment response two hours post procedure using the same
      ultrasound contrast agent with routine follow up CT/MRI at 1 month post procedure.

        -  Why this study- Sonazoid is available in only limited countries as of now (Japan, South
           Korea, Norway)

        -  So only limited efficacy studies have been done and none in India.

        -  Also, no study as yet has simultaneously evaluated role of Sonazoid in both lesion
           targeting as well as response assessment.

        -  Hypothesis- Immediate post-procedure CEUS with Sonazoid is not inferior to routine
           contrast CT/MRI at 1 month follow-up for response assessment.
    

Intervention name(s): Perfluorobutane
Intervention type(s): Drug
Intervention description(s): Perfluorobutane enhanced ultrasound will be done prior to ablation of HCC and after 2hours post ablation and comparison will be done with 1 month post procedure CT/MRI
Other intervention name(s): Sonazoid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic