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Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma

Curator & Reporter: Dror Nir, PhD

Large organs like the liver are good candidates for focused treatment. The following paper:

Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: What is the evidence today?

By Beatrijs A. Seinstra1, et. al. published mid-2010, gives a review of the state-of-the-art of the then available methods for local lesions’ ablation. As far as ablation techniques availability, I have found this review very much relevant to today’s technological reality. It is worthwhile noting that in the last couple of years, new imaging-based navigation and guidance applications were introduced into the market holding a promise to improve the accuracy of administrating such treatment. These are subject to clinical validation in large clinical studies.  From the above mentioned publication I have chosen to highlight the parts discussing the importance of imaging-based guidance to the effective application of localized ablation-type therapies.

The clinical need:

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Primary liver cancer is the sixth most common cancer worldwide with an incidence of 626,000 patients a year, and the third most common cause of cancer-related death [1]. Only 10–15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and shortage of donors.

Immerging solution:

In order to provide therapeutic options for patients with inoperable HCC, several minimally invasive image-guided therapies for locoregional treatment have been developed. HCC has a tendency to remain confined to the liver until the disease has advanced, making these treatments particularly attractive.

Minimally invasive image-guided therapies can be divided into the group of the tumor ablative techniques or the group of image-guided catheter-based techniques. Tumor ablative techniques are either based on thermal tumor destruction, as in radiofrequency ablation (RFA), cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound (HIFU), or chemical tumor destruction, as in percutaneous ethanol injection (PEI). These techniques are mostly used for early stage disease. Image-guided catheter-based techniques rely on intra-arterial delivery of embolic, chemoembolic, or radioembolic agents [22]. These techniques enable treatment of large lesions or whole liver treatment, and are as such used for intermediate stage HCC (Figure 1).

Minimally invasive image-guided ablation techniques and intra-arterial interventions may prolong survival, spare more functioning liver tissue in comparison to surgical resection (which can be very important in cirrhotic patients), allow retreatment if necessary, and may be an effective bridge to transplantation [2327].

During the last 2 decades, minimally invasive image-guided therapies have revolutionized the management of inoperable HCC.

The value of image guidance

Accurate imaging is of great importance during minimally invasive loco-regional therapies to efficiently guide and monitor the treatment. It enables proper placement of instruments, like the probe in case of ablation or the catheter in case of intra-arterial therapy, and accurate monitoring of the progression of the necrotic zone during ablation.

can all be employed. In current clinical practice, placement of the catheter in intra-arterial procedures is usually performed under fluoroscopic guidance, while ablation may be guided by ultrasound, CT or MRI.

  • Ultrasound guidance allows probe insertion from every angle, offers real time visualization and correction for motion artifacts when targeting the tumor, and is low cost. However, the gas created during ablation (or ice in the case of cryoablation) hampers penetration of the ultrasound beams in tissue, causing acoustic shadowing and obscuring image details like the delineation between tumor borders and ablation zone.
  • CT is also frequently used to guide minimally invasive ablation therapy, and is a reliable modality to confirm treatment results. In comparison to US, it provides increased lesion discrimination, a more reliable depiction of ablated/non-ablated interfaces, and a better correlation to pathologic size [28]. However, due to its hypervascularity, small HCCs can only be clearly visualized in the arterial phase for a short period of time. Another disadvantage of CT is the exposure of the patient and physician to ionizing radiation.
  • Combining US imaging for probe placement and CT for ablation monitoring reduces this exposure. At the moment, hybrid systems are being developed, enabling combination of imaging techniques, like ultrasound and CT imaging, thereby improving the registration accuracy during treatment [29]. The interest in MRI-guided ablation is growing, as it produces a high-quality image allowing high-sensitivity tumor detection and accurate identification of the target region with multiplanar imaging.
  • MRI also enables real-time monitoring of the temperature evolution during treatment [3035]. However, MRI is an expensive technique, and MRI-guided ablation is still limited in clinical practice. Currently, the most widely used ablation technique for percutaneous treatment of focal hepatic malignancies is radiofrequency ablation (RFA), which has been shown to be safe and effective for the treatment of early stage HCC [4850]. During RFA, a small electrode is placed within the tumor, and a high-frequency alternating electric current (approximately 400 MHz) is generated, causing ionic agitation within the tissue. ….. Most frequently ultrasound is used for image guidance (Figs. 23), but there are reports of groups who use CT, MRI, or fluoroscopic imaging.
Ultrasound guided RFA. a: HCC lesion in a non-surgical patient pre-treatment (pointed out by arrow). b: Just after start treatment, electrode placed centrally in the tumor. c: Gas formation during ablation causes acoustic shadowing

Ultrasound guided RFA. a: HCC lesion in a non-surgical patient pre-treatment (pointed out by arrow). b: Just after start treatment, electrode placed centrally in the tumor. c: Gas formation during ablation causes acoustic shadowing

Contrast-enhanced CT pre- and post-RFA. Same patient as in Fig. 2. a: Hypervascular lesion (biopsy proven HCC) in right liver lobe (pointed out by arrow) before treatment. b: Ablated lesion directly post ablation, with reactive hyperemia around the RFA lesion

Contrast-enhanced CT pre- and post-RFA. Same patient as in Fig. 2. a: Hypervascular lesion (biopsy proven HCC) in right liver lobe (pointed out by arrow) before treatment. b: Ablated lesion directly post ablation, with reactive hyperemia around the RFA lesion

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Other research papers related to the management of Prostate cancer were published on this Scientific Web site:

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Imaging guided Cancer-Therapy – a Discipline in Need of Guidance.

 Author – Writer: Dror Nir, PhD

The use of imaging in cancer management is broadly established. During the past two decades, advancements in imaging; image quality, precision and reproducibility lead to introduction of localized, minimally invasive treatments of cancer lesions.

 A statement-paper, published online: 17 January 2013: Radiologists’ leading position in image-guided therapy, which presents the thoughts of the Image-Guided Therapy Working Group within the Research Committee of the European Society of Radiology, give hope that the policy-makers in the European radiology society are becoming aware of the need to guide this process.

Although the authors are addressing imaging guided therapy (IGT) in its broad sense, most of their examples are related to treatment of cancer. The main reason for provided for being concerned with what is happening in this domain is: “This means that the planning, performing and monitoring, as well as the control of the therapeutic procedure, are based and dependent on the “virtual reality” provided by imaging investigations.”

The most interesting points raised by the authors are:

 1. The realization that IGT is involving many “non-radiologist”, and this fact cannot be ignored: “This role is mainly driven by the sophisticated opportunities offered by medical computing and radiological image guidance with regard to precision and minimal invasiveness [2]. However, the impact of radiology on the regulatory medico-legal, technical and radioprotection issues in this field have not yet been defined. Since an increasing number of procedures will probably be performed by non-radiologists, several main questions have to be addressed:

  • How should the radiology training requirements for non-radiologists be provided?
  • How should the technical and radioprotection related responsibilities for radiological imaging systems used by non-radiologists be organised?
  • How should radiologists be involved in the practical routine use of non-radiological image-guided procedures in clinical practice?

Considering the almost pan-European medical reality with decreasing staff resources and increasing diversification and subspecialisation, radiologists have to stress the fact that within a cooperative, goal-oriented and multidisciplinary environment, the specialty-specific knowledge should confer upon radiologists a significant impact on the overall responsibility for all imaging-related processes in various non-radiological specialties (such as purchase, servicing, quality management, radiation protection and documentation). Furthermore, radiologists should take responsibility for the definition and compliance with the legal requirements regarding all radiological imaging, especially if non-radiologists have to be trained in the use of imaging technology for guidance of therapy.”

2. Quality assurance and service standards needs to be established; “Performing IGT necessitates specific quality management tools for establishing standards and maintaining levels of excellence…. A European task force group on IGT might be necessary to further develop certification guidelines and establish requirements for IGT practice according to known standards, focused on common recommendations and certification guidelines.”

3. Controlling the process of introducing new medical devices into this niche-market: “IGT research can be broadly divided into two categories, target specific research (e.g. the type of tumour or vascular lesion by imaging biomarkers) and technical research (e.g. evaluation of a new device or procedure). Understanding the efficacy and application of new and emerging technologies is a critical first step, which then leads to target-specific research. The focus of this research is aimed at understanding when, where and in whom the therapy can provide clear clinical benefit and how to use IGT in conjunction with, or as an alternative to, more established therapies. This also clearly includes research on the development and implementation of imaging biomarkers, defined as objectively measured indicators of normal biological processes, pathological changes, or responses to a therapeutic intervention [9]…..

4. An unusual remark is made in respect to the way new devices are introduced: “Clinical specialists who lack the knowledge and expertise required to champion IGT and who are often already over-committed in pursuing their own research goals often dominate committees in control of other funding streams….”

5. Clear recognition that “health-care costs” is of outmost importance: “Demonstration of the cost effectiveness of IGT methods of treatment and targeting with formal quantification of financial as well as patient benefit would encourage their wider adoption. In a broad perspective, health technology assessment (HTA) might be the way for the systematic evaluation of health-relevant IGT procedures and methods, the effectiveness, safety and economic viability of a health intervention, as well as its social, ethical, legal and organisational effects; and for providing a basis for decisions in the health system.”

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