Thermal Ablation for Hepatocellular Carcinoma: What's New in 2019

Feipeng Zhu; Hyunchul Rhim

Disclosures

Chin Clin Oncol. 2019;8(6):58 

In This Article

Technical Advancement

Early detection of smaller tumors has increased due to "state-of-the-art" imaging techniques. Magnetic resonance imaging (MRI) with liver-specific contrast agents now allows imagers to evaluate the hepatobiliary phase besides the arterial and portal venous phase similar to conventional extracellular contrast agents. The diagnostic performance of Gd-EOB-DTPA-enhanced MRI with diffusion-weighted imaging for small HCCs, were reported with a sensitivity of 91–93%.[56] Gd-EOB-DTPA-enhanced MRI by adding hypointensity on the hepatobiliary phase can increase sensitivity for diagnosing subcentimeter HCCs.[56–59]

Contrast-enhanced US (CEUS) is also gaining acceptance as a useful imaging tool to diagnose HCC and further characterize indeterminate nodules with equivocal enhancement on CT or MRI. Furthermore, the long temporal window on the post-vascular phase of Sonazoid®-enhanced ultrasound provides improved performance for US guided ablation for HCC. Sonazoid®-enhanced ultrasound can localize the index tumor in over 80% of inconspicuous tumors with fusion imaging[60] (Figure 3). Contrast-enhanced US (CEUS) can be used as an imaging modality for post-ablation assessment after ablation.[61]

Figure 3.

Images from a 55-year-old man with hepatitis B virus-related liver cirrhosis who had previously undergone left hemihepatectomy and percutaneous RFA of HCC. (A) A arterial phase of MRI showed a 7 mm enhancing nodule (arrow) in segment 5; (B) after fusion with MRI, a 7 mm hypoechoic nodule (arrow) could be identified at the corresponding area; (C) on arterial phase after Sonazoid injection, the index nodule showed a strong enhancement (arrow). On post-vascular (Kupffer) phase, it showed a clear hypoechoic defect which means an overt recurrent tumor; (D) on post-vascular phase, RF ablation was performed with accurate targeting for subcentimeter recurrent tumor (arrow). MRI, magnetic resonance imaging; RFA, radiofrequency ablation; HCC, hepatocellular carcinoma.

Fusing imaging systems using a magnetic field generator and position sensor in ultrasound probes are now standard tools for ultrasound-guided HCC ablation. For this reason, an operator can more confidently recognize an inconspicuous tumor on real-time US image by comparing the fused CT/MRI-acquired images along the same sectional plane.[61–64] The detectability for small <2 cm tumors can be increased with reducing the probability of mistargeting by using fusion imaging system.[65] Percutaneous fusion US imaging with MRI was technically feasible in two-thirds of patients with subcentimeter (<1 cm) recurrent HCC, showing 98.4% of technique efficacy.[66] Fusion conventional US combined with Gd-EOB-DTPA-enhanced MRI (hepatobiliary phase) can increase the sensitivity over conventional or CEUS techniques, although small and subcapsular tumors are still difficult to accurately localize due to liver deformation during breathing.[67–69]

Another technological development is electromagnetic (EM) tracking, a system for US guided tumor ablation that has been introduced, but for various reasons, has not increased dramatically in popularity. At present, there are several different types of EM tracking including coaxial system with EM-guiding trocar, detachable EM position sensor at handle of electrode, and disposable EM sensor at active tip of electrode.[70,71]

While radiofrequency energy was the most popular energy source for thermal ablation of HCC in the past decade, its limitations include a smaller ablation volume and the potential risk of heat sink effect from adjacent vessels that can ultimately lead to tumor recurrence. The "no touch" technique, with multiple RF electrodes, is drawing attention by demonstrating favorable outcomes compared to traditional tumor insertion techniques using a single electrode (Figure 4). Furthermore, dual-channel RF generators with high power have also been introduced to the market. Many investigations has been introduced to increase the ablation performance using radiofrequency energy including multiple clustered, multi-tined expandable, cooled-wet perfused, multiple switching systems.[31,33,72] Once such study by Woo et al. reported the favorable local control rate of 89% for small- and medium-sized HCC by using a monopolar, multiple-electrode switching system.[31] In addition, a phase III study using lyso-thermosensitive liposomal doxorubicin with RFA demonstrated the potential to improve survival with RFA dwell time of ≥45 minutes for a solitary lesion. The following OPTIMA study has closed and is awaiting follow-up results.[73]

Figure 4.

Images from a 52-year-old woman with hepatitis B virus-related liver cirrhosis who had previously undergone left lateral hemihepatectomy, TACE and RFA for HCC. (A) A arterial phase of MRI showed a 2.1-cm new enhancing mass (arrow) in segment 8; (B) the index mass (arrows) was clearly seen on planning fusion ultrasound with MRI; (C) multiple monopolar RF electrodes (arrows) were inserted using no-touch techniques and ablated the index tumor (*) for 10 minutes; (D) on immediate post-ablation CT, technical success was achieved with 4-cm ablation zone (arrows) with adequate ablative margin surrounding the index tumor (*). MRI, magnetic resonance imaging; RFA, radiofrequency ablation; HCC, hepatocellular carcinoma.

A third-generation microwave ablation system incorporating antenna cooling and high-power generation is spreading widely around the world. This system provides a larger ablation zone with higher temperatures in a given time period compared to RFA.[74] Several studies report better local tumor control rates over RFA, but the evidence proving clear survival benefit over RFA is currently insufficient. While MWA does have some clear advantages over RFA, including shorter ablation time, less pain and less heat sink effect,[18–26,50,51,75,76] further investigation is warranted to compare RFA with MWA in terms of survival benefit.

Other ablative technologies are used for HCC treatment. Although, cryoablation may be safer for peri-ductal tumors and allows for easy monitoring of the ablation zone during the procedure with an iceball. However, it usually requires multiple applicators for a certain ablation volume, and the clinical outcome evidence over thermal ablation remains limited.[77–79] In addition, irreversible electroporation (IRE) is a promising new ablative technique. It mechanism of action uses high-voltage, low-energy direct current to create nanopores within the cell membrane by passage of electrons through adjacent cells. Although clinical data regarding use of IRE to treat HCC are also very limited, a recent study reported an 18-month recurrence-free survival for patients with unresectable HCCs treated by IRE.[80,81] HIFU treatment is also a well-known, non-invasive technique that has mainly been used for advanced HCC in China. However, it is not as popular because of the longer procedure time and limited therapeutic window caused by the thoracic cage and respiratory motion.[82] One recently introduced ablation technique is histotripsy, which can fractionate tissue through a mechanical, non-invasive ultrasonic ablation process that precisely controls acoustic cavitation while utilizing real-time US guidance.[83]

Research on the relationship between ablation and the immune system continues to emerge as the era of immunotherapy evolves as a new paradigm in the field of oncology. Many recent studies have evaluated immuno-ablation (i.e., abscopal effect) in which the use of ablation technology releases immune-related antigens that evoke a transitional immune response. Several studies have reported the relationship of ablation and ficolin-3, macrophage migration inhibitory factor (MIF), and circulating T-cell subsets.[84–86]

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