Multi-probe stereotactic radiofrequency ablation (SRFA) with intraprocedural image fusion represents an efficient minimally invasive therapy for hepatocellular carcinoma (HCC), even with tumour sizes larger than 3cm, and without the need to combine its use with additional treatments, concludes Reto Bale (Department of Radiology, Medical University Innsbruck, Innsbruck, Austria) and colleagues, writing in Hepatology.
In their recent single-institution, retrospective study of prospectively collected data, Bale et al found that the stereotactic ablative treatment had a 97.3% success rate, with 183 of 188 treated lesions exhibiting no residual vital tissue post-intervention.
While the authors acknowledge that liver transplantation represents the only curative option for both HCC and underlying chronic carcinogenic liver disease, long waiting lists for transplants mean that tumour progression often advances beyond the conventional transplant criteria, leading to high patient drop-out rates. To remedy this, physicians offer neo-adjuvant locoregional therapy with the aim of down-staging tumours and decreasing the waiting list drop-out rate for liver transplant. However, previous studies have reported that the presence of partial necrosis following locoregional therapy is a major risk factor for tumour recurrence post liver transplantation. Therefore, Bale and co-authors propose SRFA has an alternative option to neo-adjuvant locoregional therapy before liver transplantation. Watch a video of Reto Bale and colleagues performing SRFA here.
A success for image fusion
Typically, radiofrequency ablation (RFA) is the first choice of HCC treatment for very early stage tumours, smaller than 2cm, due to its “great potential for local curative tumour control”, according to the study authors. However, while the therapeutic response in these small tumours is comparable to surgical resection, larger tumour size comes with an attendant increased risk of recurrence in conventional ultrasound- and computed tomography-guided (US- and CT-) single probe RFA. Indeed, univariate analysis has confirmed that increasing size is an indirect predictor of incomplete response to treatment.
Bale and team advocate for the added use of image fusion to lower this risk for larger tumours. The median tumour size in this study was 2.5cm, with the largest being 8cm, and including 52 lesions with a diameter greater than 3cm. Larger needles necessitated the use of more coaxial needles: the median number of needles per lesion was three for all HCCs, but when focusing only on lesions greater than or equal to 3cm in diameter, this number rises to five.
SRFA was able to overcome the “well-known” limitation of US- and CT-guided single-probe RFA. The authors write: “Using the stereotactic approach with intraoperative image fusion even in lesions greater than or equal to 3cm [in diameter], complete tumour cell death was achieved in 50/52 (96.2%) [of lesions]. In contrast to previous reports about conventional RFA, no correlation between residual tumour and tumour size was found (p=0.5)”.
Long-term survival following SRFA of different cancers—cholangiocellular carcinoma, colorectal liver metastases, breast cancer liver metastases, melanoma liver metastases—has previously been found to be comparable to resection. Listing the advantages of image fusion, the investigators write that 3D-navigation systems “allow for a more sophisticated 3D planning of multiple overlapping ablation zones, precise probe placement and intraoperative assessment of the results by means of image fusion”.
They sought to determine if the implementation of high-end stereotactic techniques—the triumvirate of 3D planning, 3D guidance, and image fusion—could improve the results of thermal ablation. Their findings evidenced that this was the case.
Even with the additional efforts related to the stereotactic approach, Bale and co-authors conclude: “In our opinion the results justify specialised training in stereotactic techniques as well as additional costs related to the infrastructure. We therefore encourage other centres to adapt 3D planning, 3D image-guidance and image fusion to improve the outcome of ablation techniques.”
Seventy-six patients with 131 HCCs between them underwent radiofrequency ablation only, while 51 tumours in 16 patients received RFA after unsuccessful transcatheter arterial chemoembolization (TACE). In 125 sessions, five major complications occurred (4% rate), including one event, respectively, of: liver failure, pulmonary embolism, diaphragmatic injury, bleeding, and pleural effusion.
The authors state that the ultimate goal of thermal ablation is “the induction of irreversible tumour cell destruction”. The absence of residual tumour tissue is therefore an indicator of success. In this study, five out of 188 treated lesions evidenced residual tumour tissue; thus, ablative treatment was considered successful in the remaining 183 lesions (97.3%). In a total of four patients, new manifestations of the disease were observed following treatment.
Statistical analysis revealed that recurrence did not correlate with tumour size (p=0.5), tumour stage (p=0.81), location (p=0.61), sex (p=0.32), or age (p=0.8).
The use of TUNEL staining improved the histopathological analysis
The present study offers the largest patient cohort documented in the medical literature where SRFA outcomes have been histopathologically evaluated using TUNEL staining (terminal deoxynucleotidyl transferase dUTP nick end labelling).
Using TUNEL analysis, freshly apoptotic cell areas show a distinct nuclear staining; in more advanced lesions the cytoplasm of the tumour cells depicts a positive reaction as well. In a 2006 study by Adrian Martin (Baylor Regional Transplant Institute, Dallas, USA) and colleagues, a histological examination of explanted livers utilising both H&E (haematoxylin and eosin) and TUNEL staining yielded a 19.6% higher percentage of tumour cell death than when the HCCs were assessed by H&E staining only.
Whenever the viability of the treated HCC could not be ruled out in conventional H&E sections in Bale et al’s analysis, an additional TUNEL assay was performed. The investigators write: “In contrast to previous studies, and most likely due to the additional use of the TUNEL assay, histopathologic examination correlated well with radiologic imaging prior to liver transplant. To the best of our knowledge, these results are superior to all results published so far on conventional thermal ablation, including similar histopathologic studies with additional TUNEL staining”.
For more information on SRFA, Bale encourages “all interested interventional radiologists” to attend the 3rd European School of Interventional Radiology (ESIR) course on “Reliability in Percutaneous Thermal Ablation”, held 12–13 December 2019 in Innsbruck, Austria. He says: “This workshop will cover an SRFA live case, and all relevant topics that are important for successful thermal ablation. An international distinguished faculty will train the participants in sophisticated planning, guidance and image fusion. Register as soon as possible because the number of participants is limited and the last two courses were sold out soon.”