We spoke to Prof. Constantinos Sofocleous to learn more about his presentation at ECIO 2022.
April 24-27 | Vienna, Austria
April 24-27 | Vienna, Austria
April 24-27 | Vienna, Austria
April 24-27 | Vienna, Austria
April 24-27 | Vienna, Austria
Optimal ablation zone assessments
Improved tumour depiction for accurate targeting followed by optimal ablation zone (AZ) and minimal margin (MM) assessments are critical for tumour ablation success and optimization of resulting oncologic outcomes. Thermal ablation (TA), including radiofrequency (RFA) and microwave (MWA) ablation, destroy cancer cells in situ using cytotoxic levels of thermal energy, with minimal risk. Guidelines recommend TA as a stand-alone therapy or in combination with surgery, provided that all visible disease is eradicated. A residual viable tumour (VT) may remain undetected by current imaging, leading to local tumour progression (LTP), and this has limited the widespread use of TA.
MM > 5 mm is the most important technical factor to achieve acceptable local tumour control after TA. Accuracy of AZ assessments, improved sensitivity of MM measurement and prediction of LTP are critical for TA success. Dedicated 3D software has improved sensitivity and discrimination value for the detection of the MM and prediction of LTP, compared to anatomic imaging and manual measurements. Real-time metabolic imaging used for ablation with the “split dose” technique administers 1/3 of the diagnostic FDG dose, sufficient for tumour imaging and targeting; and the remaining 2/3 upon completion of TA, to assess the AZ and detect a hypermetabolic residual tumour. Metabolic imaging surrogates representing residual tumours after ablation have been described and improve the assessment of the AZ. Despite these developments, all imaging techniques carry significant limitations, including those related to reactive hyperaemia or hypermetabolism around the AZ, bleeding, or oedema, especially when used intraoperatively.
A significant limitation of TA compared to resection is the lack of pathological confirmation of complete tumour eradication with sufficient tumour-negative MM. Trying to achieve the surgical standard of pathologic confirmation of complete resection with wide tumour free margins (R0), prior prospective studies performed examinations of biopsy samples obtained from the centre and margin of the AZ immediately following TA of CLM, showing that MM and biopsy of the AZ are independent predictors of LTP. Optimal assessment of the AZ combines multiplanar AZ and MM computations using fusion of real-time metabolic imaging with CECT of the AZ followed by biopsy of the AZ centre and margin with the aid of 3D models and modified metabolic imaging protocols. The addition of biopsy to the imaging assessments decreases the relative uncertainty of MM measurements. Radiologic-pathologic correlations in resected tumours showed that the radiographic AZ lies within 2 mm of the histopathologic AZ. This critical 1–2 mm difference can be easily miscalculated with current imaging techniques, thus an adequate ablation margin can be measured as suboptimal and vice versa. Further improvements in margin calculation are expected through the upcoming “ACCLAIM” multicentre trial that mandates 3D software confirmation of at least a 5mm MM after TA of CLM (NCT05265169).
Recent prospective studies using immediate post-ablation biopsy of the AZ showed that a post ablation tumour positive result is associated with LTP. The inclusion of AZ assessment through biopsy is particularly helpful when the target tumour cannot be ablated with optimal margins of at least 10 mm. Improved local tumour control was documented for biopsy-proven complete ablation with a MM > 5 mm and are comparable to the outcomes reported for MM >10 mm. This introduces an ablation strategy for tumours that cannot be ablated with wide margins due to their location near critical structures including those at risk for post-ablation biliary complications. The addition of recently described fluorescent methods that can offer rapid assessments of tumour cell viability immediately after TA, allow additional ablation decisions intra-procedurally. To address these issues, intraprocedural 3D biopsy guidance and post-ablation tissue evaluation with real-time morphological and viability surrogates are implemented in an NIH-supported (R01 CA240569-01) currently enrolling clinical trial (NCT01494324) designed to use all these developments, aspiring to develop disease and ablation-specific, predictive surrogate image biomarkers. Such developments may allow complete non-invasive optimal assessment of the AZ in the future.
A limitation of post-ablation biopsy is that the specimens may not reflect tumour necrosis or viability within the entire AZ, as is the case with resected tumours.
The impact of TA has been demonstrated in randomized control trials (RCT) showing significantly prolonged survival in the combined therapy arm treated with RFA (±resection) in addition to chemotherapy vs. the group treated by chemotherapy alone. Preliminary results of the COLLISION RCT also indicate similar tumour control and patient survival between the resection and ablation groups. These findings support the value of complete tumour eradication by TA when used with local curative intent.
3D volumetric computation of the AZ and MM, leveraging real-time PET findings, intraoperative fusion and rapid histopathological assessment of the AZ are all steps that confirm complete tumour eradication, optimizing TA as a local cure for liver tumours, like the surgical standard.
Figure 1. Split-dose PET CT guided Ablation
Standard diagnostic FDG activity of 12 mCi administered in 2 aliquots:
-4-mCi within 30–60 minutes before ablation
-8 mCi immediately post-ablation
Figure 2: Use of Pre ablation PET CT and post Ablation CECT for multiplanar/3D AZ assessment and margin calculation
PET image of the tumour (A) fused with CT is used to guide the placement of ablation electrode (white arrows) (B), to segment the tumour and to generate theoretical margins (C). D: Post-TA CE-CT is used to segment the AZ. E and F: Orthogonal views of the fused pre-TA PET and post-TA CE-CT guiding sampling of the tumour region (E) and minimal margin region (F)
Figure 3: Post Ablation Biopsy
The bottom three images on the left show how the fusion of PET with CECT facilitates the centre and margin of the AZ.
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Constantinos T. Sofocleous
Memorial Sloan Kettering Cancer Center
Weill-Cornell Medical College
New York City, NY/USA
Prof. Constantinos Sofocleous is a professor of interventional radiology at the Weill-Cornell imedical college in New York City, and an attending physician in interventional oncology at the Memorial Sloan Kettering Cancer Center. He received his medical education at the University of Athens School of Medicine and completed residencies St. Luke’s-Roosevelt Hospital Center and the Columbia University College of Physicians and Surgeons, as well as an IR fellowship at the NYU Medical Center. Prof. Sofocleous is a CIRSE and SIR fellow, the recipient of multiple awards and an author on more than 200 research publications.He serves in the Executive Council of the SIR as the International Councilor and is one of the Directors at Large of the SIO. He is the Global PI of the recently announced SIO-supported ACCLAIM trial. He serves in the Executive Council of the SIR as the international counsellor and is one of the directors at large of the SIO. He is the Global PI of the recently announced SIO-supported ACCLAIM trial.