The Society of Interventional Oncology (SIO) has declared Mayo Clinic, Rochester, USA as the first of 10 sites in the USA and Europe approved for enrolment on the society’s primary clinical trial ‘Ablation with Confirmation of Colorectal Liver Metastases (ACCLAIM), Prospective Trial for Microwave Ablation as a Local Cure.’
Constantinos T Sofocleous (Memorial Sloan Kettering Cancer Center, New York, USA), the study’s global primary investigator presented the background to the trial, as well as its aims, to attendees of the SIO 2023 annual scientific meeting (19–23 January, Washington DC, USA). The Mayo Clinic site study investigators include Grant D Schmit as the principal investigator, and Matthew R Callstrom and Anil N Kurup as co-investigators (all Mayo Clinic, Rochester, USA).
ACCLAIM is the first global, prospective trial to use an objective and reproducible technical endpoint in its design, which SIO believes will drive important changes to future colorectal liver metastases (CRLM) treatment guidelines, the society announced in a press release. In this multicentre, international trial, SIO aspires to establish microwave ablation (MWA) as the preferred local curative treatment option for selected CRLM that can be ablated with sufficient margins. The study mandates the use of 3D software to assess the ablation zone and margins and determine if achieving complete margins during an ablation equates to procedural success, where the primary outcome is local tumour progression-free survival at two years post-ablation. This trial is funded through SIO grants from Boston Scientific, NeuWave Medical (part of Ethicon) and Varian (a Siemens Healthineers company). Participants of the trial will have a diagnosis of CRLM for which they would be offered ablation as standard of care. MWA will be performed using a combination of US Food and Drug Administration (FDA)-cleared or CE marked, commercially available MWA system and margin confirmation (visualisation) 3D software. Upon its launch, the ACCLAIM study is expected to have a three-year enrolment period of approximately 275 participants across sites in the USA and Europe.
Speaking at SIO 2023, Sofocleous began by stating his opinion that the ACCLAIM study was “way overdue” as currently, “surgery is the preferred treatment for synchronous and metachronous CRLM”. Hence, posing the rhetorical question “Why do we need the ACCLAIM?”, the presenter answered that the trial aim is “to prove that [MWA] can be the preferred treatment ahead of surgery for selected CRLM that can be ablated with margins, and to create the evidence to support the use of [MWA] for this indication.” Furthermore, Sofocleous emphasised the importance of “standardising ablation treatment” through mandatory steps involved in image-guided thermal ablation for CRLM.
Sofocleous then referred to ablation’s recent past—when confirming the success of ablation margins was not common practice. Recent software developments, namely 3D assessment software, has facilitated the confirmation of margins, the speaker noted, adding that “if we have this ability intraoperatively, as work using 3D software assessments showed, we may [be able] to retreat intraoperatively and avoid local treatment failures.”
Thanks to two National Institutes of Health (NIH) grants, Sofocleous went on to explain how he has been able to interrogate prospectively the efficacy of achieving complete tumour eradication and creating sufficient margins with tissue sampling. “You can document a minimum of 5mm margin with tissue evidence of no residual viable disease at the end of the ablation treatment,” Sofocleous clarified, furthering that this is “regardless of modality or energy” and “biopsy-proven”. Continuing, Sofocleous informed attendees that “comparisons of intraoperative assessments using contrast-enhanced CT (CECT) with the guideline standard of care—assessment at four to eight weeks post-ablation—have shown that the intraoperative CECT assessment yielding margins of less than 5mm is “the most reliable
factor to predict local tumour progression”.
Sofocleous circled back to underline what “ACCLAIM is mandating to do”. Enrolment mandates “immediate 3D software assessments of the ablation zone and margins”, with a need to create an ablation margin of at least 5mm in order to avoid local tumour progression”. Once the 3D assessment has confirmed a margin greater than 5mm, Sofocleous concluded, “we believe that regardless of centre, country, operator, this unified endpoint (of ablation with minimal margin of at least 5mm) will result in high rates of sustained, long-term tumour control.”
The presenter ended by stating that the trial is anticipating opening in 10 centres, and that any FDA- cleared or CE-marked 3D margin assessment software and ablation device is “acceptable” for use in the trial.