Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

PMID: PMID
DOI: DOI
Journal: Cardiovascular and Interventional Radiology
Year of publication: 2022
Page: 45(5):606-612

T.T.M. Oosterveer, G.C.M. van Erp, P. Hendriks, A. Broersen, C.G. Overduin, C.S.P. van Rijswijk, A.R. van Erkel, R.W. van der Meer, M.E. Tushuizen, A. Moelker, M.R. Meijerink, O.M. van Delden, K.P. de Jong, C. van der Leij, M.L.J. Smits, T.A.J. Urlings, J.P.B.M. Braak, E. Meershoek-Klein Kranenbarg, B. van Duijn-de Vreugd, E. Zeijdner, J.J. Goeman, J.J. Fütterer, M.J. Coenraad, J. Dijkstra & M.C. Burgmans

PURPOSE: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy.

MATERIALS AND METHODS: This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan-Meier estimates are used to assess local and overall recurrence, disease-free and overall survival.

DISCUSSION: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success.