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
CardioVascular and Interventional Radiology, vol. 45, pp. 606–612
Abstract
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. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713 .
Authors 25
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Timo T. M. Oosterveer corresponding Aachen Department of Radiology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. t.t.m.oosterveer@lumc.nl
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Alexander Broersen Aachen Department of Radiology, Leiden University Medical Center Division of Image Processing (LKEB)
Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
Division of Image Processing, Leiden University Medical Center, Leiden, The Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Radiology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Radiology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Hepatobiliary and Pancreatic Surgery, University Medical Center Groningen, Groningen, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands
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University Medical Center Utrecht
Affiliation as printed
Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum
Affiliation as printed
Department of Radiology, Haaglanden Medical Center, Hague, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Affiliation as printed
Dutch Oncology Research Platform, Utrecht, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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Jouke Dijkstra Aachen Department of Radiology, Leiden University Medical Center Division of Image Processing (LKEB)
Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
Division of Image Processing, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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