Gadoxetic acid uptake as a molecular imaging biomarker for sorafenib resistance in patients with hepatocellular carcinoma: a post hoc analysis of the SORAMIC trial.

Osman Öcal, Daniel Rössler, Antonio Gasbarrini, Thomas Berg, Heinz-Josef Klümpen, Irene Bargellini, Bora Peynircioglu, Otto van Delden, Christian Schulz, Kerstin Schütte, Roberto Iezzi, Maciej Pech, Peter Malfertheiner, Bruno Sangro, Jens Ricke, Max Seidensticker

Journal: Journal of cancer research and clinical oncology 2022;148(9):2487-2496

PMID: 34541612

Abstract

PURPOSE

Gadoxetic acid uptake on hepatobiliary phase MRI has been shown to correlate with ß-catenin mutation in patients with HCC, which is associated with resistance to certain therapies. This study aimed to evaluate the prognostic value of gadoxetic acid uptake on hepatobiliary phase MRI in patients with advanced HCC receiving sorafenib.

METHODS

312 patients with available baseline hepatobiliary phase MRI images received sorafenib alone or following selective internal radiation therapy (SIRT) within SORAMIC trial. The signal intensity of index tumor and normal liver parenchyma were measured on the native and hepatobiliary phase MRI images, and relative tumor enhancement higher than relative liver enhancement were accepted as high gadoxetic acid uptake, and its prognostic value was assessed using univariate and multivariate Cox proportional hazard models.

RESULTS

The median OS of the study population was 13.4 (11.8-14.5) months. High gadoxetic acid uptake was seen in 51 (16.3%) patients, and none of the baseline characteristics was associated with high uptake. In univariate analysis, high gadoxetic acid uptake was significantly associated with shorter overall survival (10.7 vs. 14.0 months, p = 0.005). Multivariate analysis confirmed independent prognostic value of high gadoxetic acid uptake (HR, 1.7 [1.21-2.3], p = 0.002), as well as Child-Pugh class (p = 0.033), tumor diameter (p = 0.002), and ALBI grade (p = 0.015).

CONCLUSION

In advanced HCC patients receiving sorafenib (alone or combined with SIRT), high gadoxetic acid uptake of the tumor on pretreatment MRI, a surrogate of ß-catenin mutation, correlates with shorter survival. Gadoxetic acid uptake status might serve in treatment decision-making process.

© 2021. The Author(s).

Address: Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.; Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.; Fondazione Policlinico Gemelli IRCCS, Università' Cattolica del Sacro Cuore, Roma, Italy.; Klinik Und Poliklinik Für Gastroenterologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Leipzig, Germany.; Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Department of Vascular and Interventional Radiology, University Hospital of Pisa, Pisa, Italy.; Department of Radiology, Hacettepe University, Ankara, Turkey.; Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany.; Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University, Magdeburg, Germany.; Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Di Radiologia, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy.; Departments of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany.; Liver Unit, Clínica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.; Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany. [email protected].
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