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Publications

Journal Article Ahead of print

PubMed: 42061943 DOI: 10.2967/jnumed.125.271382

18F-FDG and 18F-Fluorocholine PET as Prognostic Biomarkers in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Prospective Multicenter Study.

J Nucl Med

Authors: Alexandre Cochet, Victor Besson, Aurélie Bertaut, Anaïs Fouquier, Jean-Marc Vrigneaud, Jean-Pierre Bronowicki, Elodie Chevalier, Alexandra Heurgue, Dimitri Papathanassiou, Jean-Frédéric Blanc, Jean-Baptiste Pinaquy, Julie Vincent, Xavier Palard-Novello, Héloïse Bourien, Claire Tabouret-Viaud, Sylvain Manfredi

Affiliations

  • Université Bourgogne Europe, Centre Georges-François Leclerc, Unicancer, Department of Nuclear Medicine, ICMUB, UMR CNRS 6302, Dijon, France;.
  • Université Bourgogne Europe, Centre Georges-François Leclerc, Unicancer, Department of Nuclear Medicine, ICMUB, UMR CNRS 6302, Dijon, France.
  • Université Bourgogne Europe, Centre Georges-François Leclerc, Methodology and Biostatistics Unit, Dijon, France.
  • Department of Gastro-Enterology and Hepatology, University Hospital of Nancy, Nancy, France.
  • Department of Nuclear Medicine, University Hospital of Nancy, Nancy, France.
  • Department of Hepato-Gastro-Enterology, University Hospital of Reims, Reims. France.
  • Department of Nuclear Medicine, Institut Jean Godinot, Reims, France.
  • CRESTIC, University of Reims Champagne-Ardenne, Reims, France.
  • Department of Hepato-Gastro-Enterology, University Hospital of Bordeaux, Bordeaux, France.
  • Department of Nuclear Medicine, University Hospital of Bordeaux, Bordeaux, France.
  • Université Bourgogne Europe, Centre Georges-François Leclerc, Department of Medical Oncology, Dijon, France.
  • CLCC Eugène Marquis, INSERM, LTSI-UMR 1099, University of Rennes, Rennes, France.
  • Department of Medical Oncology, Centre Eugene-Marquis, Rennes, France; and.
  • Université Bourgogne Europe, University Hospital of Dijon, Department of Hepato-Gastro-Enterology, Dijon, France.

Abstract

The aim of this study was to evaluate the clinical significance of studies with dual radiotracers, 18F-FDG and 18F-fluorocholine ( 18F-FCH), performed before and after 1 mo of sorafenib therapy, in patients with advanced hepatocellular carcinoma (HCC) for the prediction of 1-y survival. Methods: Patients with advanced HCC eligible for sorafenib therapy were recruited in the prospective open-label single-arm multicenter PREMETHEP trial (NCT02847468; 6 recruiting centers). Patients had to undergo 18F-FDG and 18F-FCH PET/CT before treatment initiation and 1 mo after to evaluate baseline and residual tumor metabolism. The following parameters were extracted from each scan: the SUV max and tumor-to-normal-liver ratio (TNR) (SUV max of the tumor divided by SUV max of normal liver) for the more significant lesion, and the volumetric parameters of the intrahepatic tumor burden: metabolic tumor volume (MTV), total lesion glycolysis (TLG) for 18F-FDG, and total lesion choline kinase activity for 18F-FCH. The tumor metabolic response (change in SUV max, TNR, MTV, TLG, and total lesion choline kinase activity) was also calculated. Patients were followed during 1 y after treatment initiation. Cox analysis was performed to determine predictors of death. Optimal thresholds for quantitative parameters were determined using logistic regressions with the Youden index method. Results: Among 61 patients included, 36 were considered for final analysis (all male; median age, 70 y). Twenty-one patients died during follow-up. On univariate analysis, a serum albumin level of less than 36 g/L and parameters reflecting high 18F-FDG tumor burden at baseline were significantly associated with death (TNR ≥ 1.5 [hazard ratio (HR), 7.6; 95% CI, 2.2-26.5; P = 0.001], MTV ≥ 18 cm 3 [HR, 6.3; 95% CI, 2.1-19.3; P < 0.001], and TLG ≥ 53 [HR, 12.6; 95% CI, 2.9-55.2; P = 0.002]). In contrast, neither of the 18F-FCH parameters (baseline and follow-up) and clinical data had prognostic significance. On multivariate analysis, an MTV of at least 18 cm 3 on baseline 18F-FDG PET/CT remained an independent predictor of death (HR, 6.6; 95% CI, 1.7-25.2; P < 0.001). Conclusion: Baseline metabolic tumor burden determined with 18F-FDG PET/CT is a strong prognostic biomarker in patients with advanced HCC receiving sorafenib therapy. 18F-FCH PET/CT does not provide additional prognostic information.

MeSH

Choline, Choline Kinase, Carcinoma, Hepatocellular, Neoplasms, Sorafenib, Liver, Biomarkers, Fluorodeoxyglucose F18, Tumor Burden, Nuclear Medicine, Therapeutics