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

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. <b>Methods:</b> 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. <b>Results:</b> 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; <i>P</i> = 0.001], MTV ≥ 18 cm³ [HR, 6.3; 95% CI, 2.1-19.3; <i>P</i> < 0.001], and TLG ≥ 53 [HR, 12.6; 95% CI, 2.9-55.2; <i>P</i> = 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 cm³ on baseline ¹⁸F-FDG PET/CT remained an independent predictor of death (HR, 6.6; 95% CI, 1.7-25.2; <i>P</i> < 0.001). <b>Conclusion:</b> 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.