Is 18F-FDG/18F-Choline Dual-Tracer PET Behavior a Surrogate of Tumor Differentiation in Hepatocellular Carcinoma

Abstract

Background: In hepatocellular carcinoma (HCC) setting, 18 F-FDG and 18 F-choline PET/CT radiotracers are classically considered surrogates of the degree of differentiation, a strong predictor of disease recurrence after curative treatment. Because the corresponding level of evidence has never been assessed as primary end point, the aim of this retrospective study was to specifically assess the relevance of 18 F-FDG combined to 18 F-choline PET imaging as a surrogate of tumor differentiation in HCC. Patients and Methods: A total of 49 histologically proven HCCs (46 patients treated by surgery or liver transplantation) with available baseline 18 F-FDG and 18 F-choline PET/CT, dedicated liver contrast-enhanced CT scan, and histological key features were retrospectively reviewed. Hepatocellular carcinoma tumors with well, moderately, and poorly differentiation (grades I, II, and III of the World Health Organization classification) were compared on their PET findings (double-blinded visual analysis and 8 usual semiquantitative metrics) by using nonparametric Kruskal-Wallis analyses of variance. In the case of statistical significance, pairwise post hoc tests with family-wise error rate adjustment were performed. Results: No statistical difference between the grades was observed for any of the patients' or lesions' characteristics ( P > 0.05), except for the macrovascular invasion between the grades I and II (adjusted P = 0.03). None of the PET findings showed statistical difference between the grades, except the tumor-to-background ratio of 18 F-FDG, higher for the grade III compared with grades I (adjusted P = 0.02) and II (adjusted P = 0.01). For less than one third of cases (14 lesions; 28.5%), the regional uptake was judged visually heterogeneous, but none of the related semiquantitative PET metrics were statistically discriminant ( P > 0.05). Conclusions: Contrary to a common belief, 18 F-FDG/ 18 F-choline dual-tracer PET behavior is not a relevant surrogate of tumor differentiation in HCC.Future multitracer PET studies are mandatory to refine our knowledges of their deep biological meaning in this field.