BackgroundPost-operative recurrence remains the strongest prognostic factor of resected hepatocellular carcinoma (HCC), making the accurate selection of patients with curable HCC a crucial issue. PET imaging combining both 18F-FDG and fatty acid synthase (FAS) radiotracers—such as Choline—has shown its interest for the initial staging and therapeutic management of patients with HCC, but its use is still not consensual. Importantly, the very first dual-tracer PET studies suggested 18F-FDG/FAS PET behavior be linked to the degree of differentiation of HCC, a major predictive factor of post-operative recurrence. Although this key molecular imaging concept may impact how dual-tracer PET will be used in early-stage HCC, its level of evidence remains largely unexplored. In this study, we conducted a systematic review of the available evidence-based data to clarify the relevance of dual 18F-FDG/18F-Choline PET in characterizing the degree of differentiation of HCC tumors.MethodsA systematic search of the PubMed/Medline and Embase databases was performed up to November 2021. A systematic review of the dual-tracer 18F-FDG/18F-Choline PET behavior of histology-proven HCC according to their degree of differentiation was conducted. The overall quality of the included studies was critically assessed based on the STROBE guidelines. Information on study date, design, patient cohort characteristics, grade of differentiation of HCC tumors, and the dual-tracer PET behavior per HCC was independently extracted and summarized.ResultsFrom 440 records initially available, 6 full-text articles (99 histology-proven HCC) provided dual-tracer 18F-FDG/18F-Choline PET behavior per HCC tumor grade were included in the systematic review. Based on our analysis, 43/99 HCCs were reported to be well-differentiated, and 56/99 HCCs were reported to be less-differentiated tumors. In the well-differentiated subgroup, more than half were exclusively positive for 18F-Choline (51%), whereas 39% were positive for both 18F-FDG and 18F-Choline. In the less-differentiated subgroup, 37% of HCC patients were positive exclusively for FDG, 36% were positive for both 18F-FDG and 18F-Choline, and 25% were positive exclusively for 18F-Choline.ConclusionThe 18F-FDG/18F-Choline dual-tracer PET behavior of uptake shows high overlap between well- and less differentiated HCC, making the characterization of tumors challenging based on such PET combination alone. Given our growing knowledge of the molecular complexity of HCC, further studies are necessary to refine our understanding of radiotracers’ behavior in this field and improve the usefulness of PET imaging in the clinical decision process of HCC.

PurposeTo determine the characteristics influence of key histological on 18F-fluorodeoxyglucose (18F-FDG) and 18F-choline positron emission tomography (PET) positivity in hepatocellular carcinoma (HCC).Materials and methodsThe 18F-FDG/18F-choline PET imaging findings of 103 histologically proven HCCs (from 62 patients, of which 47 underwent hepatectomy and 15 received liver transplantation) were retrospectively examined to assess the following key histological parameters: Grade, capsule, microvascular invasion (mVI), macrovascular invasion (MVI), and necrosis. Using a ratio of 70/30 for training and testing sets, respectively, a penalized classification model (Elastic Net) was trained using 100 repeated cross-validation procedures (10-fold cross-validation for hyperparameter optimization). The contribution of each histological parameter to the PET positivity was determined using the Shapley Additive Explanations method. Receiver operating characteristic curves with and without dimensionality reduction were finally estimated and compared.ResultsAmong the five key histological characteristics of HCC (Grade, capsule, mVI, MVI, and necrosis), mVI and tumor Grade (I–III) showed the highest relevance and robustness in explaining HCC uptake of 18F-FDG and 18F-choline. MVI and necrosis status both showed high instability in outcome predictions. Tumor capsule had a minimal influence on the model predictions. On retaining only mVI and Grades I–III for the final analysis, the area under the receiver operating characteristic (ROC) curve values were maintained (0.68 vs. 0.63, 0.65 vs. 0.64, and 0.65 vs. 0.64 for 18F-FDG, 18F-choline, and their combination, respectively).Conclusion18F-FDG/18F-choline PET positivity appears driven by both the Grade and mVI components in HCC. Consideration of the tumor microenvironment will likely be necessary to improve our understanding of multitracer PET positivity.

No abstract