Aerobic glycolysis also called Warburg effect, represents one of the distinctive hallmarks of the malignant cells. Although energetically less efficient than respiration, fermentative metabolism is advantageous for cell growth due to the increased availability of anabolic intermediates and the reduced cell dependence on oxygen. Moreover, by increasing intracellular reducing equivalents and decreasing mitochondria-derived ROS, glycolysis protects malignant cells from oxidant-induced senescence and apoptosis.~In diagnostic imaging, the Warburg effect is visualized thanks to the utilization of ﬂuoro-2-deoxyglucose, a glucose analogue, labeled with the positron emitting nuclide fluoride-18 (18F). F-2-ﬂuoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET) has emerged useful in many tumor types and in HCC can help ruling out extra-hepatic metastases or sites of recurrent disease, and giving prognostic information. Considering the abovementioned premises, the investigators hypothesize a potential use of 18F-FDG PET for the early assessment of sorafenib-induced metabolic shift in HCC, especially in well-differentiated subtypes usually showing an uptake of the tracer not different or at least not sufficiently increased compared to the normal liver.~For these reasons the investigators decided to conduct an explorative study for the assessment of predictive and prognostic role of 18F-FDG PET in patients affected by advanced HCC and candidate to systemic treatment with sorafenib.~The principal objective of this study is to explore the role of 18F-FDG PET in identifying sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease outcome in advanced HCC patients candidate to systemic treatment with sorafenib.~More specifically the investigators will:~compare 18F-FDG uptake in HCC lesions, identified as target lesions (diam. min. 2cm), at baseline, at 24 hours and 1 week after the first administration of sorafenib.~correlate the patterns of 18F-FDG uptake in HCC lesions with objective tumor response assessed 8 weeks after the first administration of sorafenib according to mRECIST criteria.~correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP) variation at baseline, at 24 hours and 1 week after the first administration of sorafenib.~correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS).
The principal objective of this study is to explore the role of 18F-FDG PET in identifying sorafenib-induced metabolic shift in HCC, thus in predicting treatment response and disease outcome in advanced HCC patients candidate to systemic treatment with sorafenib.