18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma

Abstract

Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.

Predicting tumor recurrence using metabolic indices of 18F‑FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma

“…Emerging evidence indicates that the Milan criteria and radiographic up-to-seven (UTS) criteria (17), are too restrictive as selection tools for liver transplantation candidates, and therefore, it is necessary to expand these criteria (18,19). Some expanded criteria, based on tumor number and size, such as the UCSF criteria (20) or the Hangzhou criteria (21), revealed that selected patients had a similar prognosis profile compared with those who met the Milan criteria.…”

“…Based on the findings of the presents study, a PET/CT examination prior to LT in all patients is recommended in order to preclude those with extrahepatic metastasis. The following metabolic criteria provide an indication for the order of priority of candidates for OLT: i) Patients with PET-negative imaging should be indicated for OLT regardless of the size and number of tumors; ii) patients meeting the Milan criteria with low metabolic indices should undergo OLT; iii) patients not meeting the Milan criteria with low metabolic indices should be considered for OLT; iv) patients meeting the Milan criteria but with high metabolic burden should undergo TACE to decrease metabolic burdens prior to LT; and v) patients not meeting the Milan criteria with high metabolic indices should be precluded or re-evaluated following treatment to decrease metabolic burden (19). Moreover, a PET/CT examination is strongly recommended within 3 months of OLT in patients with high metabolic indices who received OLT, to detect early recurrence for timely therapy.…”

18f-FDG Pet/Ct as an Assessment Tool of Hepatocellular Carcinoma Secondary to Non-Alcoholic Fatty Liver Disease Development in Experimental Model

“…Though the PET is not recommended as a diagnostic tool in HCC detection, it has already been demonstrated that can be useful to detect metastasis, evaluate treatment response and staging to better therapeutic decision and prognostic (25) . Sugiyama et al demonstrated that 18 F-FDG PET sensitivity in extra-hepatic detection of HCC metastasis is 83% (26) .…”

Microvascular Invasion in HCC: The Molecular Imaging Perspective

“…From these two values, they obtained a tumour-to-liver ratio (SUVT/L) for each lesion. Finally, Kornberg et al compared any significantly enhanced 18F-FDG uptake focus to normal adjacent liver tissue and in a direct approach a tumor to nontumor SUVmax higher than 1 defined a positivity status for HCC of PET scan [ 16 ].…”

“…In this context, nuclear medicine radically changed the decisional algorithm of almost any neoplasm as it allows an in vivo assessment of tumor metabolism [ 15 ]. In fact, with respect to HCC, despite having a lower sensitivity compared to other types of solid tumors, 18 F-fluorodeoxyglucose positron emission tomography with computed tomography ( 18 F-FDG PET/CT) is capable of reflecting glucose tumor metabolism, and it is used in clinical practice as a useful diagnostic tool for staging or restaging, prognostic stratification, and follow-up purposes [ 16 ]. Unfortunately, 18 F-FDG PET/CT has two main drawbacks related to the highly variable tracer uptake in HCC and the relatively high physiological liver uptake, which limits its use for primary diagnosis [ 17 ].…”