Multimetabolic 18F-Fluorodeoxyglucose (FDG) and 18F-Fluorocholine (FCH) Positron Emission Tomography (PET) as an Early Predictive Factor of Overall Survival in Patients With Advanced Hepatocellular Carcinoma Treated With Sorafenib

Hepatocellular carcinoma (HCC) is the third cause of death by cancer. For patients with inoperable advanced HCC, systematic therapy with Sorafenib, a multikinase inhibitor that has both antiangiogenic and antiproliferative effect, is the only therapeutic with proven survival benefits. However, the efficacy of Sorafenib remains inconstant with a media overall survival of 10,7 months and a disease control rate only 35 to 43%; moreover, the overall incidence of treatment-related adverse event is 80%. Thus, it appears essential to find an early and accurate way to determine which patients are best responding to therapy in order to avoid the toxicity and cost of ineffective therapy.

Positron Emission Tomography (PET) with 18F-Fluorodeoxyglucose (FDG) has shown limited performance in the setting of HCC because of lack of sensitivity, in particular for well-differentiated tumours. However FDG uptake is related to proliferation rate and is an efficient marker survival following liver transplantation and selective internal radiation therapy. Moreover, the addition of a dynamic first-pass acquisition to the standard static scan provides better characterization of the tumour by adding information on tumour perfusion.

FCH which reflects lipids metabolism and specifically choline kinase activity, has shown promising results for detection of HCC when compared with FDG alone. Moreover, choline activity is related to a kinase pathway in mammalian cells, which is specifically inhibited by Sorafenib. However FCH uptake remains inconstant in HCC, and is related to tumour differentiation, by opposition to FDG. Therefore, several studies have suggested that combined evaluation of tumour glucose and lipid metabolism could play a complementary role for the evaluation of HCC in the setting of detection, staging and to predict recurrence following surgical resection. Thus, the investigator hypothesize that the combination of FDG and FCH may be the most accurate imaging evaluation of HCC.

Thus the aim of the present study is to determine the predictive performance of survival of lipid and glucose metabolism and perfusion changes during Sorafenib therapy in patients with advanced HCC.


Eligibility Criteria:
Inclusion Criteria:

* Patient older than 18 years
* Inoperable (advanced or metastatic) HCC histologically proven, or diagnosed according to the Barcelona criteria, determined to be candidate for Sorafenib therapy
* Lesion(s) able to be selected as targeted lesion(s) for modified RECIST criteria
* patient ineligible for curative treatment
* Child-Pugh liver function (platelet count superior or equal to 60X1 000 000 000per liter; haemoglobin superior or equal to 8,5g/dl
* Performance status more or equal to 2
* Able to lie still for 45min for PET/CT scanning
* Able to understand and willing to signa written informed consent document
* Affiliated to the French social security social or beneficiary to such a regimen

Exclusion Criteria:

* Uncontrolled intercurrent illness with short-term life-threatening
* Pregnant or nursing woman
* Patient candidate to local/curative therapy of HCC (surgery, radiofrequency, transarterial chemoembolization, other local therapy).
* History of myocardial infarction less than 6 months before inclusion, uncontrolled hypertension, symptomatic congestive heart failure, anti-arrhythmic therapy (other than beta-blockers or digoxine)
* History of digestive bleeding less than 30 days before inclusion
* history of liver transplantation
* Previous treatment including Sorafenib Uncontrolled diabetes History of allergic reactions attributed to compounds of similar chemical or biologic composition to Fluorocholine, 18F-Fluorodeoxyglucose or Sorafenib
* Psychiatric illness/social situations that would limit compliance with the study requirements