Clinical trial NCT02977754: 18F-FDG PET in HCC Patients Candidate to Treatment With Sorafenib
Official title: Exploring the Prognostic Role of 18F-FDG PET/CT Imaging in Patients Affected by Hepatocellular Carcinoma (HCC) and Candidate to Treatment With Sorafenib
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HCC
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2016-11-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a single-center, single-arm study, lasting 36 months including an estimated period of 24 months for the enrolment and max 12 months of follow-up. All patients affected by HCC and referred to our Institution for systemic treatment with sorafenib will be evaluated for enrolment. A minimum number of 10 patients will be considered for the analysis.

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* patients with an histological diagnosis of HCC and scheduled to undergo systemic treatment with sorafenib;
* obtained informed consent

Exclusion Criteria:

* patients age \<18 years
* pregnancy or breast-feeding;
* patients affected by other malignancies within the last 3 years, with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin.

Primary outcomes:
measure: Early change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
timeFrame: Compare 18F-FDG uptake in HCC lesions at baseline and at 24 hours after the first administration of sorafenib.
Secondary outcomes:
measure: Change of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
timeFrame: Compare 18F-FDG uptake in HCC lesions at baseline and 1 week after the first administration of sorafenib.
measure: Predictive role of metabolic characteristics of HCC (i.e. SUVmax, SUVmean, MTV, TLG) lesions under Sorafenib
timeFrame: 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
measure: Prognostic role of metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
timeFrame: Correlate the patterns of 18F-FDG uptake in HCC lesions with progression-free survival (PFS) and overall survival (OS) assessed during a minimun of 12 months of follow up
Other outcomes:
measure: Correlate tumor markers with metabolic characteristics (i.e. SUVmax, SUVmean, MTV, TLG) of HCC lesions under Sorafenib
timeFrame: Correlate the patterns of 18F-FDG uptake in HCC lesions with alpha-fetoprotein (AFP) measured at baseline and after 8 weeks of treatment
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
Study officials:
affiliation: Istituto Clinico Humanitas
name: Egesta Lopci
role: PRINCIPAL_INVESTIGATOR
References:
citation: Castello A, Rimassa L, Personeni N, Pressiani T, Smiroldo V, Lopci E. Metabolic Switch in Hepatocellular Carcinoma Patients Treated with Sorafenib: a Proof-of-Concept Trial. Mol Imaging Biol. 2020 Oct;22(5):1446-1454. doi: 10.1007/s11307-020-01489-6.