Hepatocellular Carcinoma Growth and Molecular Aggressiveness (UniRer)

"Integrated Molecular/Imaging Technology for Characterization of Biological Aggressiveness of HCC in Patients Candidate to Liver Transplant"

Our long-term objective is to develop a new tool based on a (molecular-biology) integrated imaging technology able to characterize and categorize hepatocellular carcinoma (HCC) patients in need of liver transplant (LT). To this end, our study aims at correlating specific imaging traits and fractional growth of individual tumors collected over a restricted time frame (T0 and at week 7 after first tumor detection), with a "molecular signature", obtained by custom microarray, histochemical and cytokine analysis. This should allow us to translate a series of purely morphologic information into a meaningful pathobiologic data sets. Validation of the integrated molecular-imaging tool will be performed prospectively by correlating the imaging-molecular data with HCC outcome in term of survival and disease-free survival after down staging procedures.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Cirrhosis

Detailed Description

Organ allocation in our region is regulated according to MELD score. Patients with hepatocellular carcinoma (HCC) receive an additional score depending on size of the tumor and the time spent in transplant waiting list. However, the advantage given to these patients is uniform and does not take into account the profound biological heterogeneity of individual HCCs. To make the additional score righteous, the investigators need to identify patients with aggressively growing HCC who require salvage transplantation while those with slow-growing HCC do not deserve the additional score.

All cirrhotics with suspect HCC identified at routine US screening will be therefore enrolled in the prospective imaging and bio-molecular study.

They will be subjected to two computed tomography (CT) exams at 7 weeks interval to define fractional tumor growth and imaging traits, baseline US-guided liver biopsy for microarray and histochemical characterization, serum sampling for cytokine assay. Survival, disease-free survival after downstaging and transplant outcome will be recorded and analyzed in relation with imaging and molecular data. The investigators expect to set up an accurate imaging and molecular diagnostic tool able to identify patients with aggressive HCC requiring urgent access to transplant, reliable in predicting survival, standardisable and not too expensive.

• Study Type: Observational
• Enrollment (Actual): 78

Contacts and Locations

Study Locations

• Italy
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cirrhotic patients, at first diagnosis of HCC and potential liver transplant candidates

Description

Inclusion Criteria:

• Cirrhotic patients at first US identification of a focal lesion compatible with HCC
• Age > than 18 years
• No contraindications to performance of CT
• No contraindications to performance of US-guided liver biopsy

Exclusion Criteria:

Patients will be excluded if

• are unable to give informed consent to the study;
• liver tissue obtained at biopsy is insufficient to perform molecular/histochemical study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Survival will be compared between patients with rapidly and slowly growing HCCs	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to therapy	Response to therapy (liver transplant, resection, TACE) will be compared between rapidly and slowly growing HCCs	2 years

Collaborators and Investigators

• Sponsor: Prof. Facchinetti Fabio

Publications and helpful links

General Publications

• Critelli RM, Milosa F, Romanzi A, Lasagni S, Marcelli G, Di Marco L, Pivetti A, Schepis F, Romagnoli D, Mancarella S, Dituri F, Martinez-Chantar ML, Giannelli G, Villa E. Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV-positive women with hepatocellular carcinoma. Oncol Lett. 2022 Sep 21;24(5):395. doi: 10.3892/ol.2022.13515. eCollection 2022 Nov.
• Villa E, Critelli R, Lei B, Marzocchi G, Camma C, Giannelli G, Pontisso P, Cabibbo G, Enea M, Colopi S, Caporali C, Pollicino T, Milosa F, Karampatou A, Todesca P, Bertolini E, Maccio L, Martinez-Chantar ML, Turola E, Del Buono M, De Maria N, Ballestri S, Schepis F, Loria P, Enrico Gerunda G, Losi L, Cillo U. Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study. Gut. 2016 May;65(5):861-9. doi: 10.1136/gutjnl-2014-308483. Epub 2015 Feb 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: July 29, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (ESTIMATE): August 6, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 2, 2012
• Last Update Submitted That Met QC Criteria: September 29, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: HCC; Computed tomography; Gene expression; Fractional growth
• Additional Relevant MeSH Terms: Behavioral Symptoms; Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Aggression; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 10/08_CE_UniRer