Hepatocellular Carcinoma Recurrent, Liver Transplant; Complications
Conditions
Brief summary
Objective of Study: This study will evaluate the heterogeneity and evolution pathway between primary HCC and tumor relapse after liver transplant. According to the Seed-Soil theory, the primary hypothesis of this study is that HCC patients with different molecular-subtype experience altered different pattern of post-transplant recurrence, thus may have altered postoperative Recurrence-Free Survival (RFS). Because the donors' liver construct different microenvironment for CTC(circulating tumor cells) colonization. The investigators design this translational study to ①explore potential high recurrent risk HCC molecular-subtypes which might benefit from neoadjuvant systematic therapy or early adjuvant systematic therapy;②identify the molecular subtype heterogeneity of primary and recurrent HCC to guide the precision medicine.
Detailed description
40 specimens will be obtained from the primary tumor during liver transplant surgery and biopsy/specimens from intrahepatic tumor or lung metastasis when the patients experience postoperative relapse. The molecular-subtype of HCC will be determined via whole exom sequence(WES), immunohistochemistry(IHC) and RNA-Seq.
Interventions
PROCEDUREliver transplant
Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver.
DIAGNOSTIC_TESTctDNA
Circulating Tumor DNA Correlates With Microvascular Invasion and Predicts Tumor Recurrence of Hepatocellular Carcinoma
DIAGNOSTIC_TESTwhole exome sequencing
xome sequencing analysis of liver tumors could reveal mutational signatures associated with specific risk factors of recurrence.
Sponsors
RenJi Hospital
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma; known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not allowed * Patients have post-transplant HCC recurrence(cohort 1), Indication for being an candidate in the waiting list for liver transplant according to multidisciplinary board evaluation(cohort 2) * The time frame between liver transplant and diagnosis of post-transplant HCC recurrence\> 6 months * No prior hepatectomy or systemic therapy or local therapy (TACE etc.)
Exclusion criteria
* History of oncological systemic treatment * early recurrence(\<6 months) * multiple organ transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| molecular-subtype heterogeneity between primary HCC and post-transplant HCC recurrence | up to 2 years | It is defined as the change of HCC molecular subtype by comparing the primary tumor with intrahepatic or intrapulmonary recurrent tumor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| molecular-subtype | up to 2 years | I.Progenitor Type: defined by the transcriptional and protein overexpression of hepatic progenitor markers, inactivating mutations in RPS6KA3 and AXIN1 and hyperphosphorylation of ERK. The main signalling pathways specifically activated in the progenitor subclass are IGF1R and AKT. II.TGFβ-Wnt Type: characterised by activation of both TGFβ and Wnt pathways and an exhausted immune response. Also, an enrichment in TP53 inactivating mutations, amplification of FGF19 and CCND1, as well as frequent activation of pro-survival signalling pathways including cell cycle, mTOR, RAS-MAPK and MET can be detected. III.G4 Type: It frequently harbour a steatohepatitic phenotype, as well as exhibiting activation of the IL6/JAK-STAT pathway. IV.CTNNB1 Type: a subset of HCC harbouring CTNNB1 mutations. TERT promoter mutations are more frequent in this subclass |
| Recurrence-Free Survival (RFS) | up to 3 years | RFS is defined as the time from inclusion to first documentation of disease recurrence (intrahepatic or intrapulmonary) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death) |
Countries
China
Contacts
Primary ContactZijie Zhang
Outcome results
None listed