Vascular Invasion Signatures in cfDNA Support Re-staging of Liver Cancer

NCT05540925 | Completed DMC

• 1 other identifier: EHBH-MVIPG37
• Study Type: observational
• Target: 286
• Locations: 1 country
• Sites: 1

Brief Summary

Tumor staging system based on clinicopathological charactertics has been used to guide treatment decisions. However, therapeutic outcomes of "early-stage" hepatocellular carcinoma (HCC) differs significantly, which strongly suggests the requirement for a re-staging of early HCC to inform treatment selection more precisely. Microvascular invasion (MVI) reflects malignant biological characteristics of early HCC, and has a potential role of guiding treatment selection. As such, the objective of this study is to investigate preoperative MVI prediction based on MVI-related genomic signatures of cell-free circulating tumor DNA (ctDNA) to establish a re-staging of early HCC. The investigators have detected 37 mutant genes associated with MVI in HCC tumor tissues. In this study, the investigators will design a gene panel based on these mutant genes to perform targeted gene sequencing on preoperatively collected ctDNA to identify genomic signatures associated with MVI. A nomogram to predict MVI before treatment will be generated by incorporating these genomic signatures. Based on a calculated optimal cut-off value of the nomogram, early HCC patients can be re-staged into subpopulations based on the nomogram-predicted risks of MVI. This study will develop a re-staging system of early HCC based on tumor biological charactertics, which is expected to accurately and individually guide treatment decisions and improve long-term survival outcomes.

Conditions

Carcinoma, Hepatocellular; Hepatocellular Cancer; Liver Cancer

Keywords

hepatocellular carcinoma; re-staging; cell-free DNA; microvascular invasion; decision-making

Outcome Measures

Primary Outcomes (2)

• Recurrence-free survival (RFS)

  The time from surgery to the first diagnosis of recurrence or patient death without recurrence

  Between June 2016 and January 2022

• Overall survival (OS)

  The time from surgery to patient death from any cause or the last follow-up

  Between June 2016 and January 2022

Secondary Outcomes (1)

• Local recurrence

  Between June 2016 and January 2022

Study Arms (2)

Low-risk for MVI

Using the sequencing data of cfDNA, a nomogram to predict MVI was constructed using genomic mutations. We designed to stratify early-stage HCC into two sub-stages with nomogram-estimated high or low risks of MVI, respectively, using an optimal cutoff value of 90. The MVI low-risk group refers to patients with score ≤ 90.

Procedure: Liver resection

High-risk for MVI

Using the sequencing data of cfDNA, a nomogram to predict MVI was constructed using genomic mutations. We designed to stratify early-stage HCC into two sub-stages with nomogram-estimated high or low risks of MVI, respectively, using an optimal cutoff value of 90. The MVI low-risk group refers to patients with score \> 90.

Procedure: Liver resection

Interventions

Liver resection PROCEDURE

All patients underwent curative-intent resection for early-stage HCC (a solitary tumor nodule≤5 cm, or multiple nodules≤3, each≤3 cm). We did not take any other intervention. We retrospectively analyzed the prognostic performance of patients with wide (≥1cm) or narrow (\<1cm) resection margin in different groups.

High-risk for MVI; Low-risk for MVI

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A total of 436 patients who underwent surgical resection for early-stage HCC between June 2015 and December 2017 and met the eligibility criteria were prospectively collected. Of these patients, 150 patients who were operated between June 2015 and May 2016 at the Eastern Hepatobiliary Surgery Hospital (EHBH) served as the panel discovery cohort. Paired tumor and adjacent non-tumor tissues from 81 patients were used for WES, and those from another 69 patients were for targeted gene NGS by using a commercial 123-gene-panel to detect MVI-related mutations. Another 286 patients who underwent surgery between June 2016 and December 2017 at multicenters were used in cfDNA testing and proposed a nomogram for re-staging of early HCC. Using clinical data of the 286 patients, we analysed the clinical relevance of the re-staging system in deciding on the optimal extent of surgical resection for HCC.

You may qualify if:

• aged 18-75 years
• histopathologically confirmed HCC
• tumor within the Milan criteria
• Child-Pugh class A of liver function
• curative-intent surgical resection defined as complete removal of macroscopic nodules with microscopic tumor-free resection margins
• complete clinicopathological and follow-up data

You may not qualify if:

• history of other malignancies
• previous anti-cancer treatment
• distant metastasis and major vascular invasion

Sponsors & Collaborators

• Eastern Hepatobiliary Surgery Hospital: lead

Study Sites (1)

Eastern Hepatobiliary Surgery Hospital, Naval Medical University,

Shanghai, Shanghai Municipality, 021, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Tissue sample of 150 HCC patients were used for WES/NGS sequencing to detect of a gene profile related to MVI to generate a gene panel for targeted sequencing of cfDNA. cfDNA sample were used for targeted NGS sequencing with the gene panel.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Hepatectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Feng Shen, MD, PhD

  Eastern Hepatobiliary Surgery Hospital, Naval Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Surgeon

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 15, 2022
• Study Start: January 1, 2022
• Primary Completion: June 1, 2022
• Study Completion: September 1, 2022
• Last Updated: September 19, 2022

Record last verified: 2022-09

Locations

CN (1)