VETC is an Effective Marker for Postoperative Adjuvant Immunotherapy

A Robust Biomarker of Aggressive HCC and the Response for Adjuvant PD-1 Inhibitors or Combined TKIs Following Liver Resection: Vessels That Encapsulate Tumor Clusters

Vessels that encapsulate tumor clusters (VETC) is an invasive metastatic factor in HCC independent of the epithelial mesenchyme transition (EMT), and VETC-positive patients have a higher rate of postoperative recurrence. However, it is not clear how the surgical prognosis of VETC-positive patients can be improved.

Study Overview

• Status: Completed
• Conditions: Recurrence; HCC
• Intervention / Treatment: Drug: PD-1 monoclonal antibody and lenvatinib

Detailed Description

Previous studies have identified VETC as a new metastatic pattern independent of EMT that may be associated with immunosuppression as well as poor prognosis. Multiple retrospective studies find higher rates of postoperative recurrence, distant metastasis in VETC-positive patients. How to improve surgical prognosis in VETC-positive patients needs to be explored. There is no consensus on postoperative adjuvant therapy for HCC. In recent years, adjuvant immunotherapy (sintilimab) and adjuvant immunotherapy combined with targeted therapy (T+A) have been shown to be effective in improving the surgical prognosis. Therefore, the investigators retrospectively collected three surgical resection cohorts, the surgical resection alone group, the postoperative adjuvant PD-1 monotherapy group, and the postoperative adjuvant PD-1 monotherapy combined with Lenvatinib group, to compare these postoperative adjuvant therapies in a subgroup of VETC patients.

• Study Type: Observational
• Enrollment (Actual): 462

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who met the inclusion and exclusion criteria were retrospectively collected for this study.

Description

Inclusion Criteria:

• Underwent radical hepatectomy
• No preoperative treatment
• Pathological confirmed HCC
• High-risk recurrent HCC
• Not receiving any adjuvant therapy or receiving adjuvant therapy with PD-1 monotherapy or receiving adjuvant therapy with PD-1 monotherapy in combination with Lenvatinib after surgery

Exclusion Criteria:

• Macrovascular invasion
• No available wax blocks
• No complete clinical information

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Liver resection group; No adjuvant therapy after hepatectomy.
Adjuvant PD-1 group; Adjuvant therapy with PD-1 monoclonal antibody after hepatectomy	Drug: PD-1 monoclonal antibody and lenvatinib; Adjuvant PD-1 group: Patient receives first adjuvant PD-1 monoclonal antibody 2-4 weeks postoperatively, 200mg IV over 21 days for 9 cycles. Adjuvant PD-1 plus Lenvatinib group: Patient receives first adjuvant PD-1 monoclonal antibody 2-4 weeks postoperatively, 200 mg IV 21 days for 9 cycles; lenvatinib is initiated orally 2-4 weeks postoperatively for 6 months.
Adjuvant PD-1 plus Lenvatinib group; Adjuvant therapy with PD-1 monoclonal antibody combined with lenvatinib after hepatectomy.	Drug: PD-1 monoclonal antibody and lenvatinib; Adjuvant PD-1 group: Patient receives first adjuvant PD-1 monoclonal antibody 2-4 weeks postoperatively, 200mg IV over 21 days for 9 cycles. Adjuvant PD-1 plus Lenvatinib group: Patient receives first adjuvant PD-1 monoclonal antibody 2-4 weeks postoperatively, 200 mg IV 21 days for 9 cycles; lenvatinib is initiated orally 2-4 weeks postoperatively for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease -free survival	Disease-free survival was defined as defined as the time from enrollment to diagnosis of recurrence or death from any cause.	From date of include in this research until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months

Collaborators and Investigators

• Sponsor: Chen Xiaoping

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: February 3, 2024
• First Submitted That Met QC Criteria: February 3, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 9, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Antibodies; Antibodies, Monoclonal; Lenvatinib
• Other Study ID Numbers: Biomarker1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No