Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT06461936 |
Other study ID # |
PrecisionAT |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
January 1, 2019 |
Est. completion date |
April 30, 2025 |
Study information
Verified date |
June 2024 |
Source |
Tongji Hospital |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
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.
Description:
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, with the number of new cases
and deaths increasing yearly. Curative surgery continues to be the preferred treatment for
early-stage HCC. However, some early-stage HCC often experience early recurrence after
surgery, and one of the most common risk factors is microvascular invasion (MVI).
Nevertheless, the overall prognosis of some MVI-negative patients is also not satisfactory.
Whether there are other hidden robust risk factors for recurrence is of intense interest to
clinical scientists.
In contrast to the classic capillary pattern, cobweb-like pattern of vascular is present in
renal cell carcinoma, thyroid follicular carcinoma and HCC. Specifically, this particular
vascular pattern is a continuous lining of sinusoid-like vessels that isolate and encapsulate
individual tumor clusters, and Fang et al. named it vessels that encapsulate tumor clusters
(VETC). CD34 or CD31 immunohistochemical staining of tumor tissue can easily identify the
vascular pattern of VETC, which can exist at any stage of HCC, accounting for about
40%-50.6%. VETC could directly invade adjacent vascular and migrate as tumor clusters instead
of epithelial-mesenchymal transition pathway, which may well explain why VETC-positive HCC is
closely associated with higher postoperative recurrence rate and poor prognosis. Due to the
high proportion of VETC vascular patterns and poor prognosis, it is necessary to adopt
effective adjuvant treatment. Zhuan et al found that unresectable VETC+HCC could benefit from
treatment with sorafenib in a subsequent study. Similarly, another study found that FGF 2 and
FGFR 3-4 (rather than VEGF-A or VEGFR 1-3) were high expression in VETC+ HCC, which raise the
possibility that lenvatinib is a potentially effective treatment modality. Recently, a
multicenter randomized controlled trial of postoperative adjuvant Sintilimab reported
encouraging positive results, suggesting the possibility of its application in VETC-positive
patients. Whether the combination of lenvatinib and Sintilimab can further improve the
prognosis is also worth exploring.
To address these clinical challenges, the investigators conducted a multicenter study
involving three surgical cohorts with postoperative active surveillance cohort(AC), adjuvant
Sintilimab cohort(AS), and adjuvant Sintilimab plus Lenvatinib cohort(ASL). The cases in the
AS cohort were mainly from a previous prospective cohort study initiated by the
investigator's center and a later cohort expansion (NCT05307926). Moreover, multi-omics
sequencing analysis aims to further explore the molecular biological characteristics between
VETC positive and negative HCC.