953P - Vessels that encapsulate tumor clusters (VETC): A promising prognostic predictor for patients with hepatocellular carcinoma treated with tyrosine kinase inhibitor and immunotherapy combinations

Background

Vascular encapsulated tumor clusters (VETC) represent a distinctive manifestation of hepatocellular carcinoma (HCC). VETC-positive cases exhibit a characteristic pattern wherein neoplastic cells are surrounded by a contiguous layer of endothelial cells, promoting vascular dissemination and metastasis. Treatment strategies for advanced HCC predominantly involve tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI). The resurgence of interest in HCC morphology, prompted by the increasing utilization of HCC biopsy in clinical studies, underscores the potential utility of morphological features as prognostic or predictive biomarkers.

Methods

The investigated cohort comprised 125 patients, each possessing obtainable tumor biopsy specimens and comprehensive clinical records, inclusive of longitudinal follow-up data. For each case, five consecutive tissue sections were subjected to staining with H/E, CD34, GS, CD3, and CD79. CD34 immunostaining was employed to discern the presence of VETC, utilizing a defined threshold of 5% positivity to delineate VETC-positive cases. Additionally, GS, CD3, and CD79 served as surrogate markers for the immune classification of HCC.

Results

Among clinical features, BCLC stage and alpha-fetoprotein (AFP) showed a significant impact on OS in multivariable analysis. Among morphological features, namely HCC histotype and grade, VETC+, high number of CD3/CD79 and diffuse and strong GS staining, were not correlated with prognosis. In particular, VETC+ cases had a median OS of 12 months as compared to 11 months for VETC- cases [P=0.91]. By contrast, VETC showed an important correlation with treatment’s benefit. Indeed, VETC+ patients had a significantly longer OS when treated with TKI and ICI combinations as compared to those treated with ICI or TKI alone [P=0.001]. This difference was not observed in the subgroup of patients with VETC- phenotype [P=0.51].

Conclusions

In advanced HCC, VETC+ cases have a significantly better response to tyrosine kinase inhibitor and immunotherapy combinations. This result candidates VETC+ as a powerful predictive biomarker in HCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.