A Single-center Study of the Synergistic Effect of Portal Venous Supply Control and Immunotherapy in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common solid malignant tumors and the main cause of cancer-related deaths worldwide. The main treatment method for patients with unresectable or advanced HCC (such as patients with vascular invasion, distant metastasis, or tumor-related symptoms) is systemic therapy such as immunotherapy combined with targeted drugs. The median OS of patients treated with first-line bevacizumab (T)+atilizumab (A) was 19.2 months, and the ORR was 30%; The median OS was 22 months and the ORR was 36% when the Lenvatinib+Pembrolizumab (K-drug) regimen was used in the second-line treatment of patients with unresectable HCC. At present, the combination of domestic PD-L1 monoclonal antibody, Camrelizumab, and VEGFR-2 inhibitor, Apatinib, shows great potential in the treatment of Chinese patients with unresectable HCC. Phase II data shows that the ORR, DCR, mPFS, and mOS for first-line treatment are 34%, 77%, 5.7 months, and 20.3 months respectively.

However, the benefits for patients are still very limited, and the clinical treatment of non-resectable HCC is facing serious challenges. Therefore, it is necessary to take a reasonable multidisciplinary comprehensive treatment strategy, to establish a new effective treatment plan and further improve the prognosis and quality of life of patients.

The anti-vascular treatment of HCC is the basis of immunotherapy and an important trigger and intensifier. The reason and mechanism are that hepatocellular carcinoma can be secondary to liver injury caused by various reasons, such as chronic alcohol consumption, chronic hepatitis B and C infection, non-alcoholic fatty liver, etc., but all of them are manifested by increased blood vessels and significant vascular abnormalities, which suggests that blood supply plays an important role in the occurrence and development of HCC. A large number of targeted anti-vascular drugs have been used in the treatment of hepatocellular carcinoma. Angiogenesis inhibitors can specifically inhibit VEGF-mediated dendritic cell maturation disorder, promote antigen presentation and T cell immune response to tumor antigen; At the same time, it antagonizes angiogenesis, blocks tumor blood supply, normalizes tumor blood vessels, and increases T cell infiltration in tumor cells.

The hepatic artery is the main blood supply source of the tumor, so angiogenesis inhibitors often combine with TACE to directly and effectively block the blood supply of the tumor, which can not only effectively inhibit angiogenesis around the tumor, but also delay the progress of tumor and thus improve the effect of tumor treatment. It is noteworthy that portal vein blood flow also plays an important role in the occurrence and development of HCC.

Angiogenesis inhibitors can directly or indirectly affect the portal vein blood flow and improve the prognosis. It has been reported in the literature that angiogenic inhibitors such as sorafenib and lenvatinib can significantly reduce portal vein pressure and effectively prolong the survival period of advanced HCC.