Case Report: Antiangiogenic Therapy Plus Immune Checkpoint Inhibitors Combined With Intratumoral Cryoablation for Hepatocellular Carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with high incidence and poor prognosis. Common treatment methods include surgery, transcatheter arterial chemoembolization (TACE), ablation, and targeted therapy. In recent years, combination treatment with antiangiogenic therapy and immune checkpoint inhibitors has made great progress in the treatment of advanced HCC. Here, we report the case of a patient with HCC who achieved a durable benefit from anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation.Main BodyA 38-year-old male patient initially presented with severe abdominal pain that was identified as an HCC rupture and hemorrhage by computed tomography (CT). The patient underwent emergency surgery and postoperative pathology confirmed HCC. The patient received prophylactic TACE after surgery. Unfortunately, three months after surgery, the patient developed multiple liver metastases. Subsequently, he received systemic anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation. After treatment, the patient achieved extensive tumor necrosis and the disease was effectively controlled.ConclusionsAnti-angiogenic therapy and immune checkpoint inhibitors combined with cryoablation can induce a powerful and effective systemic anti-tumor immune response, which is worthy of further research.

Clinical application status and prospect of the combined anti-tumor strategy of ablation and immunotherapy

“…AQP inhibitors (mercuric chloride) combinate with cryoablation significantly reverses resistance and improve treatment effects ( 109 , 110 ), which supported AQP inhibitors in combination with cryoablation-immunotherapy in clinical practice. Combined cryoablation with Toripalimab (anti-PD-1) and Lenvatinib (anti-angiogenic agent) in a metastatic HCC patient also achieved CR at 7 months after treatment, and PFS as 24 months ( 111 ). Compared with cryoablation-chemotherapy and cryoablation-DC-CIK cell therapy, combinate treatment of cryoablation-immunotherapy-chemotherapy showed the longest median OS estimation in metastatic NSCLC (27 months, 95%CI, 26.6-37.0, P <0.001) ( 112 ).…”

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies

“…The data on cryoablation plus ICIs are limited. However, in a case report of a patient with metastatic HCC post-surgery, cryoablation with lenvatinib and toripalimab led to a complete response after 7 months post-treatment and a PFS of 24 months at the time of manuscript submission [272]. Another study found that cryoablation with DCs-cytokineinduced killer cell immunotherapy in metastatic HCC led to a significantly higher median OS than in the cryotherapy group alone (p < 0.05) [273].…”

Threatment Strategies for Recurrent Hepatocellular Carcinoma Patients: Ablation and its Combination Patterns

“…Thus, TKIs might enhance the antitumor effects and reduce drug resistance to ICIs 99 , 100 . Li et al reported that a patient with metastatic HCC who had disease recurrence following surgery and then received CRA followed by combined lenvatinib and toripalimab achieved a complete response after 7 months of treatment and a PFS of 24 months in the latest reported 101 .…”