• Adverse events [ Time Frame: 6-8 weeks ]
  Safety evaluation was done continuously during ICIs treatment and up to 30 days after the last dose by using the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Complications related to ablation procedure were assessed peri-operation period and reported according to the standardized Society of Interventional Radiology grading system.
• Response [ Time Frame: 6-8 weeks ]
  Efficacy included objective response (includes complete and partial response), duration of response, and disease control (Includes complete and partial response, stable disease and atypical progression for at least 3 months).

• Time to tumor progression [ Time Frame: 3-4 months ]
  time from first dose of ICIs drug until the first typical progression of disease
• Progression-free survival [ Time Frame: 3-4 months ]
  time from first day of ICIs treatment to first typical disease progression, or death, which occurred earlier
• Overall survival [ Time Frame: 3-4 months ]
  time from first study treatment to death of any cause

Hepatocellular carcinoma (HCC) is ranked as the third leading cause of cancer death both worldwide and in the China. In the past decade, survivals of patients with advanced HCC or those who have progressed diseases following locoregional treatments can be increased with the multi-kinase inhibitor sorafenib, the first evidence identified drug for HCC. Recent clinical trials further verified some novel tyrosine kinase inhibitors such as regorafenib and cabozantinib, and two programmed cell death protein-1 (PD-1) immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab, as useful therapies in second line setting following sorafenib.

Advances in programmed cell death protein 1 (PD-1) blockade have shown an ORR of 15-17% and median survival time of 12.9-15.0 months among patients with advanced HCC. Of these, nivolumab and pembrolizumab have been accelerated approved as second-line treatment of advanced HCC. Notably, patients who have tumor responses maintain long-lasting disease control for 9.9-17months and still a large proportion of patients (81-83%) do not respond to mono PD-1 blockade, which emphasizing the need to explore strategies to increase the efficacy of immunotherapy.

An approach to expanding the benefit of ICIs may involve combinations with locoregional therapy like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), such treatments have been shown to boost tumor-specific T-cell response through release of TAAs from HCC cells. The intent-to-treat population of this study was a subset of patients receiving ongoing ICIs therapy for advanced HCC and is with stable disease or atypical responses in different lesions of the same individuals.

Inclusion Criteria:

Eligible patients had pathological diagnosis of HCC by either surgical resection tissue or core needle biopsy; and had advanced stage of disease that is refractory to or is with unacceptable toxicity of sorafenib. Other eligibility criteria included: Child-Pugh A or B7 classification; Eastern Cooperative Oncology Group-performance status score 0-2; adequate bone marrow (leukocyte count >3.0 ×109/L, hemoglobin >8.0 g/L, and platelet count >60 ×109/L), liver (alanine aminotransferase and aspartate aminotransferase <200 IU/mL), renal (creatinine <1.5 times the upper limit of the normal range) and coagulation (international normalized ratio <2.3) function.

Exclusion Criteria:

• Exclusion criteria included a history of treatment with immune checkpoint inhibitors, allergies to immunetherapeutics, systemic immunosuppressive therapy, and ongoing or active infection, or an active autoimmune disease.