The Application of Locoregional Therapy Combined With Systemic Therapy in the Perioperative Period of Huge Hepatocellular Carcinoma: A Retrospective Cohort Study

All procedures were performed by senior hepato-pancreato-biliary surgeons who completed over 100 hepatectomy procedures annually. Intraoperative ultrasound was routinely performed to identify any potential tumor nodules that were not detected before surgery and to help rule out parenchymal transection plane. The resection margin should extend 1 cm beyond the tumor edge whenever possible. Pringle's maneuver and the low central venous pressure technique were performed routinely.For difficult hepatectomy, the anterior approach (parenchymal transection without prior mobilization of the liver) was applied and the hepatic pedicle and the inferior vena cava below the liver were clamped simultaneously for better hepatic vascular inflow and outflow control. Liver parenchymal transection was performed by an ultrasonic scalpel. After surgery, all patients were followed up according to the visit schedules and contents recommended by the Chinese guidelines for HCC.

After surgery, patients who agreed to receive postoperative adjuvant therapy began to undergo immunotherapy when recovered well from the surgery and alanine aminotransferase and aspartate aminotransferase were both less than 80 U/L and total bilirubin was less than 2 mg/dL. Immune checkpoint inhibitors (ICIs) included pembrolizumab, atezolizumab, tislelizumab, sintilimab, camrelizumab, and toripalimab. The specific agents of ICIs were determined by the patients' wishes and consultation with their attending physicians. ICIs were injection once every 3 weeks for 12 months and would be terminated when disease progressed or intolerable toxicity occurred. Meanwhile, some patients underwent adjuvant transarterial chemoembolization (TACE) and/or target therapy.

Patients were treated preoperatively with a combination of immune checkpoint inhibitors (ICIs), targeted drugs, and locoregional interventions, such as transarterial chemoembolization (TACE) and/or and/or hepatic artery infusion chemotherapy (HAIC).ICIs included pembrolizumab, atezolizumab, tislelizumab, sintilimab, camrelizumab, toripalimab, and durvalumab. Targeted drugs included lenvatinib, bevacizumab, donafenib, sorafenib, regorafenib, and apatinib. The choice of different locoregional therapies and systemic therapy agents for HCC was made by weighing the patient's wishes, cost considerations, and multidisciplinary team (MDT) discussions. ICIs and targeted drugs were used until the disease progressed or an intolerable adverse event occurred.

Patients who received the neoadjuvant conversion therapy but eventually not underwent surgery