Supplementary Material for: Conversion surgery after immune checkpoint inhibitor-based combination therapy for initially unresectable hepatocellular carcinoma: A retrospective cohort study

Introduction: Hepatocellular carcinoma (HCC) has a high incidence rate and is often asymptomatic in its early stages. Combination therapies using immune checkpoint inhibitors (ICIs) have demonstrated survival benefits and high objective response rates, offering hope for conversion surgery in patients with initially unresectable HCC. We aimed to investigate the oncological outcomes of conversion surgery compared to those with continuing systemic treatment alone in patients who responded well to ICIs-based therapy, as well as the surgical outcomes associated with conversion surgery.

Methods: We consecutively enrolled patients diagnosed with HCC between January 1, 2019 and February 1, 2024. These patients received treatment with ICIs combined with either anti-VEGF antibodies or tyrosine kinase inhibitors. Tumor response and resectability were assessed every 2 months. Patients who responded positively and met the criteria for conversion surgery were included.

Results: Among 613 patients with initially unresectable HCC, 128 achieved conversion and met the surgical resection criteria during combination therapy. Of these, 54 continued non-surgical comprehensive treatment, 74 underwent conversion surgery, and 57 continued their original treatment post-surgery. The median follow-up time was 24.1 and 42.5 months for the surgery and non-surgery groups, respectively. The median PFS was 29.4 months in the surgery group versus 11.2 months in the non-surgery group (P<0.0001, hazard ratio [HR]=0.39 [0.24–0.63]). The median OS was not reached in the surgery group, compared to 25.4 months in the non-surgery group (P<0.0001, HR=0.26 [0.14–0.46]). Multivariate Cox regression analysis indicated that conversion surgery was independently associated with improved OS and PFS (P<0.001), and continuing the original treatment post-surgery significantly influenced OS and recurrence -free survival.

Conclusion: Conversion surgery after meeting the surgical criteria during immunotherapy provides significant prognostic benefits for patients with initially unresectable HCC, demonstrating high safety and R0 resection rates. For those undergoing conversion surgery, promptly resuming the original treatment after surgery is necessary.