Effect of the combination of systemic and locoregional therapy on tumor recurrence and survival after liver transplantation for hepatocellular carcinoma (HCC).

4135 Background: Liver Transplantation (LT) results in the best survival in select HCC patients. Patients that do not meet transplant criteria based on tumor burden may require bridging therapies to downstage their disease to become eligible for LT. There is limited data on safety and efficacy of combining systemic therapy with locoregional therapy (LRT) prior to LT. Methods: This study was a single-center retrospective outcome analysis of all patients diagnosed with HCC who underwent LT between June 2018 and March 2024 ( n = 104 ) with primary endpoints being 1-year post-LT survival and post-LT tumor recurrence. Explant pathology was also examined to assess tumor necrosis, viability, grade, and lymphovascular invasion. Patients were categorized into 2 groups: 1) LRT alone and 2) combination of LRT and systemic therapy. LRT included Transarterial chemoembolization, Radioembolization, Microwave Ablation, and Stereotactic Beam Radiation Therapy. Systemic therapies included Nivolumab + Ipilimumab, Atezolizumab + Bevacizumab, Sorafenib, Lenvatinib, Ramuricumab, and Cabozantinib. Pearson correlation analysis was used. Results: 89 patients received LRT alone and 15 patients received combination therapy. The median maximum tumor diameter in the LRT group was 2.4 cm and that of the combination group was 2.5 cm ( p = 0.136 ). Patients in the combination therapy group also had a 3.5-fold increase in the average number of tumors, suggesting higher tumor burden. Average time to post-LT tumor recurrence was similar in combination therapy vs. LRT group (496.8 days vs. 546 days; p = 0.41 ). Patients receiving combination therapy had a trend towards better survival however this did not achieve statistical significance ( r = 0.13, p = 0.175 ). A statistically significant negative correlation existed between not meeting Milan criteria at the time of transplant evaluation and post-transplant tumor recurrence (i.e., rate of post-transplant tumor recurrence increased if the Milan criteria were not satisfied; r = -0.31, p < 0.001 ). Conclusions: Our results show that combination therapy using systemic options in addition to LRT is an effective downstaging strategy for high-risk HCC patients and may improve post-transplant survival and reduce post-LT tumor recurrence. This preliminary data suggests that combination therapy may have a favorable impact on the time to post-LT tumor recurrence in patients with higher risk tumors. This further attests the strong need for sustainable downstaging pre transplantation. Using the synergistic effect of these modalities may help expand the pool of candidates who can undergo LT, which remains the most effective long term therapy for patients with HCC. We did not find any evidence of increased rejection or opportunistic infections post LT in the combination therapy cohort.