Liver Transplantation After Radiotherapy-Antiangiogenesis-Immune Checkpoint Blockade Combination Therapy in Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Propensity Score Matching Analysis

Ying Zhao,1,* Jiyong Song,2,* Keren Li,2,* Tao Li,1,* Wei Li,3 Yanmei Yang,1 Xuan Tong,2 Ying Xiao,4 Guangxun Xu,2 Qian Lu,2 Guangxin Li,1 Gong Li,1 Jiahong Dong2 1Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People’s Republic of China; 2Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People’s Republic of China; 3Clinical Trial Office, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People’s Republic of China; 4Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong Li, Email [email protected] Guangxin Li, Email [email protected]: After downstaging, radiotherapy-antiangiogenesis-immune checkpoint blockade (RACIB) combination therapy has shown significant clinical efficacy in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT), permitting liver transplantation (LT). This study evaluated LT patients’ survival outcomes and prognostic factors after RACIB treatment.Patients and Methods: This retrospective analysis comprised 28 HCC with major PVTT (Vp3/Vp4, portal invasion at the first portal branch or main portal branch according to Japanese Vp classification) patients who were downstaged with RACIB combination therapy between January 2018 and December 2022. 13 patients who achieved successful downstaging underwent LT (RACIB+LT group), while 15 patients who achieved downstaging but did not undergo LT (due to patient choice, lack of donor, or other clinical reasons) formed the non-LT control group (RACIB-only group). Kaplan–Meier analysis and the Log rank test were used for survival analysis. For comparative analysis, one-to-one paired cohorts were derived using propensity-score matching (PSM) analysis.Results: Over a median follow-up period of 32.1 months (range: 4.1– 46.0 months), the median overall survival (OS) and disease-free survival (DFS) were 31.1 and 10.1 months in the LT following RACIB group, and 14.5 months and 7.6 months in the RACIB group, respectively. The LT following RACIB group exhibited significantly better 3-year OS (42% vs 0, p=0.041) and 3-year progression-free survival (15.4% vs 0, p=0.047) than those who only underwent RACIB. In the PSM analysis, the 2-year OS was also superior in the LT following RACIB group (45.7% vs 0, p=0.042). Kaplan–Meier analysis showed that long interval from radiotherapy (RT) to LT, alpha fetoprotein (AFP) levels dropped to normal, AFP was reduced by half and patients with major pathologic response had superior OS (p=0.014, 0.005, 0.019, and 0.023) and DFS (p=0.025, 0.013, 0.011, and 0.014) compared to patients without any of the parameters. In DFS multivariate analysis, the interval from RT to LT and AFP normalization before LT were independent prognostic factors. The RACIB regimen was well tolerated, with no grade ≥ 3 treatment-related adverse events observed.Conclusion: Selected HCC patients with major PVTT can be considered viable candidates for LT after downstaging using RACIB combination therapy, with identified prognostic parameters aiding decision-making.Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, liver transplantation, major pathological response, radiotherapy-antiangiogenesis-immune checkpoint blockade combination therapy