Wenzhe Fan,1,* Xinlin Zheng,1,* Weihong Zhang,1,* Bowen Zhu,2 Yanqin Wu,1 Miao Xue,1 Rong Tang,3 Zhen Huang,4 Liangliang Qiao,5 Mingjian Lu,6 Jian Wu,7 Yiyang Tang,1 Jinghua Chen,8 Shugui Huang,9 Mingjun Bai,10 Jiaping Li1 

1Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Hepatopancreatobiliary Surgery, Hainan General Hospital, Haikou, People’s Republic of China; 4Department of Interventional Angiology, Huizhou First People’s Hospital, Huizhou, People’s Republic of China; 5Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People’s Republic of China; 7Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 8Cancer Center, Guangzhou Twelfth People’s Hospital, Guangzhou, People’s Republic of China; 9Department of General Surgery I, The First Affiliated Hospital of Guangzhou Pharmaceutical University, Guangzhou, People’s Republic of China; 10Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mingjun Bai, Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China, Tel +86-15918658559, Email baimingj@mail.sysu.edu.cn Jiaping Li, Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-13352890908, Email lijiap@mail.sysu.edu.cn

Purpose: Central bile duct invasion (BDI) by hepatocellular carcinoma (HCC) is rare and associated with poor prognosis, lacking treatment guidelines. While transarterial chemoembolization (TACE) is often used for unresectable cases, determining optimal candidates post-biliary drainage is controversial. We aim to develop a prognostic prediction model for unresectable HCC (uHCC) patients with central BDI receiving sequential TACE after successful biliary drainage.
Patients and Methods: We retrospectively analyzed 267 uHCC patients with central BDI receiving successful biliary drainage and sequential TACE from seven tertiary centers (2015– 2021), divided into training (n=187) and validation (n=80) sets. Using Cox proportional-hazards regression model, we identified key prognostic indicators for overall survival (OS) and constructed a prediction model.
Results: Pre-TACE total bilirubin (TBil) values, extrahepatic spread (EHS), multiple intrahepatic tumors (MIT), and portal vein tumor thrombus (PVTT) were identified as the significant clinical indicators for OS. These four parameters were included in a novel prediction model, named TEMP score, which could successfully categorize patients in the training set into three distinct risk grades with median OS of 26.9, 9.4, and 5.8 months, respectively. The TEMP score predicted the time-dependent areas under the receiver operating characteristic curves for OS at 6 months, 1 year, and 2 years of 0.813/0.907, 0.833/0.782, and 0.838/0.811 in the training and validation sets, with corresponding C-indices of 0.812/0.929, 0.829/0.761, and 0.818/0.791, respectively, outperforming other currently available models in both cohorts. The calibration curve of the model for predicting OS presented good consistency between observations and predictions in both the training set and validation set.
Conclusion: The TEMP score effectively stratifies the prognosis of uHCC patients with central BDI who have undergone successful bile drainage and sequential TACE, helping to identify those who may benefit from TACE treatment.

Keywords: bile duct invasion, hepatocellular carcinoma, transarterial chemoembolization, prognosis, risk stratification