Estimation and Prediction of Individual Benefit From Postoperative Adjuvant Transcatheter Arterial Chemoembolization For Patients With Hepatocellular Carcinoma (HCC)

Adjuvant transarterial chemoembolization (TACE) is widely adopted in China for resectable hepatocellular carcinoma (HCC), yet its efficacy remains inconsistent. We aimed to identify factors influencing individual patient benefit using causal machine learning. To this end, we retrospectively collected HCC patients with high risk factors for tumor recurrence from four centers of China, divided into the discovery cohort and the validation cohort . The primary endpoint was disease-free survival (DFS). The primary endpoint was overall survival (OS).Individual treatment effects (ITEs) were estimated within a causal machine learning framework. An ITE < 0 was considered recommendation for adjuvant TACE , while ITE ≥ 0 indicated active surveillance. The model would be validated in the validation cohort. The contribution of each variable to ITE was assessed using the Shapley Additive Explanations (SHAP). An online calculator would be developed for future use by public.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma (HCC); Machine Learning; Adjuvant Therapy; Treatment Effectiveness; Transarterial Chemoembolization

• Study Type: Observational
• Enrollment (Actual): 1005

Contacts and Locations

Study Locations

• China
  • Anhu
    • Hefei, Anhu, China, 23000
      • The First Affiliated hospital of USTC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HCC patients with high-risk factors of tumor relapse, who received adjuvant TACE or active postoperative survelliance as treatment.

Description

Inclusion Criteria:

• (1) pathologic diagnosis of HCC; (2) received potentially curative hepatectomy with negative cut margins confirmed by pathology; (3) high risk of recurrence, meeting any of the following criteria: largest tumor >5 cm, multiple lesions, poor histological differentiation (Edmondson-Steiner grade III or IV), presence of microvascular invasion or satellite nodules, (4) received adjuvant TACE or active surveillance as postoperative treatment; (5) at least one year of follow-up.

Exclusion Criteria:

• (1) history of other malignancies; (2) received preoperative anti-tumor treatment; (3) presence of vascular invasion or extrahepatic metastasis; (4) tumor recurred within 4 weeks postoperatively; (5) residual tumor was detected by digital subtraction angiography (DSA); (6) received other types of adjuvant therapy; (7) cases with missing data exceeding 10%.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Discovery cohort; The cohort is used for training of the causal machine learning model
Validation cohort; The cohort is used for validation of the causal machine learning model
Adjuvant Tace Group; Patients who received adjuvant TACE as postoperative treatment
Active Surveillance Group; Patients who received active surveillance as postoperative treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Disease-free survival (DFS) was defined as the time from the date of curative-intent HCC surgery to the first occurrence of local recurrence, distant metastasis, or death from any cause, whichever came first. Patients without any of these events were censored at the last follow-up.	From January 2018 to December 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall Survival (OS) was defined as the time from the date of curative-intent HCC surgery to the first occurrence of death from any cause. Patients who were still alive at the last follow-up were censored at the date of the last follow-up.	From January 2018 to December 2023

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; No.2 People's Hospital of Fuyang City; Sun Yat-Sen University Cancer Center
• Investigators: Principal Investigator: Lianxin Liu, Ph.D., The First Affiliated hospital of USTC

Publications and helpful links

General Publications

• Wang Z, Ren Z, Chen Y, Hu J, Yang G, Yu L, Yang X, Huang A, Zhang X, Zhou S, Sun H, Wang Y, Ge N, Xu X, Tang Z, Lau W, Fan J, Wang J, Zhou J. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin Cancer Res. 2018 May 1;24(9):2074-2081. doi: 10.1158/1078-0432.CCR-17-2899. Epub 2018 Feb 2.
• Wei W, Jian PE, Li SH, Guo ZX, Zhang YF, Ling YH, Lin XJ, Xu L, Shi M, Zheng L, Chen MS, Guo RP. Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond). 2018 Oct 10;38(1):61. doi: 10.1186/s40880-018-0331-y.
• Ma T, Bai X, Zhang Q, Chen W, Huang K, Qian T, Xu Y, Sun P, Chen Y, Xiao W, Sun K, Gao S, Liang T. Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial. Hepatology. 2025 Nov 1;82(5):1112-1121. doi: 10.1097/HEP.0000000000001233. Epub 2025 Jan 14.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: PA-TACE-ITE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For patients' privacy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No