The Value of no Evidence of Disease (NED) in Intermediate-Stage Hepatocellular Carcinoma After TACE: A Real-World Study
Lujun Shen
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYiquan Jiang
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYueqian Wu
Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorChen Li
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorQi Zeng
Department of Traditional Chinese Medicine Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
Search for more papers by this authorLetao Lin
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYujia Wang
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorShuanggang Chen
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorFei Cao
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorGulijiayina Nuerhashi
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorSen Zhang
Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
Search for more papers by this authorZhongguo Zhou
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
Search for more papers by this authorCorresponding Author
Chao An
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorCorresponding Author
Zhicheng Du
Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorCorresponding Author
Weijun Fan
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorLujun Shen
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYiquan Jiang
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYueqian Wu
Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorChen Li
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorQi Zeng
Department of Traditional Chinese Medicine Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China
Search for more papers by this authorLetao Lin
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorYujia Wang
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorShuanggang Chen
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorFei Cao
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorGulijiayina Nuerhashi
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Search for more papers by this authorSen Zhang
Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
Search for more papers by this authorZhongguo Zhou
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
Search for more papers by this authorCorresponding Author
Chao An
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorCorresponding Author
Zhicheng Du
Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorCorresponding Author
Weijun Fan
Department of Minimally Invasive Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China
Correspondence:
Chao An ([email protected])
Zhicheng Du ([email protected])
Weijun Fan ([email protected])
Search for more papers by this authorHandling Editor: Alejandro Forner
Funding: This work was supported by Guangzhou Municipal Science and Technology Project (202201011375).
Lujun Shen, Yiquan Jiang, Yueqian Wu and Chen Li contributed equally to this work.
ABSTRACT
Background and Aims
One-third of patients with intermediate-stage hepatocellular carcinoma (HCC) can achieve imaging-based no evidence of disease (NED) during treatment after transarterial chemoembolization (TACE) and sequential therapies; however, its temporal dynamics, contributing factors and prognostic value remain unknown.
Methods
The longitudinal data of 1665 intermediate-stage HCC patients from Sun Yat-sen University Cancer Center were included as a derivation cohort; 414 patients from three external medical centers served as the validation cohort. Image-Only NED is defined as no evidence of disease based on imaging exams while having a serum level of alpha-fetoprotein (AFP) above the upper limit; Image-Bio NED pertains to an additional achievement of a normal level of AFP. A semi-Markov multistate model was adopted to identify the transitions between intermediate states, which included NED unreached, Image-Only NED, Image-Bio NED, recurrence after NED and death. A time-dependent Cox proportional hazards model for overall survival (OS) was utilised to evaluate the dynamic prognostic value of NED states.
Results
The percentage of patients who reached Image NED and Image-Bio NED was 35.2% and 24.7% in the derivation cohort, and 37.4% and 31.4% in the validation cohort. The proportion of Image-Only NED and Image-Bio NED peaked by the end of the second year since initial treatment and declined gradually. Patients with Image-Only NED had a higher risk of recurrence compared to the Image-Bio NED subgroup (p < 0.05). With the subgroup of NED unreached as reference, the multivariate time-dependent Cox model showed Image-Only NED (HR 0.44; 95% CI 0.33–0.59) and Image-Bio NED (HR 0.26; 0.20–0.33) were significant intermediate states that predict distinct OS for patients with intermediate-stage HCC, which was further confirmed in the multi-centre validation cohort.
Conclusions
Our study highlights the clinical course of NED states and demonstrates its dynamic prognostic significance in patients with intermediate-stage HCC after TACE. The Image-Bio NED is recommended to serve as an important endpoint during the dynamic management of intermediate-stage HCC.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
Data are available from the corresponding author upon reasonable request. The authenticity of this data has been validated by uploading the critical raw data onto the Research Data Deposit public platform (www.researchdata.org.cn).
Supporting Information
| Filename | Description |
|---|---|
| liv70101-sup-0001-FigureS1.tifTIFF image, 7.9 MB |
Figure S1. The design of the transitions between different NED states. |
| liv70101-sup-0002-FigureS2.tifTIFF image, 3.1 MB |
Figure S2. The Kaplan–Meier curves on OS of different NED intermediate states based on data of different time slices. To build the curves, the longitudinal data were transformed into data of time slices, with an interval of 3 months. For patients with multiple measurements of NED state in specific time slice, the newest state was selected to be associated with the time slice. The KM plots showed OS divided by the NED states in the SYSUCC cohort and multicentric external cohort, respectively, at time slice No. 2 (A, B), No. 4 (C, D) and No. 6 (E, F). |
| liv70101-sup-0003-TableS1.docxWord 2007 document , 12.2 KB |
Table S1. The number of patients receiving surgical resection or ablative therapy with curative intent at different time periods during dynamic management. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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