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Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study

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Abstract

Background

Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection.

Methods

Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves.

Results

Independent factors associated with death within 6 months of surgery included age, Child–Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542–0.748).

Conclusions

An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

PVTT:

Portal vein tumor thrombus

HVTT:

Hepatic vein tumor thrombus

PVE:

Portal vein embolization

ALPPS:

Associating liver partition and portal vein ligation for staged hepatectomy

TACE:

Transcatheter arterial chemoembolization

BSC:

Best supportive care

RCT:

Randomized controlled trial

ECOG:

Eastern Cooperative Oncology Group

ASA:

American society of anesthesiologists

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

INR:

International normalized ratio

TB:

Total bilirubin

ALT:

Alanine aminotransferase

AST:

Aspartate transaminase

AFP:

Alpha-fetoprotein

CT:

Computerized tomography

MRI:

Magnetic resonance imaging

ROC:

Receiver operating characteristic

TNM:

Tumor-node-metastasis

CLIP:

Cancer of the liver Italian program

BCLC:

Barcelona clinic liver cancer

DCA:

Decision curve analysis

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81672699 and 81972726). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China

    Lei Liang, Yong-Kang Diao, Hang-Dong Jia, Cheng-Wu Zhang, Dong-Sheng Huang & Tian Yang

  2. Department of Clinical Medicine, Second Military Medical University (Navy Medical University), Shanghai, China

    Bing Quan & Wen-Tao Yan

  3. Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China

    Han Wu, Hao Xing, Chao Li, Ming-Da Wang, Wan Yee Lau, Feng Shen & Tian Yang

  4. Hepatobiliary Cancer Institute, Hangzhou Medical College, Hangzhou, Zhejiang, China

    Lei Liang, Yong-Kang Diao, Hang-Dong Jia, Dong-Sheng Huang & Tian Yang

  5. Department of Hepatobiliary Surgery, Fuyang People’s Hospital, Anhui, China

    Jie Li

  6. Department of General Surgery, Ziyang First People’s Hospital, Sichuan, China

    Ting-Hao Chen

  7. The second Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Guangdong, China

    Yao-Ming Zhang

  8. Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Yunnan, China

    Ya-Hao Zhou

  9. Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

    Wan-Guang Zhang

  10. Department of General Surgery, Liuyang People’s Hospital, Hunan, China

    Hong Wang

  11. Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Bologna, Italy

    Matteo Serenari & Matteo Cescon

  12. Liver Cancer Program, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Myron Schwartz

  13. Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China

    Yong-Yi Zeng

  14. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China

    Ying-Jian Liang

  15. Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China

    Wan-Yuan Chen

  16. Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

    Wan Yee Lau

  17. Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA

    Timothy M. Pawlik

Authors
  1. Lei Liang
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  2. Bing Quan
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  3. Han Wu
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  4. Yong-Kang Diao
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  5. Jie Li
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  7. Yao-Ming Zhang
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  10. Hong Wang
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  14. Yong-Yi Zeng
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  17. Hao Xing
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  18. Chao Li
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  19. Ming-Da Wang
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  20. Wen-Tao Yan
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  21. Wan-Yuan Chen
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  22. Wan Yee Lau
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  27. Tian Yang
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Contributions

Drs L. Liang, Quan, Wu, Diao and Li contributed equally to this work. Drs Huang, Shen and Yang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: L. Liang, Quan, Lau, Huang, Shen, Yang. Administrative support: Shen, Zhang, Huang, Yang. Provision of study materials or patients: Lau, Pawlik, C.W. Zhang, Huang, Shen, Yang. Collection and assembly of data: L. Liang, Wu, Diao, Jia, Li, Chen, Zhang, Zhou, Zhang, Wang, Serenari, Cescon, Schwartz, Zeng, Liang, Xing, Li, Wang, Chen. Data analysis and interpretation: L. Liang, Quan, Wu, Diao, Jia, Xing, Yang. Manuscript writing: All authors. Final approval of manuscript: All authors. Obtained funding: Yang.

Corresponding authors

Correspondence to Dong-Sheng Huang or Tian Yang.

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Conflict of interest

None of the authors report any conflicts of interest.

Ethical approval

Informed consent was obtained from all patients before Flow chart of patient inclusion and the study was approved by the Institutional Review Board or Clinical Analyses at each of these hospitals. The study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies in all participating hospitals.

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Liang, L., Quan, B., Wu, H. et al. Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study. Hepatol Int 15, 459–471 (2021). https://doi.org/10.1007/s12072-021-10140-7

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  • DOI: https://doi.org/10.1007/s12072-021-10140-7

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