Skip to main content
SpringerLink
Log in

Surgical Resection is Better than Transarterial Chemoembolization for Patients with Hepatocellular Carcinoma Beyond the Milan Criteria: A Prognostic Nomogram Study

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The clinical outcomes in hepatocellular carcinoma (HCC) patients receiving surgical resection (SR) or transarterial chemoembolization (TACE) are diverse. This study aimed to develop a nomogram to predict individualized survival risk in patients with HCC beyond the Milan criteria undergoing aggressive treatments (SR and TACE).

Methods

A total of 1009 patients were enrolled in the study and randomly grouped into derivation (n = 505) and validation sets (n = 504). The multivariate Cox proportional hazards model was used to select significant prognostic predictors from the derivation set to generate the nomogram. The performance of the nomogram was evaluated by discrimination (concordance index) and calibration tests.

Results

Serum albumin <3.8 g/dL, α-fetoprotein ≥400 ng/mL, TACE, vascular invasion, multiple tumors, and tumor volume ≥200 cm3 were associated with poor survival in the multivariate Cox model (all p < 0.05). A nomogram with a scale of 0–47 was developed with these six variables, and the predicted survival rates at 1 and 3 years were calculated. The derivation set with bootstrapping (B = 100) had a good concordance index of 0.694 [95 % confidence interval (CI) 0.68–0.708]. Discrimination test in the validation set provided a concordance index of 0.71 (95 % CI 0.697–0.722), and the calibration plots well-matched the 45-degree line for 1- and 3-year survival prediction. The respective survival for patients undergoing SR or TACE could be predicted based on the nomogram across different risk scores.

Conclusions

This easy-to-use nomogram may accurately predict survival at 1 and 3 years for individual HCC patients beyond the Milan criteria, and provide quantitative survival advantage of SR over TACE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.

    Article  PubMed  Google Scholar 

  2. Weinmann A, Koch S, Niederle IM, Schulze-Bergkamen H, König J, Hoppe-Lotichius M et al. Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1066 cases of a German HCC Registry. J Clin Gastroenterol. 2014;48:279–89

    Article  PubMed  Google Scholar 

  3. Lopez PM, Villanueva A, Llovet JM. Systemic review: evidence-based management of hepatocellular carcinoma—an updated analysis of randomized controlled trials. Aliment Pharmacol Ther. 2006;23:1535–47.

    Article  CAS  PubMed  Google Scholar 

  4. Cabrera R, Nelson DR. Review article: the management of hepatocellular carcinoma. Aliment Pharmacol Ther. 2010;31:461–76.

    Article  CAS  PubMed  Google Scholar 

  5. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020–2.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Liu PH, Lee YH, Hsia CY, Hsu CY, Huang YH, Chiou YY et al. Surgical resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis. Ann Surg Oncol. 2014;21:1825–33

    Article  PubMed  Google Scholar 

  7. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693–9

    Article  CAS  PubMed  Google Scholar 

  8. Shi J, Lai EC, Li N, Guo WX, Xue J, Lau WY et al. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol. 2010;17:2073–80.

    Article  PubMed  Google Scholar 

  9. Truty MJ, Vauthey JN. Surgical resection of high-risk hepatocellular carcinoma: patient selection, preoperative considerations, and operative technique. Ann Surg Oncol. 2010;17:1219–25.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Hsu CY, Hsia CY, Huang YH, Su CW, Lin HC, Pai JT et al. Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria: a propensity score analysis. Ann Surg Oncol. 2012;19:842–9

    Article  PubMed  Google Scholar 

  11. Shim JH, Jun MJ, Han S, Lee YJ, Lee SG, Kim KM, et al. Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma. Ann Surg. 2015;261:939–46

    Article  PubMed  Google Scholar 

  12. Massarweh NN, Dickson PV, Anaya DA. Soft tissue sarcomas: staging principles and prognostic nomograms. J Surg Oncol. 2015;111:532–9.

    Article  PubMed  Google Scholar 

  13. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–30

    Article  CAS  PubMed  Google Scholar 

  14. Lee YH, Hsu CY, Hsia CY, Huang YH, Su CW, Chiou YY et al. Alcoholism worsens the survival of patients with hepatitis B virus and C virus-related hepatocellular carcinoma. Hepatol Int. 2013;7:645–54

    Article  PubMed  Google Scholar 

  15. Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, et al. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol. 2010;53:108–17.

    Article  PubMed  Google Scholar 

  16. Lee YH, Hsu CY, Huang YH, Hsia CY, Chiou YY, Su CW et al. Vascular invasion in hepatocellular carcinoma: prevalence, determinants and prognostic impact. J Clin Gastroenterol. 2014;48:734–41.

    Article  CAS  PubMed  Google Scholar 

  17. Hsu CY, Lee YH, Liu PH, Hsia CY, Huang YH, Lin HC, et al. Using serum α-fetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff? PLoS One. 2015;10:e0118825.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15:361–87.

    Article  PubMed  Google Scholar 

  19. Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med. 2004;23:2109–23.

    Article  PubMed  Google Scholar 

  20. Wang JH, Changchien CS, Hu TH, Lee CM, Kee KM, Lin CY, et al. The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma: survival analysis of 3892 patients. Eur J Cancer. 2008;44:1000–6.

    Article  PubMed  Google Scholar 

  21. Yamashita Y, Taketomi A, Shirabe K, Aishima S, Tsuijita E, Morita K et al. Outcomes of hepatic resection for huge hepatocellular carcinoma (≥10 cm in diameter). J Surg Oncol. 2011;104:292–8.

    Article  PubMed  Google Scholar 

  22. Liu PH, Lee YH, Hsu CY, Hsia CY, Huang YH, Chiou YY, et al. Surgical resection is better than transarterial chemoembolization for hepatocellular carcinoma beyond Milan criteria independent of performance status. J Gastrointest Surg. 2014;18:1623–31

    Article  PubMed  Google Scholar 

  23. Iasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008;26:1364–70.

    Article  PubMed  Google Scholar 

  24. Hsu CY, Lee YH, Hsia CY, Huang YH, Su CW, Lin HC, et al. Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system. Hepatology. 2013;57:112–9.

    Article  PubMed  Google Scholar 

  25. Hsu CY, Lee YH, Hsia CY, Huang YH, Su CW, Lin HC, et al. Performance status enhances the selection of treatment for patients with hepatocellular carcinoma within the milan criteria. Ann Surg Oncol. 2013;20:2035–42

    Article  PubMed  Google Scholar 

  26. Mazzaferro V, Lencioni R, Majno P. Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation. Semin Liver Dis. 2014;34:415–26.

    Article  PubMed  Google Scholar 

  27. Huo TI, Huang YH, Wu JC. Percutaneous ablation therapy for hepatocellular carcinoma: current practice and look into future. J Chin Med Assoc. 2005;68:155–9.

    Article  PubMed  Google Scholar 

  28. Colombo M, Sangiovanni A. Treatment of hepatocellular carcinoma: beyond international guidelines. Liver Int. 2015;35(Suppl 1):129–38.

    Article  CAS  PubMed  Google Scholar 

  29. Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York: Springer; 2001.

    Book  Google Scholar 

Download references

Acknowledgments

This study was supported by Grants from the Center of Excellence for Cancer Research at Taipei Veterans General Hospital, Taiwan (MOHW104-TDU-B-211-124-001), Taipei Veterans General Hospital, Taipei, Taiwan (V104C-008), and the Ministry of Education, Aiming for the Top University Plan, Taiwan (103AC-P618).

Author Contributions

Teh-Ia Huo is the overall guarantor of the article. Chia-Yang Hsu and Teh-Ia Huo performed the research; Yun-Hsuan Lee, Po-Hong Liu, Cheng-Yuan Hsia, Rheun-Chuan Lee, and Teddy S. Nagaria collected and analyzed the data; Chia-Yang Hsu and Teh-Ia Huo designed the research study and wrote the paper; Han-Chieh Lin contributed to the design of the study; and all authors approved the final version of the manuscript.

Conflict of interest

Chia-Yang Hsu, Po-Hong Liu, Cheng-Yuan Hsia, Yun-Hsuan Lee, Teddy S. Nagaria, Rheun-Chuan Lee, Han-Chieh Lin, and Teh-Ia Huo have indicated there are no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chia-Yang Hsu MD, MPH, Po-Hong Liu MD, Yun-Hsuan Lee MD, Han-Chieh Lin MD & Teh-Ia Huo MD

  2. Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Cheng-Yuan Hsia MD

  3. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

    Rheun-Chuan Lee MD

  4. Department of Internal Medicine, University of Nevada School of Medicine, Reno, NV, USA

    Chia-Yang Hsu MD, MPH

  5. Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Chia-Yang Hsu MD, MPH, Po-Hong Liu MD, Cheng-Yuan Hsia MD, Yun-Hsuan Lee MD, Rheun-Chuan Lee MD, Han-Chieh Lin MD & Teh-Ia Huo MD

  6. Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Teh-Ia Huo MD

  7. Department of Pathology, University of Toronto, Toronto, ON, Canada

    Teddy S. Nagaria MD, PhD

Authors
  1. Chia-Yang Hsu MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Po-Hong Liu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng-Yuan Hsia MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun-Hsuan Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teddy S. Nagaria MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rheun-Chuan Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Han-Chieh Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Teh-Ia Huo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teh-Ia Huo MD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2015_4929_MOESM1_ESM.tif

Supplementary Fig. 1 The predicted survival at 1 and 3 years by using the nomogram of HCC patients with tumor(s) beyond the Milan criteria undergoing SR (panel A) or TACE (panel B) (TIFF 356 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hsu, CY., Liu, PH., Hsia, CY. et al. Surgical Resection is Better than Transarterial Chemoembolization for Patients with Hepatocellular Carcinoma Beyond the Milan Criteria: A Prognostic Nomogram Study. Ann Surg Oncol 23, 994–1002 (2016). https://doi.org/10.1245/s10434-015-4929-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-015-4929-x

Keywords

Search

Navigation