Skip to main content
SpringerLink
Log in

Total tumor volume predicts survival following liver resection in patients with hepatocellular carcinoma

  • Original Article
  • Published:
Tumor Biology

An Erratum to this article was published on 04 March 2016

Abstract

Assessing the prognosis of patients with hepatocellular carcinoma (HCC) by the number and size of tumors is sometimes difficult. The main purpose of the study was to evaluate the prognostic value of total tumor volume (TTV), which combines the two factors, in patients with HCC who underwent liver resection. We retrospectively reviewed 521 HCC patients from January 2001 to December 2008 in our center. Patients were categorized using the tertiles of TTV. The prognostic value of TTV was assessed. With a median follow-up of 116 months, the 1-, 3-, and 5-year overall survival (OS) rates of the patients were 93.1 , 69.9, and 46.3 %, respectively. OS was significantly differed by TTV tertile groups, and higher TTV was associated with shorter OS (P < 0.001). Multivariate analysis revealed that TTV was an independent prognostic factor for OS. Larger TTV was significantly associated with higher alpha-fetoprotein level, presence of macrovascular invasion, multiple tumor lesions, larger tumor size, and advanced tumor stages (all P < 0.05). Within the first and second tertiles of TTV (TTV ≤ 73.5 cm3), no significant differences in OS were detected in patients within and beyond Milan criteria (P = 0.183). TTV-based Cancer of the Liver Italian Program (CLIP) score gained the lowest Akaike information criterion value, the highest χ 2 value of likelihood ratio test, and the highest C-index among the tested staging systems. Our results suggested that TTV is a good indicator of tumor burden in patients with HCC. Further studies are warranted to validate the prognostic value of TTV.

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
Fig. 4

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

LR:

Liver resection

TTV:

Total tumor volume

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

AFP:

Alpha-fetoprotein

TNM:

Tumor-node-metastasis

BCLC:

Barcelona Clinic Liver Cancer stage

CLIP:

Cancer of the Liver Italian Program

AIC:

Akaike information criterion

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA: a Cancer J Clin. 2015;65(1):5–29.

    Google Scholar 

  2. Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. Clin Gastroenterol Hepatol. 2015;13(12):2140–51.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379(9822):1245–55.

    Article  PubMed  Google Scholar 

  4. de Martel C, Maucort-Boulch D, Plummer M, Franceschi S. World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. Hepatology. 2015;62(4):1190–200.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Santi V, Buccione D, Di Micoli A, Fatti G, Frigerio M, Farinati F, et al. The changing scenario of hepatocellular carcinoma over the last two decades in Italy. J Hepatol. 2012;56(2):397–405.

    Article  PubMed  Google Scholar 

  6. Altekruse SF, McGlynn KA, Dickie LA, Kleiner DE. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992–2008. Hepatology. 2012;55(2):476–82.

    Article  PubMed  Google Scholar 

  7. Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59.

    CAS  PubMed  Google Scholar 

  8. Zhong JH, Ke Y, Gong WF, Xiang BD, Ma L, Ye XP, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg. 2014;260(2):329–40.

    Article  PubMed  Google Scholar 

  9. Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology. 2002;35(3):519–24.

    Article  PubMed  Google Scholar 

  10. Nathan H, Hyder O, Mayo SC, Hirose K, Wolfgang CL, Choti MA, et al. Surgical therapy for early hepatocellular carcinoma in the modern era: a 10-year SEER-Medicare analysis. Ann Surg. 2013;258(6):1022–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fonseca AL, Cha CH. Hepatocellular carcinoma: a comprehensive overview of surgical therapy. J Surg Oncol. 2014;110(6):712–9.

    Article  PubMed  Google Scholar 

  12. Mazzaferro V, Lencioni R, Majno P. Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation. Semin Liver Dis. 2014;34(4):415–26.

    Article  PubMed  Google Scholar 

  13. 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(11):693–9.

    Article  CAS  PubMed  Google Scholar 

  14. Yamamoto J, Kosuge T, Saiura A, Sakamoto Y, Shimada K, Sano T, et al. Effectiveness of hepatic resection for early-stage hepatocellular carcinoma in cirrhotic patients: subgroup analysis according to Milan criteria. Jpn J Clin Oncol. 2007;37(4):287–95.

    Article  PubMed  Google Scholar 

  15. Ng KK, Vauthey JN, Pawlik TM, Lauwers GY, Regimbeau JM, Belghiti J, et al. Is hepatic resection for large or multinodular hepatocellular carcinoma justified? Results from a multi-institutional database. Ann Surg Oncol. 2005;12(5):364–73.

    Article  PubMed  Google Scholar 

  16. Toso C, Meeberg G, Hernandez-Alejandro R, Dufour JF, Marotta P, Majno P, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62(1):158–65.

    Article  CAS  PubMed  Google Scholar 

  17. Toso C, Trotter J, Wei A, Bigam DL, Shah S, Lancaster J, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2008;14(8):1107–15.

    Article  PubMed  Google Scholar 

  18. Macaron C, Hanouneh IA, Lopez R, Aucejo F, Zein NN. Total tumor volume predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria. Transplant Proc. 2010;42(10):4585–92.

    Article  CAS  PubMed  Google Scholar 

  19. Lee YH, Hsia CY, Hsu CY, Huang YH, Lin HC, Huo TI. Total tumor volume is a better marker of tumor burden in hepatocellular carcinoma defined by the Milan criteria. World J Surg. 2013;37(6):1348–55.

    Article  PubMed  Google Scholar 

  20. Edge SB. American Joint Committee on Cancer. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  21. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28(3):751–5.

  22. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.

    Article  CAS  PubMed  Google Scholar 

  23. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56(4):918–28.

    Article  CAS  PubMed  Google Scholar 

  24. Hosmer DW, Hosmer T, Le Cessie S, Lemeshow S. A comparison of goodness-of-fit tests for the logistic regression model. Stat Med. 1997;16(9):965–80.

    Article  CAS  PubMed  Google Scholar 

  25. Newson RB. Comparing the predictive powers of survival models using Harrell’s C or Somers’ D. Stata J. 2010;10(3):339–58.

    Google Scholar 

  26. Forster MR. Key concepts in model selection: performance and generalizability. J Math Psychol. 2000;44(1):205–31.

    Article  CAS  PubMed  Google Scholar 

  27. Jung YK, Jung CH, Seo YS, Kim JH, Kim TH, Yoo YJ et al. BCLC stage B is a better designation for single large hepatocellular carcinoma than BCLC stage A. Journal of gastroenterology and hepatology. 2015.

  28. Nanashima A, Tobinaga S, Kunizaki M, Miuma S, Taura N, Takeshita H, et al. Strategy of treatment for hepatocellular carcinomas with vascular infiltration in patients undergoing hepatectomy. J Surg Oncol. 2010;101(7):557–63.

    Article  PubMed  Google Scholar 

  29. Bertino G, Neri S, Bruno CM, Ardiri AM, Calvagno GS, Malaguarnera M, et al. Diagnostic and prognostic value of alpha-fetoprotein, des-gamma-carboxy prothrombin and squamous cell carcinoma antigen immunoglobulin M complexes in hepatocellular carcinoma. Minerva Med. 2011;102(5):363–71.

    CAS  PubMed  Google Scholar 

  30. Lee YH, Hsu CY, Huang YH, Su CW, Lin HC, Hsia CY, et al. Alpha-fetoprotein-to-total tumor volume ratio predicts post-operative tumor recurrence in hepatocellular carcinoma. J Gastrointest Surg. 2013;17(4):730–8.

    Article  PubMed  Google Scholar 

  31. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 2000;31(4):840–5.

  32. Marrero JA, Kudo M, Bronowicki JP. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist. 2010;15 Suppl 4:23–33.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by the National High-Tech R&D (863) Program of China (2015AA020408), the National Natural Science Foundation of China (81201967), the Beijing Natural Science Foundation (7144238), and Beijing Nova Program (No. 2009A69).

Author information

Authors and Affiliations

  1. Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), No. 17, Panjiayuan Nanli, Beijing, 100021, People’s Republic of China

    Mu-xing Li, Hong Zhao, Xin-yu Bi, Zhi-yu Li, Zhen Huang, Jian-guo Zhou, Jian-jun Zhao, Ye-fan Zhang, Dong-bin Zhao & Jian-qiang Cai

  2. Department of Interventional Therapies, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), No. 17, Panjiayuan Nanli, Beijing, 100021, People’s Republic of China

    Yue Han

  3. Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), No. 17, Panjiayuan Nanli, Beijing, 100021, People’s Republic of China

    Wen-qiang Wei

Authors
  1. Mu-xing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin-yu Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-yu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhen Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yue Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jian-guo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-jun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ye-fan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wen-qiang Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dong-bin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jian-qiang Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian-qiang Cai.

Ethics declarations

Conflicts of interest

None

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s13277-016-4992-3.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Mx., Zhao, H., Bi, Xy. et al. Total tumor volume predicts survival following liver resection in patients with hepatocellular carcinoma. Tumor Biol. 37, 9301–9310 (2016). https://doi.org/10.1007/s13277-016-4794-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-4794-7

Keywords

Search

Navigation