Skip to main content

Advertisement

SpringerLink
Log in

Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Background

For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients.

Methods

Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038).

Results

The median duration of sorafenib administration was 56.5 days (range 5–945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection.

Conclusions

A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

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

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

MST:

Median survival time

RECIST:

Response evaluation criteria in solid tumors

PS:

Performance status

AFP:

Alpha-fetoprotein

AFP-L3:

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein protein

DCP:

Des-gamma-carboxyl prothrombin

TACE:

Transarterial chemoembolization

RFA:

Radiofrequency ablation

NLCT:

New liver cancer therapies

PVTT:

Portal vein tumor thrombosis

References

  1. Llovet JM, Ricci S, Mazzaferro V, SHARP Investigators Study Group, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  2. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia–Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.

    Article  CAS  PubMed  Google Scholar 

  3. Nakano M, Tanaka M, Kuromatsu R, et al. Efficacy, safety, and survival factors for sorafenib treatment in Japanese patients with advanced hepatocellular carcinoma. Oncology. 2013;84:108–14.

    Article  CAS  PubMed  Google Scholar 

  4. Kaneko S, Furuse J, Kudo M, et al. Guideline on the use if new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update. Hepatol Res. 2012;42:523–42.

    Article  CAS  PubMed  Google Scholar 

  5. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology: hepatobiliary cancers. Version Fort Washington, PA: NCCN; 2014.

  6. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.

    Article  Google Scholar 

  7. Kudo M, Ueshima K. Positioning of a molecular-targeted agent, sorafenib, in the treatment algorithm for hepatocellular carcinoma and implication of many complete remission cases in Japan. Oncology. 2010;78(Suppl 1):154–66.

    Article  CAS  PubMed  Google Scholar 

  8. Kudo M, Matsui O, Izumi N, Liver Cancer Study Group of Japan, et al. Surveillance and diagnostic algorithm for hepatocellular carcinoma proposed by the Liver Cancer Study Group of Japan: 2014 update. Oncology. 2014;87(Suppl 1):7–21.

    Article  PubMed  Google Scholar 

  9. Tanaka K, Shimada M, Kudo M. Characteristics of long-term survivors following sorafenib treatment for advanced hepatocellular carcinoma: report of a workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan. Oncology. 2014;87(Suppl 1):104–9.

    Article  CAS  PubMed  Google Scholar 

  10. Ikai I, Takayasu K, Omata M, Liver Cancer Study Group of Japan, et al. A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol. 2006;41:884–92.

    Article  PubMed  Google Scholar 

  11. Reig M, Torres F, Rodriguez-Lope C, et al. Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib. J Hepatol. 2014;61:318–24.

    Article  CAS  PubMed  Google Scholar 

  12. Personeni N, Bozzarelli S, Pressiani T, et al. Usefulness of alpha-fetoprotein response in patients treated with sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2012;57:101–7.

    Article  CAS  PubMed  Google Scholar 

  13. Edeline J, Boucher E, Rolland Y, et al. Comparison of tumor response by response evaluation criteria in solid tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer. 2012;118:147–56.

    Article  CAS  PubMed  Google Scholar 

  14. Sieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: modalities, indication, and patient selection. J Hepatol. 2015;62:1187–95.

    Article  PubMed  Google Scholar 

  15. Hayashi H, Beppu T, Okabe H, et al. Functional assessment versus conventional volumetric assessment in the prediction of operative outcomes after major hepatectomy. Surgery. 2015;157:20–6.

    Article  PubMed  Google Scholar 

  16. Imai K, Beppu T, Chikamoto A, et al. Comparison between hepatic resection and radiofrequency ablation as first-line treatment for solitary small-sized hepatocellular carcinoma of 3 cm or less. Hepatol Res. 2013;43:853–64.

    Article  PubMed  Google Scholar 

  17. Okabe K, Beppu T, Haraoka K, et al. Safety and short-term therapeutic effects of miriplatin–lipiodol suspension in transarterial chemoembolization (TACE) for hepatocellular carcinoma. Anticancer Res. 2011;31:2983–8.

    CAS  PubMed  Google Scholar 

  18. Sugiyama S, Beppu T, Ishiko T, et al. Efficacy of radiotherapy for PV and IVC tumor thrombosis in unresectable HCC. Hepatogastroenterology. 2007;54:1779–82.

    CAS  PubMed  Google Scholar 

  19. Katz MH. Multivariable analysis: a practical guide for clinicians and public health researchers. Cambridge: Cambridge University Press; 2011. p. 139.

    Book  Google Scholar 

  20. Nakamura K, Beppu T, Hayashi H, et al. Recurrence-free survival of hepatocellular carcinoma patient with tumor thrombosis of the inferior vena cava after treatment with sorafenib and hepatic resection. Int Surg. 2015;100:908–14.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Nitta H, Beppu T, Imai K, et al. Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion. World J Surg. 2013;37:1034–42.

    Article  PubMed  Google Scholar 

  22. Sakamoto K, Beppu T, Hayashi H, et al. Antiviral therapy and long-term outcome for hepatitis B virus-related hepatocellular carcinoma after curative liver resection in a Japanese cohort. Anticancer Res. 2015;35:1647–55.

    PubMed  Google Scholar 

  23. Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol. 2015;21:3826–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lee HS, Choi GH, Choi JS, et al. Surgical resection after down-staging of locally advanced hepatocellular carcinoma by localized concurrent chemoradiotherapy. Ann Surg Oncol. 2014;21:3646–53.

    Article  PubMed  Google Scholar 

  25. Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol. 2013;24:2484–92.

    Article  CAS  PubMed  Google Scholar 

  26. Fukuchi M, Ishiguro T, Ogata K, et al. Prognostic role of conversion surgery for unresectable gastric cancer. Ann Surg Oncol. 2015;22:3618–24.

    Article  PubMed  Google Scholar 

  27. Beppu T, Miyamoto Y, Sakamoto Y, et al. Chemotherapy and targeted therapy for patients with initially unresectable colorectal liver metastases, focusing on conversion hepatectomy and long-term survival. Ann Surg Oncol. 2014;21(Suppl 3):S405–13.

    Article  PubMed  Google Scholar 

  28. Barbier L, Muscari F, Le Guellec S, et al. Liver resection after downstaging hepatocellular carcinoma with sorafenib. Int J Hepatol. 2011;2011:791013. doi:10.4061/2011/791013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Irtan S, Chopin-Laly X, Ronot M, et al. Complete regression of locally advanced hepatocellular carcinoma induced by sorafenib allowing curative resection. Liver Int. 2011;31:740–3.

    Article  PubMed  Google Scholar 

  30. Curtit E, Thiery-Vuillemin A, Nguyen T, et al. Complete histologic response induced by sorafenib in advanced hepatocellular carcinoma: a case report. J Clin Oncol. 2011;29:e330–2.

    Article  PubMed  Google Scholar 

  31. Kitajima T, Hatano E, Mitsunori Y, et al. Complete pathological response induced by sorafenib for advanced hepatocellular carcinoma with multiple lung metastases and venous tumor thrombosis allowing for curative resection. Clin J Gastroenterol. 2015;8:300–5.

    Article  PubMed  Google Scholar 

  32. Moore M, Hirte HW, Siu L, et al. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol. 2005;16:1688–94.

    Article  CAS  PubMed  Google Scholar 

  33. Mellor JD, Cassumbhoy M, Jefford M. Clinical guidance on the perioperative use of targeted agents in solid tumor oncology. Asia Pac J Clin Oncol. 2011;7:106–13.

    Article  PubMed  Google Scholar 

  34. Beckwith C, Tyler L, editors. Cancer Chemotherapy Manual 2007. Salt Lake City: Wolters Kluwer Health University of Utah; 2007.

    Google Scholar 

  35. Cowey CL, Amin C, Pruthi RS, et al. Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol. 2010;28:1502–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Eng FCS, Easson AM, Szentgyorgyi E, et al. Sorafenib and surgical complications: a case report of adverse reaction to sorafenib during treatment for renal cell carcinoma. Eur J Surg Oncol. 2009;35:219–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This manuscript has not been published and is not under consideration for publication elsewhere. All of the authors have read the manuscript and have approved this submission.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan

    Hideaki Takeyama, Toru Beppu, Takaaki Higashi, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Katsunori Imai, Hidetoshi Nitta, Hiromitsu Hayashi, Shigeki Nakagawa, Hirohisa Okabe, Daisuke Hashimoto, Akira Chikamoto, Takatoshi Ishiko & Hideo Baba

  2. Department of Gastroenterology and Hepatology, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan

    Motohiko Tanaka & Yutaka Sasaki

Authors
  1. Hideaki Takeyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toru Beppu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takaaki Higashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takayoshi Kaida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kota Arima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katsunobu Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Katsunori Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hidetoshi Nitta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiromitsu Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shigeki Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hirohisa Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Daisuke Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Akira Chikamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takatoshi Ishiko
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Motohiko Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yutaka Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hideo Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideo Baba.

Ethics declarations

Funding

This study received no financial support.

Conflict of interest

The authors report no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takeyama, H., Beppu, T., Higashi, T. et al. Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma. Surg Today 48, 431–438 (2018). https://doi.org/10.1007/s00595-017-1603-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-017-1603-x

Keywords

Search

Navigation