Skip to main content
Log in

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

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

Access this article

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

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  2. Lim KC, Chow PK, Allen JC, Siddiqui FJ, Chan ES, Tan SB. Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria. Br J Surg. 2012;99:1622–9.

    Article  PubMed  Google Scholar 

  3. Kudo M, Han KH, Kokudo N, Cheng AL, Choi BI, Furuse J, et al. Liver Cancer Working Group report. Jpn J Clin Oncol. 2010;40(Suppl 1):i19–27.

    Article  PubMed  Google Scholar 

  4. Abbas A, Medvedev S, Shores N, Bazzano L, Dehal A, Hutchings J, et al. Epidemiology of metastatic hepatocellular carcinoma, a nationwide perspective. Dig Dis Sci. 2014;59:2813–20.

    Article  PubMed  Google Scholar 

  5. Uchino K, Tateishi R, Shiina S, Kanda M, Masuzaki R, Kondo Y, et al. Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer. 2011;117:4475–83.

    Article  PubMed  Google Scholar 

  6. Kojima Y, Ueno H, Okusaka T, Morizane C, Kondo S, Hagihara A, et al. Hepatocellular carcinoma presenting with lung metastasis: clinical characteristics and prognostic factors. J Clin Oncol. 2009;27:e15604.

    Google Scholar 

  7. Zhang SM, Zeng ZC, Tang ZY, Sun J, Cheng JM, Liu R, et al. Prognostic analysis of pulmonary metastases from hepatocellular carcinoma. Hepatol Int. 2008;2:237–43.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hu Z, Li W, Huang P, Zhou Z, Xu J, Xu K, et al. Therapeutic significance and indications of pulmonary metastasectomy for hepatocellular carcinoma following liver resection. Int J Surg. 2017;48:23–31.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, et al. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29:339–64.

    Article  PubMed  Google Scholar 

  11. Thomas MB, Jaffe D, Choti MM, Belghiti J, Curley S, Fong Y, et al. Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute clinical trials planning meeting. J Clin Oncol. 2010;28:3994–4005.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yoon YS, Kim HK, Kim J, Choi YS, Shim YM, Paik SW, et al. Long-term survival and prognostic factors after pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:2795–801.

    Article  PubMed  Google Scholar 

  13. Li X, Wang J, Li W, Huang Z, Fan W, Chen Y, et al. Percutaneous CT-guided radiofrequency ablation for unresectable hepatocellular carcinoma pulmonary metastases. Int J Hyperth. 2012;28:721–8.

    Article  CAS  Google Scholar 

  14. Duan F, Wang MQ, Liu FY, Wang ZJ, Song P, Wang Y. Sorafenib in combination with transarterial chemoembolization and bronchial arterial chemoinfusion in the treatment of hepatocellular carcinoma with pulmonary metastasis. Asia Pac J Clin Oncol. 2012;8:156–63.

    Article  PubMed  Google Scholar 

  15. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  16. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, 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 

  17. Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 2012;62:394–9.

    Article  PubMed  Google Scholar 

  18. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.

    Article  PubMed  Google Scholar 

  19. Fukui H, Saito H, Ueno Y, Uto H, Obara K, Sakaida I, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51:629–50.

    Article  CAS  PubMed  Google Scholar 

  20. The Liver Cancer Study Group Of Japan. The general rules for the clinical and pathological study of primary liver cancer. 5 (revised version) ed. Tokyo: Kanehara; 2009.

    Google Scholar 

  21. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  22. Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011;10:150–61.

    Article  PubMed  Google Scholar 

  23. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083–107.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gwak GY, Jung JO, Sung SW, Lee HS. Long-term survival after pulmonary metastatectomy of hepatocellular carcinoma; treatment outcome or natural history? Hepatogastroenterology. 2004;51:1428–33.

    PubMed  Google Scholar 

  25. Yau T, Chan P, Ng KK, Chok SH, Cheung TT, Fan ST, et al. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer. 2009;115:428–36.

    Article  CAS  PubMed  Google Scholar 

  26. Katafuchi E, Takami Y, Wada Y, Tateishi M, Ryu T, Mikagi K, et al. Long-term maintenance of complete response after sorafenib treatment for multiple lung metastases from hepatocellular carcinoma. Case Rep Gastroenterol. 2015;9:285–90.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ito S, Yoshimura T, Kondo T, Tamura K, Yamashita N, Hanawa T. Long-term survival with chest wall resection and pulmonary metastasectomy for hepatocellular carcinoma. Ann Thorac Surg. 2015;99:695–8.

    Article  PubMed  Google Scholar 

  28. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are very grateful to Dr. Zhiyu Xiao, Jianlong Zhang, Chuanchao He, Kai Mao, Hai Jiang, Qiaodong Xu, Yongcong Yan, Xiaoying Wu, Zhimin Yu, Zheng Chen and Qiming Zhou for clinical data collection and discussion. This study was supported by the National Natural Science Foundation of China (Grant numbers: 81502080, 81672405, 81372565), Grant from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology (Grant number: [2013]163), and Grant from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes (Grant number: K1809001).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to J. Wang or H. Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

This study was reviewed and approved by the ethics committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University and complied with the standards of the Helsinki Declaration and current ethical guidelines.

Informed consent

Informed consent was exempt because it was accomplished retrospectively and anonymously.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, Z., Huang, P., Zhou, Z. et al. Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis. Clin Transl Oncol 20, 729–739 (2018). https://doi.org/10.1007/s12094-017-1779-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-017-1779-y

Keywords

Navigation