Journal of Gastroenterology

, Volume 46, Issue 7, pp 913–920

The effectiveness of particle radiotherapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus

  • Shohei Komatsu
  • Takumi Fukumoto
  • Yusuke Demizu
  • Daisuke Miyawaki
  • Kazuki Terashima
  • Yasue Niwa
  • Masayuki Mima
  • Osamu Fujii
  • Ryohei Sasaki
  • Isamu Yamada
  • Yuichi Hori
  • Yoshio Hishikawa
  • Mitsuyuki Abe
  • Yonson Ku
  • Masao Murakami
Original Article—Liver, Pancreas, and Biliary Tract



The prognosis of patients who have hepatocellular carcinoma (HCC) associated with inferior vena cava tumor thrombus (IVCTT) is very poor, and effective treatment modalities are extremely limited. The objective of this study was to determine the therapeutic efficacy of particle radiotherapy for HCC with IVCTT.


Between June 2001 and January 2009, 16 evaluable patients who had HCC with IVCTT were treated with particle radiotherapy. They were divided into 2 groups: 6 were treated with curative intent; 10 with palliative intent. The local tumor control rates, overall survival rates, and toxicities were evaluated.


All tumors treated with particle radiotherapy remained controlled without local recurrence at the last follow-up. The overall survival rates for the 16 patients at 1 and 3 years were 61.1 and 36.7%, respectively. We observed a significant difference in the survival rates according to treatment policy. The median survival time was 25.4 months for patients treated with curative intent and 7.7 months for those treated with palliative intent. The one-year survival rates were 100.0 and 33.3%, respectively. No Grade 3 or higher treatment-related toxicities were observed.


Particle radiotherapy is thought to be potentially effective and safe for HCC with IVCTT. Considering the current lack of effective and less-invasive local therapy for HCC with IVCTT, particle radiotherapy may therefore be an attractive new therapeutic approach for this type of HCC.


Hepatocellular carcinoma Inferior vena cava tumor thrombus Proton radiotherapy Carbon ion radiotherapy Particle radiotherapy 


  1. 1.
    Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.PubMedCrossRefGoogle Scholar
  2. 2.
    Pirisi M, Avellini C, Fabris C, Scott C, Bardus P, Soardo G, et al. Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study. J Cancer Res Clin Oncol. 1998;124:397–400.PubMedCrossRefGoogle Scholar
  3. 3.
    Stuart KE, Anand AJ, Jenkins RL. Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer. 1996;77:2217–22.PubMedCrossRefGoogle Scholar
  4. 4.
    Fong Y, Sun RL, Jarnagin W, Blumgart LH. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg. 1999;229:790–9. (discussion 9–800).PubMedCrossRefGoogle Scholar
  5. 5.
    Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48(Suppl 1):S20–37.PubMedCrossRefGoogle Scholar
  6. 6.
    Nagasue N, Yukaya H, Hamada T, Hirose S, Kanashima R, Inokuchi K. The natural history of hepatocellular carcinoma. A study of 100 untreated cases. Cancer. 1984;54:1461–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Winterbauer RH, Elfenbein IB, Ball WC Jr. Incidence and clinical significance of tumor embolization to the lungs. Am J Med. 1968;45:271–90.PubMedCrossRefGoogle Scholar
  8. 8.
    Kashima Y, Miyazaki M, Ito H, Kaiho T, Nakagawa K, Ambiru S, et al. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein. J Gastroenterol Hepatol. 1999;14:922–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Chern MC, Chuang VP, Cheng T, Lin ZH, Lin YM. Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma with inferior vena cava and right atrial tumors. Cardiovasc Intervent Radiol. 2008;31:735–44.PubMedCrossRefGoogle Scholar
  10. 10.
    Lu DS, Raman SS, Limanond P, Aziz D, Economou J, Busuttil R, et al. Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors. J Vasc Interv Radiol. 2003;14:1267–74.PubMedGoogle Scholar
  11. 11.
    Berber E, Siperstein A. Local recurrence after laparoscopic radiofrequency ablation of liver tumors: an analysis of 1032 tumors. Ann Surg Oncol. 2008;15:2757–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Fukuda S, Okuda K, Imamura M, Imamura I, Eriguchi N, Aoyagi S. Surgical resection combined with chemotherapy for advanced hepatocellular carcinoma with tumor thrombus: report of 19 cases. Surgery. 2002;131:300–10.PubMedCrossRefGoogle Scholar
  13. 13.
    Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedGoogle Scholar
  14. 14.
    Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys. 1995;31:1237–48.PubMedCrossRefGoogle Scholar
  15. 15.
    Dawson LA. Protons or photons for hepatocellular carcinoma? Let’s move forward together. Int J Radiat Oncol Biol Phys. 2009;74:661–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Schulz-Ertner D, Tsujii H. Particle radiation therapy using proton and heavier ion beams. J Clin Oncol. 2007;25:953–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Greco C, Wolden S. Current status of radiotherapy with proton and light ion beams. Cancer. 2007;109:1227–38.PubMedCrossRefGoogle Scholar
  18. 18.
    Hata M, Tokuuye K, Sugahara S, Kagei K, Igaki H, Hashimoto T, et al. Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus. Cancer. 2005;104:794–801.PubMedCrossRefGoogle Scholar
  19. 19.
    Chiba T, Tokuuye K, Matsuzaki Y, Sugahara S, Chuganji Y, Kagei K, et al. Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients. Clin Cancer Res. 2005;11:3799–805.PubMedCrossRefGoogle Scholar
  20. 20.
    Kawashima M, Furuse J, Nishio T, Konishi M, Ishii H, Kinoshita T, et al. Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol. 2005;23:1839–46.PubMedCrossRefGoogle Scholar
  21. 21.
    Bush DA, Hillebrand DJ, Slater JM, Slater JD. High-dose proton beam radiotherapy of hepatocellular carcinoma: preliminary results of a phase II trial. Gastroenterology. 2004;127:S189–93.PubMedCrossRefGoogle Scholar
  22. 22.
    Nakayama H, Sugahara S, Tokita M, Fukuda K, Mizumoto M, Abei M, et al. Proton beam therapy for hepatocellular carcinoma: the University of Tsukuba experience. Cancer. 2009;115:5499–506.PubMedCrossRefGoogle Scholar
  23. 23.
    Kato H, Tsujii H, Miyamoto T, Mizoe JE, Kamada T, Tsuji H, et al. Results of the first prospective study of carbon ion radiotherapy for hepatocellular carcinoma with liver cirrhosis. Int J Radiat Oncol Biol Phys. 2004;59:1468–76.PubMedCrossRefGoogle Scholar
  24. 24.
    Greene FL, Page DL, Fleming ID. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002.CrossRefGoogle Scholar
  25. 25.
    Mayahara H, Murakami M, Kagawa K, Kawaguchi A, Oda Y, Miyawaki D, et al. Acute morbidity of proton therapy for prostate cancer: the Hyogo Ion Beam Medical Center experience. Int J Radiat Oncol Biol Phys. 2007;69:434–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Yamada K, Izaki K, Sugimoto K, Mayahara H, Morita Y, Yoden E, et al. Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2003;57:113–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim TH, Kim DY, Park JW, Kim SH, Choi JI, Kim HB, et al. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2007;67:225–31.PubMedCrossRefGoogle Scholar
  28. 28.
    Mizumoto M, Tokuuye K, Sugahara S, Nakayama H, Fukumitsu N, Ohara K, et al. Proton beam therapy for hepatocellular carcinoma adjacent to the porta hepatis. Int J Radiat Oncol Biol Phys. 2008;71:462–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31:1341–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Asahara T, Itamoto T, Katayama K, Nakahara H, Hino H, Yano M, et al. Hepatic resection with tumor thrombectomy for hepatocellular carcinoma with tumor thrombi in the major vasculatures. Hepatogastroenterology. 1999;46:1862–9.PubMedGoogle Scholar
  31. 31.
    Peng SY, Cai XJ, Mu YP, Hong DF, Xu B, Qian HR, et al. Surgical treatment of hepatocellular carcinoma with tumor thrombus in inferior vena cava. Zhonghua Wai Ke Za Zhi. 2006;44:878–81.PubMedGoogle Scholar
  32. 32.
    Liu CL, Fan ST, Cheung ST, Lo CM, Ng IO, Wong J. Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study. Ann Surg. 2006;244:194–203.PubMedCrossRefGoogle Scholar
  33. 33.
    Kaseb AO, Hanbali A, Cotant M, Hassan MM, Wollner I, Philip PA. Vascular endothelial growth factor in the management of hepatocellular carcinoma: a review of literature. Cancer. 2009;115:4895–906.PubMedCrossRefGoogle Scholar
  34. 34.
    Chau GY, Lui WY, Chi CW, Chau YP, Li AF, Kao HL, et al. Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection. Eur J Surg Oncol. 2008;34:333–8.PubMedGoogle Scholar
  35. 35.
    Qin LX, Tang ZY. The prognostic molecular markers in hepatocellular carcinoma. World J Gastroenterol. 2002;8:385–92.PubMedGoogle Scholar
  36. 36.
    Tse RV, Guha C, Dawson LA. Conformal radiotherapy for hepatocellular carcinoma. Crit Rev Oncol Hematol. 2008;67:113–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Cheng JC, Wu JK, Huang CM, Liu HS, Huang DY, Tsai SY, et al. Dosimetric analysis and comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy for patients with hepatocellular carcinoma and radiation-induced liver disease. Int J Radiat Oncol Biol Phys. 2003;56:229–34.PubMedCrossRefGoogle Scholar
  38. 38.
    Zeng ZC, Fan J, Tang ZY, Zhou J, Qin LX, Wang JH, et al. A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys. 2005;61:432–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Zeng ZC, Fan J, Tang ZY, Zhou J, Wang JH, Wang BL, et al. Prognostic factors for patients with hepatocellular carcinoma with macroscopic portal vein or inferior vena cava tumor thrombi receiving external-beam radiation therapy. Cancer Sci. 2008;99:2510–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106:1653–63.PubMedCrossRefGoogle Scholar
  41. 41.
    Koo JE, Kim JH, Lim YS, Park SJ, Won HJ, Sung KB, et al. Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys. 2009;78(1):180–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Shohei Komatsu
    • 1
  • Takumi Fukumoto
    • 1
  • Yusuke Demizu
    • 2
  • Daisuke Miyawaki
    • 3
  • Kazuki Terashima
    • 2
  • Yasue Niwa
    • 2
  • Masayuki Mima
    • 2
  • Osamu Fujii
    • 2
  • Ryohei Sasaki
    • 3
  • Isamu Yamada
    • 1
  • Yuichi Hori
    • 1
  • Yoshio Hishikawa
    • 2
  • Mitsuyuki Abe
    • 2
  • Yonson Ku
    • 1
  • Masao Murakami
    • 2
  1. 1.Division of Hepato-Biliary-Pancreatic Surgery, Department of SurgeryKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of RadiologyHyogo Ion Beam Medical CenterTatsunoJapan
  3. 3.Division of Radiation Oncology, Department of RadiologyKobe University Graduate School of MedicineKobeJapan

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