Tumor Biology

, Volume 36, Issue 7, pp 4967–4972 | Cite as

The comparison of outcomes between hypofractionated and conventional 3D-CRT regimens used in combination with TACE as first-line treatment of advanced hepatocellular carcinoma

  • Chuanxi Wang
  • Suping Li
  • Aimin Sun
  • Longhua Chen
  • Rongxiang Liang
  • Guanzhen Li
  • Junqing Han
Research Article


Treatment of primary hepatocellular carcinoma (HCC) with transcatheter hepatic arterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) achieves good short-term but poor long-term survival. We retrospectively assessed whether outcomes differ between hypofractionated and conventional 3D-CRT regimens. Patients were treated in our institution between June 2005 and October 2009. All patients received two cycles of TACE followed by either hypofractionated 3D-CRT (6–8 Gy fractions for 3–4 weeks to 48–64 Gy) or conventional 3D-CRT (2 Gy fractions for 6–7 weeks to 60–70 Gy) 4 weeks later. We assessed data from 110 patients (55 in each 3D-CRT group). Overall response rates were similar in the two groups. Acute adverse event rates were not significantly higher in the hypofractionated 3D-CRT group than in the conventional 3D-CRT group; two patients and one patient, respectively, died of late radiation-induced liver failure. Overall survival at 1 year was 83.6 % in the hypofractionated 3D-CRT group versus 68.8 % in the conventional 3D-CRT group (P = 0.019), and at 3 years, it was 31.7 versus 13.9 % (P = 0.004). Median survival was 27.97 versus 16.13 months (P = 0.002). Hypofractionated 3D-CRT seemed to provide better overall survival than conventional 3D-CRT regimens combined with TACE as a first-line treatment for advanced HCC.


Hepatocellular carcinoma Radiotherapy Three-dimensional conformal radiotherapy Transcatheter hepatic arterial chemoembolization 



This study was supported by grants from the National Natural Science Foundation of China (nos. 30772530 and 81272507) and the Natural Science Foundation of Shandong Province (2009ZRC03099 and BS2013YY048) and a grant provided by Jinan, Shandong Province (201221015).

Conflicts of interest



  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Di Bisceglie AM. Issues in screening and surveillance for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S104–7.CrossRefPubMedGoogle Scholar
  3. 3.
    He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, et al. Major causes of death among men and women in China. N Engl J Med. 2005;353(11):1124–34.CrossRefPubMedGoogle Scholar
  4. 4.
    Nakashima O, Kojiro M. Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology. J Hepato-Biliary-Pancreat Surg. 2001;8(5):404–9.CrossRefGoogle Scholar
  5. 5.
    Bolondi L. Screening for hepatocellular carcinoma in cirrhosis. J Hepatol. 2003;39(6):1076–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Morris-Stiff G, Gomez D, de Liguori CN, Prasad KR. Surgical management of hepatocellular carcinoma: is the jury still out? Surg Oncol. 2009;18(4):298–321.CrossRefPubMedGoogle Scholar
  7. 7.
    Cheng JC, Chuang VP, Cheng SH, Huang AT, Lin YM, Cheng TI, et al. Local radiotherapy with or without transcatheter arterial chemoembolization for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2000;47(2):435–42.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhou ZH, Liu LM, Chen WW, Men ZQ, Lin JH, Chen Z, et al. Combined therapy of transcatheter arterial chemoembolisation and three-dimensional conformal radiotherapy for hepatocellular carcinoma. Br J Radiol. 2007;80(951):194–201.CrossRefPubMedGoogle Scholar
  9. 9.
    Merle P, Mornex F. [Transarterial chemoembolization and conformal radiotherapy for hepatocellular carcinoma]. Cancer Radiother. 2011;15(1):69–71.CrossRefPubMedGoogle Scholar
  10. 10.
    Xu LT, Zhou ZH, Lin JH, Chen Z, Wang K, Wang P, et al. Clinical study of transarterial chemoembolization combined with 3-dimensional conformal radiotherapy for hepatocellular carcinoma. Eur J Surg Oncol. 2011;37(3):245–51.CrossRefPubMedGoogle Scholar
  11. 11.
    Oh D, Lim do H, Park HC, Paik SW, Koh KC, Lee JH, et al. Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity. Am J Clin Oncol. 2010;33(4):370–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Bush DA, Kayali Z, Grove R, Slater JD. The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer. 2011;117(13):3053–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62(740):679–94.CrossRefPubMedGoogle Scholar
  14. 14.
    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(5):1341–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Yoon SM, Lim YS, Won HJ, Kim JH, Kim KM, Lee HC, et al. Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. Int J Radiat Oncol Biol Phys. 2012;82(5):2004–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Fang Y, Chen W, Liang X, Li D, Lou H, Chen R, Wang K, Pan H: Comparison of long-term effectiveness and complications of radiofrequency ablation with hepatectomy for small hepatocellular carcinoma. J Gastroenterol Hepatol 2013. doi:  10.1111/jgh.12441.
  17. 17.
    Tang QH, Li AJ, Yang GM, Lai EC, Zhou WP, Jiang ZH, et al. Surgical resection versus conformal radiotherapy combined with TACE for resectable hepatocellular carcinoma with portal vein tumor thrombus: a comparative study. World J Surg. 2013;37(6):1362–70.CrossRefPubMedGoogle Scholar
  18. 18.
    Li B, Yu J, Wang L, Li C, Zhou T, Zhai L, et al. Study of local three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for patients with stage III hepatocellular carcinoma. Am J Clin Oncol. 2003;26(4):e92–9.PubMedGoogle Scholar
  19. 19.
    Seong J, Keum KC, Han KH, Lee DY, Lee JT, Chon CY, et al. Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 1999;43(2):393–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Guo WJ, Yu EX. Evaluation of combined therapy with chemoembolization and irradiation for large hepatocellular carcinoma. Br J Radiol. 2000;73(874):1091–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Dawson LA. The evolving role of radiation therapy in hepatocellular carcinoma. Cancer Radiother. 2008;12(2):96–101.CrossRefPubMedGoogle Scholar
  22. 22.
    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(9):1839–46.CrossRefPubMedGoogle Scholar
  23. 23.
    Fukumitsu N, Sugahara S, Nakayama H, Fukuda K, Mizumoto M, Abei M, et al. A prospective study of hypofractionated proton beam therapy for patients with hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2009;74(3):831–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Park JH, Yoon SM, Lim YS, Kim SY, Shim JH, Kim KM, et al. Two-week schedule of hypofractionated radiotherapy as a local salvage treatment for small hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28(10):1638–42.PubMedGoogle Scholar
  25. 25.
    Bae SH, Park HC, Lim do H, Lee JA, Gwak GY, Choi MS, et al. Salvage treatment with hypofractionated radiotherapy in patients with recurrent small hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012;82(4):e603–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Ma H, Guo R, Yu L, Zhang Y, Ren J. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J. 2011;32(8):1025–38.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of OncologyProvincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Institution of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouChina
  3. 3.Department of Radiation Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouChina

Personalised recommendations