Skip to main content
SpringerLink
Log in

The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT)

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC) unsuitable for standard loco-regional therapies.

Materials and methods

Patients with 1–3 inoperable HCC lesions with diameter ≤6 cm were treated by SBRT. According to lesions size and liver function, two prescription regimens were adopted: 48–75 Gy in three fractions or 36–60 Gy in six fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points of this study were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and progression-free survival (PFS).

Results

Forty-three patients with 63 HCC lesions were irradiated. All patients had Child–Turcotte–Pugh class A or B disease. Thirty lesions (48 %) were treated with 48–75 Gy in three consecutive fractions, and 33 (52 %) received 36–60 Gy in six fractions. Median follow-up was 8 months (range 3–43 months). Actuarial LC at 6, 12 and 24 months was 94.2 ± 3.3, 85.8 ± 5.5 and 64.4 ± 11.5 %, respectively. A biological equivalent dose (BED) >100 Gy and GTV size were significant prognostic factors for LC in univariate analysis (p < 0.001 and p < 0.02). Median OS was 18.0 ± 5.8 months. Actuarial OS at 6, 12 and 24 months was 91.1 ± 4.9, 77.9 ± 8.2 and 45.3 ± 14.0 %, respectively. Univariate analysis showed that OS is correlated with LC (p < 0.04), BED >100 (p < 0.05) and cumulative gross tumor volume GTV <5 cm (p < 0.04). Median PFS was 8 months, with a 1-year PFS rate of 41 %. A significant (≥grade 3) toxicity was observed in seven patients (16 %) 2–6 months after the completion of the treatment. No classic radiation-induced liver disease was observed.

Conclusion

Stereotactic body radiation therapy is a safe and effective therapeutic option for HCC lesions unsuitable to standard loco-regional therapies, with acceptable local control rates and low treatment-related toxicity. The significant correlation between LC and higher doses and between LC and OS supports the clinical value of SBRT in these patients.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Andolino DL, Johnson CS, Maluccio M et al (2011) Stereotactic body radio-therapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 81:e447–e453

    Article  PubMed  Google Scholar 

  • Bibault JE, Dewas S, Vautravers-Dewas C et al (2013) Stereotactic body radiation therapy for hepatocellular carcinoma: prognostic factors of local control, overall survival, and toxicity. PLoS One 8:e77472

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bujold A, Massey CA, Kim JJ et al (2012) Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 44:1659

    Google Scholar 

  • Cardenes HR, Price TR, Perkins SM et al (2010) Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma. Clin Transl Oncol 12:218–225

    Article  CAS  PubMed  Google Scholar 

  • Cheng AL, Kang YK, Chen Z et al (2009) 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 10:25–34

    Article  CAS  PubMed  Google Scholar 

  • Choi BO, Choi IB, Jang HS et al (2008) Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer 8:351

    Article  PubMed Central  PubMed  Google Scholar 

  • Culleton S, Jiang H, Haddad CR et al (2014) Outcomes following definitive stereotactic body radiotherapy for patients with Child–Turcotte–Pugh B or C hepatocellular carcinoma. Radiother Oncol 111:412–417

    Article  PubMed  Google Scholar 

  • Dawson LA, Normolle D, Balter JM, McGinn C, Lawrence T, Ten Haken R (2002) Analysis of radiation induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53:810–821

    Article  PubMed  Google Scholar 

  • Dewas S, Bibault JE, Mirabel X et al (2012) Prognostic factors affecting local control of hepatic tumors treated by stereotactic body radiation therapy. Radiat Oncol 7:166

    Article  PubMed Central  PubMed  Google Scholar 

  • Eisenhauer E, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  • Eriguchi T, Takeda A, Sanuki N et al (2013) Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system. Int J Radiat Oncol Biol Phys 85:1006–1011

    Article  PubMed  Google Scholar 

  • European Association for the Study of the Liver and European Organisation for Research and Treatment of Cancer (2012) EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943

    Article  Google Scholar 

  • Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  CAS  PubMed  Google Scholar 

  • Goodman KA, Wiegner EA, Maturen KE et al (2010) Dose-escalation study of single-fraction stereotactic body radiotherapy for liver malignancies. Int J Radiat Oncol Biol Phys 78:486–493

    Article  PubMed  Google Scholar 

  • Herfarth KK, Debus J, Lohr F et al (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170

    CAS  PubMed  Google Scholar 

  • Huang WY, Jen YM, Lee MS et al (2012) Stereotactic body radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 84:355–361

    Article  PubMed  Google Scholar 

  • Jacob R, Turley F, Redden D et al (2014) Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥3 cm. HPB, Oxford

    Google Scholar 

  • Kang JK, Kim MS, Cho CK et al (2012) Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer 118:5424–5431

    Article  PubMed  Google Scholar 

  • Klein J, Dawson LA (2013) Hepatocellular carcinoma radiation therapy: review of evidence and future opportunities. Int J Radiat Oncol Biol Phys 87:22–32

    Article  PubMed  Google Scholar 

  • Kwon JH, Bae SH, Kim JY et al (2010) Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer. BMC Cancer 10:475

    Article  PubMed Central  PubMed  Google Scholar 

  • Lawrence TS, Robertson JM, Anscher MS, Jirtle R, Ensminger W, Fajardo L (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31:1237–1248

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Fuster J, Bruix J (1999) Intention-to treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390

    Article  CAS  PubMed  Google Scholar 

  • Llower JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442

    Article  Google Scholar 

  • Mendez Romero A, Wunderink W, Hussain SM et al (2006) Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I–II study. Acta Oncol 45:831–837

    Article  PubMed  Google Scholar 

  • Oliveri RS, Wetterslev J, Gluud C (2011) Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 3:CD004787

  • Park JH, Yoon SM, Lim YS et al (2013) Two-week schedule of hypofractionated radiotherapy as a local salvage treatment for small hepatocellular carcinoma. J Gastroenterol Hepatol 28:1638–1642

    PubMed  Google Scholar 

  • Que JY, Lin LC, Lin KL, Lin CH, Lin YW, Yang CC (2014) The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities. Radiat Oncol 9:120

    Article  PubMed Central  PubMed  Google Scholar 

  • Sanuki N, Takeda A, Oku Y et al (2014a) Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol 53:399–404

    Article  PubMed  Google Scholar 

  • Sanuki N, Takeda A, Kunieda E et al (2014b) Role of stereotactic body radiation therapy for hepatocellular carcinoma. World J Gastroenterol 20:3100–3111

    Article  PubMed Central  PubMed  Google Scholar 

  • Scorsetti M, Arcangeli S, Tozzi A, Comito T, Alongi F, Navarria P (2013) Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial. Int J Radiat Oncol Biol Phys 86:336–342

  • Seo YS, Kim MS, Yoo SY et al (2010) Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Oncol 102:209–214

    Article  PubMed  Google Scholar 

  • Tse RV, Hawkins M, Lockwood G et al (2008) Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 26:657–664

    Article  PubMed  Google Scholar 

  • Xi M, Zhang L, Zhao L et al (2013) Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One 8:e63864

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhong NB, Lv GM, Chen ZH (2014) Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (≥10 cm) hepatocellular carcinomas: a clinical study. Mol Clin Oncol 2:839–844

    PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

L. Cozzi acts as Scientific Advisor to Varian Medical Systems and is Clinical Research Scientist at Humanitas cancer center. All other co-authors have no conflicts of interests.

Author information

Authors and Affiliations

  1. Radiotherapy and Radiosurgery, Oncology, Liver Surgery, Hepatology Departments, Humanitas Clinical and Research Center, Rozzano, MI, Italy

    Marta Scorsetti, Tiziana Comito, Luca Cozzi, Elena Clerici, Angelo Tozzi, Ciro Franzese, Pierina Navarria, Stefano Tomatis, Giuseppo D’Agostino, Cristina Iftode, Pietro Mancosu, Roberto Ceriani & Guido Torzilli

  2. Medical Physics Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Antonella Fogliata

  3. Humanitas Research Hospital, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano, MI, Italy

    Luca Cozzi

Authors
  1. Marta Scorsetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiziana Comito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luca Cozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Clerici
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Angelo Tozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ciro Franzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pierina Navarria
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonella Fogliata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stefano Tomatis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giuseppo D’Agostino
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cristina Iftode
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pietro Mancosu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Roberto Ceriani
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Guido Torzilli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luca Cozzi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scorsetti, M., Comito, T., Cozzi, L. et al. The challenge of inoperable hepatocellular carcinoma (HCC): results of a single-institutional experience on stereotactic body radiation therapy (SBRT). J Cancer Res Clin Oncol 141, 1301–1309 (2015). https://doi.org/10.1007/s00432-015-1929-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-015-1929-y

Keywords

Search

Navigation