Hepatobiliary Malignancies

  • Kyle Wang
  • Andrew Z. Wang
  • Joel E. Tepper


Historically, the radiosensitivity of hepatocytes and risk for radiation-induced liver disease (RILD) precluded the use of RT for liver tumors using older techniques. CT-based planning, SBRT, and IMRT have generated renewed interest in the treatment of liver malignancies due to the new ability to deliver high doses to tumors with good normal tissue sparing. Though surgery is the primary treatment modality for liver tumors, RT provides previously unavailable opportunities for durable local control in patients who are inoperable or not candidates for other ablative approaches. Here, we review hypofractionated RT (focusing on SBRT) for hepatocellular carcinoma (HCC), cholangiocarcinoma (predominantly intrahepatic and perihilar types), and liver metastases. Though distinct clinical entities, the principles of SBRT delivery are similar, though cirrhosis commonly impacts dose delivery in patients with HCC.


Liver Bile duct Hepatocellular carcinoma Cholangiocarcinoma Liver metastases SBRT 


  1. 1.
    Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362(9399):1907–17.CrossRefPubMedGoogle Scholar
  2. 2.
    Abe T, Saitoh J, Kobayashi D, et al. Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma. Radiat Oncol. 2015;10:187.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gandhi SJ, Liang X, Ding X, et al. Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: photons versus protons. Pract Radiat Oncol. 2015;5(4):209–18.CrossRefPubMedGoogle Scholar
  4. 4.
    Brade AM, Ng S, Brierley J, et al. Phase 1 trial of sorafenib and stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2016;94(3):580–7.CrossRefPubMedGoogle Scholar
  5. 5.
    NCCN Hepatobiliary. Hepatobiliary Cancers (Version 2.2016). 2016. Accessed 18 Oct 2016.
  6. 6.
    NCCN Colon. Colon Cancer (Version 2.2016). 2016. Accessed 18 Oct 2016.
  7. 7.
    Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol. 2006;45(7):823–30.CrossRefPubMedGoogle Scholar
  8. 8.
    Huertas A, Baumann AS, Saunier-Kubs F, et al. Stereotactic body radiation therapy as an ablative treatment for inoperable hepatocellular carcinoma. Radiother Oncol. 2015;115(2):211–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118(21):5424–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009;27(10):1572–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Vautravers-Dewas C, Dewas S, Bonodeau F, et al. Image-guided robotic stereotactic body radiation therapy for liver metastases: is there a dose response relationship? Int J Radiat Oncol Biol Phys. 2011;81(3):e39–47.CrossRefPubMedGoogle Scholar
  12. 12.
    Yoon SM, Lim YS, Park MJ, et al. Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS One. 2013;8(11):e79854.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Takeda A, Sanuki N, Tsurugai Y, et al. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer. 2016;122(13):2041–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Andolino DL, Johnson CS, Maluccio M, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011;81(4):e447–53.CrossRefPubMedGoogle Scholar
  15. 15.
    Kopek N, Holt MI, Hansen AT, Hoyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol. 2010;94(1):47–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Mahadevan A, Dagoglu N, Mancias J, et al. Stereotactic body radiotherapy (SBRT) for intrahepatic and hilar cholangiocarcinoma. J Cancer. 2015;6(11):1099–104.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kimura T, Aikata H, Takahashi S, et al. Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies. Hepatol Res. 2015;45(4):378–86.CrossRefPubMedGoogle Scholar
  18. 18.
    Bujold A, Massey CA, Kim JJ, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31(13):1631–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Lee MT, Kim JJ, Dinniwell R, et al. Phase I study of individualized stereotactic body radiotherapy of liver metastases. J Clin Oncol. 2009;27(10):1585–91.CrossRefPubMedGoogle Scholar
  20. 20.
    Tse RV, Hawkins M, Lockwood G, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2008;26(4):657–64.CrossRefPubMedGoogle Scholar
  21. 21.
    Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34(3):219–26.CrossRefPubMedGoogle Scholar
  22. 22.
    Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37(8):4078–101.CrossRefPubMedGoogle Scholar
  23. 23.
    Pan CC, Kavanagh BD, Dawson LA, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–100.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Goldsmith C, Price P, Cross T, Loughlin S, Cowley I, Plowman N. Dose-volume histogram analysis of stereotactic body radiotherapy treatment of pancreatic cancer: a focus on duodenal dose constraints. Semin Radiat Oncol. 2016;26(2):149–56.CrossRefPubMedGoogle Scholar
  25. 25.
    Wahl DR, Stenmark MH, Tao Y, et al. Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma. J Clin Oncol. 2016;34(5):452–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Berber B, Ibarra R, Snyder L, et al. Multicentre results of stereotactic body radiotherapy for secondary liver tumours. HPB (Oxford). 2013;15(11):851–7.CrossRefGoogle Scholar
  27. 27.
    Chang DT, Swaminath A, Kozak M, et al. Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. Cancer. 2011;117(17):4060–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Eriguchi T, Takeda A, Sanuki N, et al. Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system. Int J Radiat Oncol Biol Phys. 2013;85(4):1006–11.CrossRefPubMedGoogle Scholar
  29. 29.
    Klein J, Dawson LA, Jiang H, et al. Prospective longitudinal assessment of quality of life for liver cancer patients treated with stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys. 2015;93(1):16–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys. 2002;53(4):810–21.CrossRefPubMedGoogle Scholar
  31. 31.
    Kim TH, Kim DY, Park JW, 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(1):225–31.CrossRefPubMedGoogle Scholar
  32. 32.
    Xu ZY, Liang SX, Zhu J, et al. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma. Int J Radiat Oncol Biol Phys. 2006;65(1):189–95.CrossRefPubMedGoogle Scholar
  33. 33.
    Polistina FA, Guglielmi R, Baiocchi C, et al. Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol. 2011;99(2):120–3.CrossRefPubMedGoogle Scholar
  34. 34.
    Welling TH, Feng M, Wan S, et al. Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma. Liver Transpl. 2014;20(1):81–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Barney BM, Olivier KR, Miller RC, Haddock MG. Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma. Radiat Oncol. 2012;7:67.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Scorsetti M, Comito T, Tozzi A, et al. Final results of a phase II trial for stereotactic body radiation therapy for patients with inoperable liver metastases from colorectal cancer. J Cancer Res Clin Oncol. 2015;141(3):543–53.CrossRefPubMedGoogle Scholar
  37. 37.
    Katz AW, Carey-Sampson M, Muhs AG, Milano MT, Schell MC, Okunieff P. Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys. 2007;67(3):793–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Kyle Wang
    • 1
  • Andrew Z. Wang
    • 1
  • Joel E. Tepper
    • 1
  1. 1.Department of Radiation OncologyUniversity of North Carolina HospitalsChapel HillUSA

Personalised recommendations