Skip to main content
SpringerLink
Log in

Proton Beam Therapy in Liver Malignancies

  • Gastrointestinal Cancers (J Meyer, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Proton beam therapy (PBT) allows for improved sparing of surrounding normal tissues compared with X-ray-based radiation therapy. This is especially important in the setting of liver malignancies, where an increase in integral dose leads to a higher risk of radiation-induced liver disease (RILD) as well as close proximity to vital gastrointestinal (GI) organs.

Recent Findings

We have data from multiple centers demonstrating that PBT can safely deliver high, ablative doses of radiation therapy conferring excellent local control with good tolerance of treatment.

Summary

PBT is an effective treatment with longstanding evidence of efficacy that is increasing in availability.

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.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cancer of the Liver and Intrahepatic Bile Duct - Cancer Stat Facts https://seer.cancer.gov/statfacts/html/livibd.html. Accessed 11 Nov 2019.

  2. Annual Report to the Nation 2019: National Cancer Statistics https://seer.cancer.gov/report_to_nation/statistics.html#new. Accessed 11 Nov 2019.

  3. •• Tao R, 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;34:219–26. This study provides evidence for dose-escalation in the treatment of intrahepatic cholangiocarcinoma showing a statistically significant improvement of local control and overall survival with BED greater than 80.5Gy.

  4. Wulf J, Guckenberger M, Haedinger U, Oppitz U, Mueller G, Baier K, et al. Stereotactic radiotherapy of primary liver cancer and hepatic metastases. Acta Oncol. 2006;45:838–47.

    Article  Google Scholar 

  5. Lee MT, Kim JJ, Dinniwell R, Brierley J, Lockwood G, Wong R, et al. Phase I study of individualized stereotactic body radiotherapy of liver metastases. J Clin Oncol. 2009;27:1585–91.

    Article  Google Scholar 

  6. McCammon R, Schefter TE, Gaspar LE, Zaemisch R, Gravdahl D, Kavanagh B. Observation of a dose-control relationship for lung and liver tumors after stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys. 2009;73:112–8.

    Article  Google Scholar 

  7. • Velec, et al. Predictors of liver toxicity following stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2017(5):939–46. This study establishes liver dose constraints conveying the importance of sparing threshold volumes of liver from even low doses of radiation.

  8. Hsieh, et al. Predictors of radiation-induced liver disease in eastern and western patients with hepatocellular carcinoma undergoing proton beam therapy. Int J Radiat Oncol Biol Phys. 2019;105(1):73–86.

    Article  Google Scholar 

  9. Kopek N, Holt MI, Hansen AT, Hoyer M. Stereotactic body radiotherapy for unresectable cholangiocarcinoma. Radiother Oncol. 2010;94:47–52.

    Article  Google Scholar 

  10. Chiba, et al. Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients. Clin Cancer Res. 2005;11(10):3799–805.

    Article  Google Scholar 

  11. Fukumitsu, 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.

    Article  Google Scholar 

  12. Nakayama, et al. Proton beam therapy for hepatocellular carcinoma. Cancer. 2009:5499–506.

  13. Bush, et al. High-dose proton beam radiotherapy of hepatocellular carcinoma: preliminary results of a phase II trial. Gastroenterology. 2004;127:S138–93.

    Article  Google Scholar 

  14. Chadha, et al. Proton beam therapy outcomes of localized unresectable hepatocellular carcinoma. Radiother Oncol. 2019;133:54–61.

    Article  Google Scholar 

  15. Hasan, et al. Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of a biologically effective dose escalation. J Gastrointest Oncol. 2019;10(5):999–1009.

    Article  Google Scholar 

  16. • Sanford, et al. Protons versus photons for unresectable hepatocellular carcinoma: liver decompensation and overall survival. Int J Radiat Oncol Biol Phys. 2019;105(1):64–72. This retrospective study provides the foundation for pursuing large prospective studies, such as GI-003 comparing photons and protons as there is a suggestion that liver sparing with protons leads to improvements in overall survival.

  17. Hong, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol. 2015;34:460–8.

    Article  Google Scholar 

  18. Bujold, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31:1631–9.

    Article  Google Scholar 

  19. Makita C, Nakamura T, Takada A, Takayama K, Suzuki M, Ishikawa Y, et al. Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma. Radiat Oncol. 2014;9:1–7. https://doi.org/10.1186/1748-717X-9-26.

    Article  Google Scholar 

  20. Ohkawa A, Mizumoto M, Ishikawa H, Abei M, Fukuda K, Hashimoto T, et al. Proton beam therapy for unresectable intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol. 2015;30:957–63.

    Article  Google Scholar 

  21. Ohri N, Tome WA, Mendez Romero A, et al. Local control after stereotactic body radiation therapy for liver tumors. Int J Radiat Oncol Biol Phys. 2018.

  22. Colbert LE, Cloyd JM, Koay EJ, Crane CH, Vauthey JN. Proton beam radiation as salvage therapy for bilateral colorectal liver metastases not amenable to second-stage hepatectomy. Surgery. 2017;161:1543–8.

    Article  Google Scholar 

  23. Fukumitsu N, Okumura T, Takizawa D, Makishima H, Numajiri H, Murofushi K, et al. Proton beam therapy for metastatic liver tumors. Radiother Oncol. 2015;117:322–7.

    Article  Google Scholar 

  24. Fukumitsu N, Okumura T, Takizawa D, Numajiri H, Ohnishi K, Mizumoto M, et al. Proton beam therapy for liver metastases from gastric cancer. J Radiat Res. 2017;58:357–62.

    Article  Google Scholar 

  25. Fukumitsu N, Okumura T, Numajiri H, Takizawa D, Ohnishi K, Mizumoto M, et al. Follow-up study of liver metastasis from breast cancer treated by proton beam therapy. Mol Clin Oncol. 2017;7(1):56–60. https://doi.org/10.3892/mco.2017.1283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. •• Hong T, Wo J, Borger D, Yeap B, McDonnell E, et al. Phase II study of proton-based stereotactic body radiation therapy for liver metastases: importance of tumor genotype. JNCI: Journal of the National Cancer Institute. 2017;109(9):djx031. https://doi.org/10.1093/jnci/djx031. This is the largest prospective proton SBRT for liver metastases showing that the technique is safe and effective, even in large tumors.

  27. Kang JI, Sufficool DC, Hsueh CT, et al. A phase I trial of proton stereotactic body radiation therapy for liver metastases. J Gastrointest Oncol. 2019;10(1):112–7. https://doi.org/10.21037/jgo.2018.08.17.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Oshiro Y, Mizumoto M, Okumura T, Fukuda K, Fukumitsu N, Abei M. Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma. Radiother Oncol. 2017;123(2):240–5.

    Article  Google Scholar 

  29. McDuff SGR, Remillard KA, Zheng H. Liver reirradiation for patients with hepatocellular carcinoma and liver metastasis. Pract Radiat Oncol. 2018;8:414–21.

    Article  Google Scholar 

  30. Paganetti H. Range uncertainties in proton therapy and the role of Monte Carlo simulations. Phys Med Biol. 2012;57:R99–117.

    Article  CAS  Google Scholar 

  31. McGowan SE, Burnet NG, Lomax AJ. Treatment planning optimisation in proton therapy. Br J Radiol. 2013;86:20120288.

    Article  CAS  Google Scholar 

  32. Pfeiler T, Ahmad Khalil D, Ayadi M, et al. Motion effects in proton treatments of hepatocellular carcinoma-4d robustly optimised pencil beam scanning plans versus double scattering plans. Phys Med Biol. 2018;63:235006.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD, 21201, USA

    Osman Siddiqui, Ariel Pollock & Santanu Samanta

  2. Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD, 21201, USA

    Adeel Kaiser & Jason K. Molitoris

Authors
  1. Osman Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ariel Pollock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Santanu Samanta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adeel Kaiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jason K. Molitoris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason K. Molitoris.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Gastrointestinal Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Siddiqui, O., Pollock, A., Samanta, S. et al. Proton Beam Therapy in Liver Malignancies. Curr Oncol Rep 22, 30 (2020). https://doi.org/10.1007/s11912-020-0889-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-020-0889-9

Keywords

Search

Navigation