Particle Therapy for metastatic liver tumors: evaluation of clinical differences between proton and carbon ion therapies

Reviewer: Curtiland Deville
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 28, 2010

Presenter: Kazuki Terashima
Presenter's Affiliation: Hyogo Ion Beam Medical Center, Department of Radiology, Tatsuno, Japan


  • The liver is inherently sensitive to radiation therapy, thus limiting the use of external beam photon therapy in treating primary tumors and isolated metastases.
  • The unique physical properties of proton and heavy ion particles - allowing for increased deposition of dose within the target while sparing adjacent normal tissues - have led to increased application of particle therapy in liver tumors.
  • The radiobiologic advantages of carbon ion therapy, including increased LET and RBE, may provide further benefit in controlling tumors within the liver.
  • The purpose of this study was to evaluate the clinical differences between proton and carbon ion therapies for metastatic liver tumors.


  • The study included 47 patients with 51 metastatic liver lesions treated between January 2003 and January 2009.
  • Primary tumors were majority colorectal (26), as well as gastric (5), and other (17).
  • Tumor size ranged from 0.8 cm to 8.0 cm, with a median size of 3.1 cm.
  • 24 patients received proton therapy and 27 patients received carbon ion therapy
  • All patients received 56-68 Gy(RBE) in 8 fractions.
  • Overall survival, recurrence-free survival, distant metastasis, and local control rates were evaluated with Kaplan-Meier curves.
  • Acute and late morbidities were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.


  • Median follow-up was 19.1 months, ranging from 4.1 – 58.7 months.
  • 1, 2, and 3 year overall survival rates did not differ significantly and were respectively for proton therapy 81.8%, 47.3%, and 13.5%, and for carbon ion therapy, 87.8%, 70% and 60% (p = 0.13)
  • There were similarly no differences in 1-year recurrence free survival rates.
  •  1 and 2 year local control rates 78.9% and 65.7% in the proton group and 64.5% and 42.2% in the carbon group (p=0.51)
  • Only one grade 3 acute reaction was observed - an acute elevation in transaminases
  • A single grade 4 late toxicity was recorded, radiation dermatitis.

Author's Conclusions

  • There were no statistically significant differences in clinical outcomes between proton and carbon ion therapy in this retrospective analysis.
  • Randomized controlled trials are planned to confirm these findings.

Scientific Implications

  • The treatment of oligometastatic disease is an ever-expanding field and of particular interest in the setting of isolated liver metastasis.
  • The potential application of the physical and biologic properties of particle therapy with successful clinical outcome is therefore of continued future importance.
  • This study is limited by its relatively small number of patients and retrospective, nonrandomized nature. A prospective randomized trial which the author's express an intention to pursue, if completed, should further clarify whether the increased LET and RBE of carbon ion therapy translates to a clinical benefit in the treatment of primary or metastatic liver tumors.