Radiobiological issues in prospective carbon ion therapy trials

Piero Fossati, Naruhiro Matsufuji, Tadashi Kamada, Christian P. Karger*

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

54 Citations (Scopus)


Carbon ion radiotherapy (CIRT) is developing toward a versatile tool in radiotherapy; however, the increased relative biological effectiveness (RBE) of carbon ions in tumors and normal tissues with respect to photon irradiation has to be considered by mathematical models in treatment planning. As a consequence, dose prescription and definition of dose constraints are performed in terms of RBE weighted rather than absorbed dose. The RBE is a complex quantity, which depends on physical variables, such as dose and beam quality as well as on normal tissue- or tumor-specific factors. At present, three RBE models are employed in CIRT: (a) the mixed-beam model, (b) the Microdosimetric Kinetic Model (MKM), and (c) the local effect model. While the LEM is used in Europe, the other two models are employed in Japan, and unfortunately, the concepts of how the nominal RBE-weighted dose is determined and prescribed differ significantly between the European and Japanese centers complicating the comparison, transfer, and reproduction of clinical results. This has severe impact on the way treatments should be prescribed, recorded, and reported. This contribution reviews the concept of the clinical application of the different RBE models and the ongoing clinical CIRT trials in Japan and Europe. Limitations of the RBE models and the resulting radiobiological issues in clinical CIRT trials are discussed in the context of current clinical evidence and future challenges.

Original languageEnglish
Pages (from-to)e1096-e1110
JournalMedical Physics
Issue number11
Publication statusPublished - Nov 2018
Externally publishedYes


  • carbon ion therapy
  • clinical trials
  • dose prescription
  • radiobiology
  • RBE modeling
  • relative biological effectiveness (RBE)
  • Radiobiology
  • Humans
  • Clinical Trials as Topic
  • Relative Biological Effectiveness
  • Heavy Ion Radiotherapy/methods

ASJC Scopus subject areas

  • Biophysics
  • Radiology, Nuclear Medicine and Imaging


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