Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model

Int J Mol Sci. 2021 Oct 8;22(19):10877. doi: 10.3390/ijms221910877.


Chromosome aberrations are widely considered among the best biomarkers of radiation health risk due to their relationship with late cancer incidence. In particular, aberrations in peripheral blood lymphocytes (PBL) can be regarded as indicators of hematologic toxicity, which is a major limiting factor of radiotherapy total dose. In this framework, a radiobiological database describing the induction of PBL dicentrics as a function of ion type and energy was developed by means of the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model, which has been previously applied to predict the effectiveness of therapeutic-like ion beams at killing tumour cells. This database was then read by the FLUKA Monte Carlo transport code, thus allowing us to calculate the Relative Biological Effectiveness (RBE) for dicentric induction along therapeutic C-ion beams. A comparison with previous results showed that, while in the higher-dose regions (e.g., the Spread-Out Bragg Peak, SOBP), the RBE for dicentrics was lower than that for cell survival. In the lower-dose regions (e.g., the fragmentation tail), the opposite trend was observed. This work suggests that, at least for some irradiation scenarios, calculating the biological effectiveness of a hadrontherapy beam solely based on the RBE for cell survival may lead to an underestimation of the risk of (late) damage to healthy tissues. More generally, following this work, BIANCA has gained the capability of providing RBE predictions not only for cell killing, but also for healthy tissue damage.

Keywords: Monte Carlo; biomarkers; biophysical modelling; cancer; cell death; chromosome aberrations; hadrontherapy; healthy tissue damage; peripheral blood lymphocytes; relative biological effectiveness.

MeSH terms

  • Biophysics
  • Cell Death*
  • Chromosome Aberrations / radiation effects*
  • Heavy Ion Radiotherapy / adverse effects*
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / pathology*
  • Monte Carlo Method*
  • Neoplasms / radiotherapy*
  • Relative Biological Effectiveness*