Minibeam radiation therapy: a micro- and nano-dosimetry Monte Carlo study
Résumé
Purpose: Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose
delivery method that is administered using a series of narrow (submillimetric) parallel beams. To
shed light on the biological effects of MBRT irradiation, we explored the micro- and nanodosimetric
characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte
Carlo (MC) calculations.
Methods: Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of
69 keV) minibeams were simulated using Geant4 MC code and the Geant4-DNA extension, which
allows the simulation of energy transfer points with nanometric accuracy. As the target of the
simulations, cells containing spherical nuclei with or without a detailed description of the DNA
(deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a
water phantom. The energy deposition and number of events in the cell nuclei were recorded in the
microdosimetry study, and the number of DNA breaks and their complexity were determined in the
nanodosimetric study, where a multi-scale simulation approach was used for the latter. For DNA
damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon
MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we consid-
ered the treatmen t of a brain tumor located at a depth of 75 mm.
Results: Both mean energy deposition at micrometric scale and DNA damage in the “valley” cell
nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT
and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged
minibeams were favorable for tumor control by producing similar effects in peak and valley cells after
70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of
proton beams for tumor control, as more aggressive events could be expected at the end of their
tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks,
although the majority of damage (>93%) was composed of isolated single strand breaks. The
pMBRT led to a significant increase in the proportion of clustered single strand breaks and double-
strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in
contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained con-
stant, irrespective of the depth and region (peak or valley).
Conclusions: Enhanced normal tissue sparing can be expected with these three MBRT techniques.
Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted
in a higher number of complex DNA damage clusters in the tumor region. The se results can aid
understanding of the biological mechanisms of MBRT.
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