Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

Abstract

Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects related to the ion-medium interactions on a nanometre scale. We demonstrate that the phenomenon-based MultiScale Approach to the assessment of radiation damage with ions gives a positive answer to this question. We apply this approach to numerous experiments where survival curves were obtained for different cell lines and conditions. Contrary to other, in essence empirical methods for evaluation of macroscopic effects of ionising radiation, the MultiScale Approach predicts the biodamage based on the physical effects related to ionisation of the medium, transport of secondary particles, chemical interactions, thermo-mechanical pathways of biodamage, and heuristic biological criteria for cell survival. We anticipate this method to give great impetus to the practical improvement of ion-beam cancer therapy and the development of more efficient treatment protocols.

Ion-impact-induced multifragmentation of liquid droplets

“…A series of works [14,21,22] showed that propagation of reactive species by the collective flow intrinsic to shock waves significantly affects cell damage by enlarging the volume exposed to these species and not allowing them to annihilate in dense regions adjacent to ions' paths. Cell survival probabilities measured in different conditions successfully compare with those calculated with the shock wave scenario in place [23]. The most recent work [24] is relating the change in cell survival probability along the spread-out Bragg peak with a uniform physical dose profile to the shock wave effect.…”

Radial doses around energetic ion tracks and the onset of shock waves on the nanoscale

“…2.1). This more sophisticated approach is capable of describing the main effects produced by these numerous electrons in the MSA [5,9,15]. In addition the δ-electrons, much less frequent, will be included here by a simpler methodology based on a spatially restricted LET formula [22] (Sect.…”

“…The MSA is a phenomenon-based largely analytical method that is aimed at understanding the radiation damage with ions on a quantitative level. Its predictive power was recently demonstrated by the comparison of calculated cell survival probabilities for different doses, LET, oxygen concentrations and DNA repair efficiency levels with those obtained experimentally [5,15,16]. The role of shock waves was included in these calculations.…”

Radiation dose–response curves: cell repair mechanisms vs. ion track overlapping

“…Interesting exceptions are fast protons for which the LET value is more than twice so high as for gamma rays but the α parameter is smaller. In the past, this finding led to speculation that the ionization density induced by protons should be smaller than that suggested by the ion-track model and the energy deposition could take place at larger distances due to electron wake waves or diffusion effects [8,9,13].…”

“…Some comprehensive models -for example the multiscale approach [8,9] implement some additional effects and corresponding parameters describing biological as well as chemical and thermo-mechanical processes like the influence of oxygen enhancement ratio and free radicals propagation via shock waves. Other, more phenomenological models simply compare effects of different radiation quality assuming the ionization density as the most significant parameter describing the biological effects.…”