Monte Carlo study of the free radical yields in minibeam radiation therapy.

BACKGROUND: Minibeam radiation therapy (MBRT) is a novel technique which has been shown to widen the therapeutic window through significant normal tissue sparing. Despite the heterogeneous dose distributions, tumor control is still ensured. Nevertheless the exact radiobiological mechanisms responsible for MBRT efficacy are not fully understood. PURPOSE: Reactive oxygen species (ROS) resulting from water radiolysis were investigated given their implications not only on targeted DNA damage, but also for their role in the immune response and non-targeted cell signalling effects: two potential drivers of MBRT efficacy. METHODS: Monte Carlo simulations were performed using TOPAS-nBio to carry out the irradiation of a water phantom with beams of protons (pMBRT), photons (xMBRT), 4 He ions (HeMBRT), and 12 C ions (CMBRT). Primary yields at the end of the chemical stage were calculated in spheres of 20 µm diameter, located in the peaks and valleys at various depths up to the Bragg peak. The chemical stage was limited to 1 ns to approximate biological scavenging, and the yield of · OH, H2 O2 , and e aq - ${\rm e}^{-}_{\rm aq}$ was recorded. RESULTS: Beyond 10 mm, there were no substantial differences in the primary yields between peaks and valleys of the pMBRT and HeMBRT modalities. For xMBRT, there was a lower primary yield of the radical species · OH and e aq - ${\rm e}^{-}_{\rm aq}$ at all depths in the valleys compared to the peaks, and a higher primary yield of H2 O2 . Compared to the peaks, the valleys of the CMBRT modality were subject to a higher · OH and e aq - ${\rm e}^{-}_{\rm aq}$ yield, and lower H2 O2 yield. This difference between peaks and valleys became more severe in depth. Near the Bragg peak, the increase in the primary yield of the valleys over the peaks was 6% and 4% for · OH and e aq - ${\rm e}^{-}_{\rm aq}$ respectively, while there was a decrease in the yield of H2 O2 by 16%. Given the similar ROS primary yields in the peaks and valleys of pMBRT and HeMBRT, the level of indirect DNA damage is expected to be directly proportional to the peak to valley dose ratio (PVDR). The difference in the primary yields implicates a lower level of indirect DNA damage in the valleys compared to the peaks than what would be suggested by the PVDR for xMBRT, and a higher level for CMBRT. CONCLUSIONS: These results highlight the notion that depending on the particle chosen, one can expect different levels of ROS in the peaks and valley that goes beyond what would be expected by the macroscopic PVDR. The combination of MBRT with heavier ions is shown to be particularly interesting as the primary yield in the valleys progressively diverges from the level observed in the peaks as the LET increases. While differences in the reported · OH yields of this work implicated the indirect DNA damage, H2 O2 yields particularly implicate non-targeted cell signalling effects, and therefore this work provides a point of reference for future simulations in which the distribution of this species at more biologically relevant timescales could be investigated.

Dosimetry and radioprotection evaluations of very high energy electron beams.

Very high energy electrons (VHEEs) represent a promising alternative for the treatment of deep-seated tumors over conventional radiotherapy (RT), owing to their favourable dosimetric characteristics. Given the high energy of the electrons, one of the concerns has been the production of photoneutrons. In this article we explore the consequence, in terms of neutron yield in a water phantom, of using a typical electron applicator in conjunction with a 2 GeV and 200 MeV VHEE beam. Additionally, we evaluate the resulting ambient neutron dose equivalent at various locations between the phantom and a concrete wall. Through Monte Carlo (MC) simulations it was found that an applicator acts to reduce the depth of the dose build-up region, giving rise to lower exit doses but higher entrance doses. Furthermore, neutrons are injected into the entrance region of the phantom. The highest dose equivalent found was approximately 1.7 mSv/Gy in the vicinity of the concrete wall. Nevertheless, we concluded that configurations of VHEEs studied in this article are similar to conventional proton therapy treatments in terms of their neutron yield and ambient dose equivalent. Therefore, a clinical implementation of VHEEs would likely not warrant additional radioprotection safeguards compared to conventional RT treatments.

First theoretical determination of relative biological effectiveness of very high energy electrons.

Very high energy electrons (VHEEs, E > 70 MeV) present promising clinical advantages over conventional beams due to their increased range, improved penumbra and relative insensitivity to tissue heterogeneities. They have recently garnered additional interest in their application to spatially fractionated radiotherapy or ultra-high dose rate (FLASH) therapy. However, the lack of radiobiological data limits their rapid development. This study aims to provide numerical biologically-relevant information by characterizing VHEE beams (100 and 300 MeV) against better-known beams (clinical energy electrons, photons, protons, carbon and neon ions). Their macro- and microdosimetric properties were compared, using the dose-averaged linear energy transfer ([Formula: see text]) as the macroscopic metric, and the dose-mean lineal energy [Formula: see text] and the dose-weighted lineal energy distribution, yd(y), as microscopic metrics. Finally, the modified microdosimetric kinetic model was used to calculate the respective cell survival curves and the theoretical RBE. From the macrodosimetric point of view, VHEEs presented a potential improved biological efficacy over clinical photon/electron beams due to their increased [Formula: see text]. The microdosimetric data, however, suggests no increased biological efficacy of VHEEs over clinical electron beams, resulting in RBE values of approximately 1, giving confidence to their clinical implementation. This study represents a first step to complement further radiobiological experiments.