BIOPHYSICAL SIMULATION TOOL PARTRAC: MODELLING PROTON BEAMS AT THERAPY-RELEVANT ENERGIES

2019 ◽  
Vol 186 (2-3) ◽  
pp. 172-175 ◽  
Author(s):  
Werner Friedland ◽  
Pavel Kundrát ◽  
Janine Becker ◽  
Markus Eidemüller

ABSTRACT The biophysical simulation tool PARTRAC has been primarily developed to model radiation physics, chemistry and biology on nanometre to micrometre scales. However, the tool can be applied in simulating radiation effects in an event-by-event manner over macroscopic volumes as well. Benchmark simulations are reported showing that PARTRAC does reproduce the macroscopic Bragg peaks of proton beams, although the penetration depths are underestimated by a few per cent for high-energy beams. PARTRAC also quantifies the increase in DNA damage and its complexity along the beam penetration depth. Enhanced biological effectiveness is predicted in particular within distal Bragg peak parts of therapeutic proton beams.

Author(s):  
А. Белоусов ◽  
A. Belousov ◽  
Р. Бахтиозин ◽  
R. Bahtiosin ◽  
М. Колыва­нова ◽  
...  

Purpose: Accurate establishing the value of relative biological effectiveness (RBE) for high energy protons is one of the main challenges of modern radiotherapy. The purpose of the study is to calculate the depth dependence of RBE for proton beams forming a spread-out Bragg peak. Material and methods: Spatial distributions of absorbed dose and dose-average linear energy transfer (LET) for 50-100 MeV (0.5 MeV energy step) monochromatic proton beams were obtained by Monte-Carlo computer simulation using Geant4 software. A linear dependence of RBE on the dose-average LET was used. Absorbed dose distributions were obtained in a water phantom for monochromatic pencil proton beams of 2.5 mm radius. The absorbed dose and the dose-average LET values were calculated in voxels with dimensions of 2×2×0.2 mm. Results: Calculations of depth dependencies of absorbed dose and dose-average LET for 50–100 MeV monochromatic proton beams were performed. Depth dependencies of RBE for these beams were established. The weighing coefficients values allowing to generate uniformspread-out Bragg peak (SOBP) were determined. Depth distribution of “RBE-weighted” dose and RBE values for SOBP were found. Conclusion: The impact of the initial beam energy step on the degree of homogeneity of the modified Bragg curve was investigated. It was shown that a step up to 1.5 MeV is acceptable for generate a smooth Bragg curve. The depth dependence of the average RBE value is a complex function, which rapidly changes especially at the far end of the SOBP. RBE may vary up to 10-30 % compared to current clinical value. The linear model of RBE-LET dependence shown in the study can be easily used in dosimetric planning systems, that may will significantly improve the quality of proton radiotherapy.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 946 ◽  
Author(s):  
Eirini Terpsi Vitti ◽  
Jason L Parsons

Proton beam therapy (PBT) offers significant benefit over conventional (photon) radiotherapy for the treatment of a number of different human cancers, largely due to the physical characteristics. In particular, the low entrance dose and maximum energy deposition in depth at a well-defined region, the Bragg peak, can spare irradiation of proximal healthy tissues and organs at risk when compared to conventional radiotherapy using high-energy photons. However, there are still biological uncertainties reflected in the relative biological effectiveness that varies along the track of the proton beam as a consequence of the increases in linear energy transfer (LET). Furthermore, the spectrum of DNA damage induced by protons, particularly the generation of complex DNA damage (CDD) at high-LET regions of the distal edge of the Bragg peak, and the specific DNA repair pathways dependent on their repair are not entirely understood. This knowledge is essential in understanding the biological impact of protons on tumor cells, and ultimately in devising optimal therapeutic strategies employing PBT for greater clinical impact and patient benefit. Here, we provide an up-to-date review on the radiobiological effects of PBT versus photon radiotherapy in cells, particularly in the context of DNA damage. We also review the DNA repair pathways that are essential in the cellular response to PBT, with a specific focus on the signaling and processing of CDD induced by high-LET protons.


2021 ◽  
Author(s):  
Fabiana Da Pieve ◽  
Bin Gu ◽  
Natalia Koval ◽  
Daniel Muñoz Santiburcio ◽  
Jos Teunissen ◽  
...  

<p>Cosmic Rays, in particular the high charge and high energy (HZE) particles and eventual secondary low energy protons, are high Linear Energy Transfer (LET) radiation, i.e. they transfer a high amount of energy to the target per unit path length travelled in the target itself, leaving behind a dense track of ionization and atomic excitations. Understanding the radiation physics and the biology induced by the impact of high LET radiation is of importance for different fields of research, such as radiation therapy with charged particles, space radiation protection of astronauts and of human explorers on Mars and eventually also survival of any bacterial, plant cell on other planetary/small bodies. While data for low LET radiation  such as X-ray have been studied in the survivors of the atomic-bombs, medical patients and nuclear reactor workers, for high LET radiation there is no relevant collection of human data for risk estimates, and experiments with nuclei created at accelerators are necessary.</p><p>At present we still do not have an understanding of how the  radiation  interaction  with a  single nanometric  target (units of DNA), the so-called track  structure [1],  should  decide  the  fate  of  the  irradiated cell. Monte Carlo (MC) track structure codes essentially work only with the physics given by impact cross sections on the sole water, there is no real consideration of the electronic/chemical characteristics of the hosted biomolecule [2]. Limitations given by such an approach have been highlighted [3], but on the positive side a massive effort is being done to follow the different steps of radiation effects up to biological damage [4].</p><p>In this contribution we would like to highlight how a chain of models from different communities could be of help to study the radiation effects on biomolecules. In particular, we will present how ab-initio (parameter-free) approaches from the chemical-physics community can be used to derive in detail the energy loss of the impacting ions/secondary electrons on water and small biological units [5,6], either following in real time the ion or based on perturbative theories for low energy electrons, and how the derived quantity can be given  as input to Monte Carlo track structure codes, extending their capabilities to different relevant targets. Given the physical limitations and high costs of irradiation experiments, such calculations offer an efficient approach that can boost the understanding of radiation physics and consolidate existing MC track structure codes.</p><p>This work is initiated in the context of the EU H2020 project ESC2RAD, Grant 776410.</p><p>[1] H. Nikjoo, S. Uehara, W.E. Wilson, et al, International Journal of Radiation Biology 73, 355 (1998)</p><p>[2] H. Palmans, H Rabus, A L Belchior, et al, Br. J. Radiol. 88, 20140392 (2015)</p><p>[3] H. Rabus and H. Nettelback, Radiation Measurements 46, 1522 (2011)</p><p>[4] M. Karamitros, S. Luan, M.A. Bernal, et al,  Journal of Computational Physics 274,  841 (2014)</p><p>[5] B. Gu, B. Cunningham D. Munoz-Santiburcio, F. Da Pieve, E. Artacho and J. Kohanoff, J. Chem. Phys. 153, 034113 (2020)</p><p>[6] N. Koval, J. Kohanoff, E. Artacho et al, in preparation</p>


2022 ◽  
Vol 23 (2) ◽  
pp. 878
Author(s):  
Laura C. Paterson ◽  
Amy Festarini ◽  
Marilyne Stuart ◽  
Fawaz Ali ◽  
Christie Costello ◽  
...  

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.


2021 ◽  
Vol 11 (24) ◽  
pp. 11986
Author(s):  
Valerio Ricciardi ◽  
Pavel Bláha ◽  
Raffaele Buompane ◽  
Giuseppina Crescente ◽  
Giacomo Cuttone ◽  
...  

Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.


2021 ◽  
Vol 11 ◽  
Author(s):  
Pavel Bláha ◽  
Chiara Feoli ◽  
Stefano Agosteo ◽  
Marco Calvaruso ◽  
Francesco Paolo Cammarata ◽  
...  

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.


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