Monte Carlo implementation of new algorithms for the evaluation of averaged-dose and -track linear energy transfers in 62 MeV clinical proton beams

Petringa, Giada; Pandola, L.; Agosteo, S.; Catalano, Roberto; Colautti, P.; Conte, V.; Cuttone, G.; Fan, Kang‐Hsing; Mei, Zhenyu; Rosenfeld, Anatoly B.; Selva, A. Della; Cirrone, G.A.P.

doi:10.1088/1361-6560/abaeb9

Cited by 21 publications

(18 citation statements)

References 30 publications

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“…The CATANA beamline was entirely simulated using the Hadrontherapy Geant4 advanced example ( 24 , 25 ). The averaged LET-dose total and LET-dose primary were then calculated according to the procedure reported in ( 26 ). Microdosimetric spectra were measured with three detectors: mini-TEPC ( 27 ), Silicon telescope ( 28 ) and MicroPlus probe ( 29 ), and the dose mean lineal energy y D was derived as the ratio between the mean energy imparted and the mean track length of primary protons in the irradiated sensitive volumes.…”

Section: Methodsmentioning

confidence: 99%

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

et al. 2021

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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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Section: Methodsmentioning

confidence: 99%

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

et al. 2021

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“…The measured dose distribution as well as the LET and dose simulated by using the Geant4 Hadrontherapy advanced example that reproduce the entire beamline [28], is reported in Figure 1). The algorithms adopted to compute the LET take into account both primary and secondary particles interacting in a voxel, more details are reported in [27].…”

Section: Experimental Set-upmentioning

confidence: 99%

“…Cell sample irradiations were carried out positioning each flask at 24 mm, the mid-position of the spread-out Bragg peak, to mimic a clinical condition, with dose values ranging from 1 to 4 Gy and a dose rate of 6 Gy min −1 . Finally, the microdosimetric spectra were acquired positioning the mini-TEPC and MicroPlus-Bridge detectors at the entrance and mid position along the same SOBP, while the depths were varied by placing a stack of calibrated PMMA layers between the detectors and the beam collimator [27]. The mini-TEPC is a miniaturized, tissue-equivalent, proportional counter developed at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL) to work in a sealed mode, without gas flow [25].…”

Section: Experimental Set-upmentioning

confidence: 99%

“…Microdosimetry experimental spectra acquired to estimate the proton LET in different positions along the SOBP, were measured in the same experimental conditions of the biological sample irradiation. Two different detectors were used to this scope: a mini-TEPC [24,25], developed at the Legnaro National Laboratories of the National Institute for Nuclear Physics (LNL-INFN) and a Silicon On Insulator (SOI) microdosimeter with 3D Sensitive Volumes (MicroPlus-Bridge) [26,27]. The Loncol's weighting function was then applied to assess the microdosimetric RBE and compare it with the experimental one.…”

Section: Introductionmentioning

confidence: 99%

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Radiobiological Outcomes, Microdosimetric Evaluations and Monte Carlo Predictions in Eye Proton Therapy

et al. 2021

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CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) was the first Italian protontherapy facility dedicated to the treatment of ocular neoplastic pathologies. It is in operation at the LNS Laboratories of the Italian Institute for Nuclear Physics (INFN-LNS) and to date, 500 patients have been successfully treated. Even though proton therapy has demonstrated success in clinical settings, there is still a need for more accurate models because they are crucial for the estimation of clinically relevant RBE values. Since RBE can vary depending on several physical and biological parameters, there is a clear need for more experimental data to generate predictions. Establishing a database of cell survival experiments is therefore useful to accurately predict the effects of irradiations on both cancerous and normal tissue. The main aim of this work was to compare RBE values obtained from in-vitro experimental data with predictions made by the LEM II (Local Effect Model), Monte Carlo approaches, and semi-empirical models based on LET experimental measurements. For this purpose, the 92.1 uveal melanoma and ARPE-19 cells derived from normal retinal pigmented epithelium were selected and irradiated in the middle of clinical SOBP of the CATANA proton therapy facility. The remarkable results show the potentiality of using microdosimetric spectrum, Monte Carlo simulations and LEM model to predict not only the RBE but also the survival curves.

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“…The CATANA beamline was simulated using the Gean-t4 advanced example, "HADRONTHERAPY", an application specifically developed to simulate a typical eye proton-therapy beamline. The possibility to calculate the averaged total LET-track and total LET-dose as a function of the penetration depth in water was recently improved and updated 43 with respect to the implementation reported in Ref. [44].…”

Section: D Geant4 Simulationsmentioning

confidence: 99%

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter

et al. 2020

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Purpose The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62 MeV ocular therapy proton beams. Methods A novel diamond microdosimeter with a well‐defined sensitive volume was fabricated and tested with a monoenergetic and spread‐out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar‐sectional area of 100 µm × 100 µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy (y¯F), dose mean lineal energy (y¯D) as well as microdosimetric relative biological effectiveness (RBEµ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. Results The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile‐up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1 keV/μm. The y¯F and y¯D values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. Conclusions The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.

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Monte Carlo implementation of new algorithms for the evaluation of averaged-dose and -track linear energy transfers in 62 MeV clinical proton beams

Cited by 21 publications

References 30 publications

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

Radiobiological Outcomes, Microdosimetric Evaluations and Monte Carlo Predictions in Eye Proton Therapy

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62 MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter

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