Proton irradiation of plastic scintillator bars for POLAR-2.

POLAR-2, a plastic scintillator based Compton polarimeter, is currently under development and planned for a launch to the China Space Station in 2025. It is intended to shed a new light on our understanding of Gamma-Ray Bursts by performing high precision polarization measurements of their prompt emission. The instrument will be orbiting at an average altitude of 383 km with an inclination of 42° and will be subject to background radiation from cosmic rays and solar events.

Application of LiMgPO4 crystal for proton beam quality control in radiotherapy.

The radioluminescence (RL) emitted by LiMgPO4 detector under proton beam irradiation was investigated in real time at the radiotherapy facility in the Institute of Nuclear Physics Polish Academy of Sciences in Krakow. The facility uses protons accelerated by the AIC-144 isochronous cyclotron up to the energy of 60 MeV. The measurements of RL were carried out using a remote optical fiber device with a luminophore detector and photomultiplier located at opposite ends of the optical fiber.

Alanine/EPR dosimetry for mailed intercomparison at ocular proton therapy facilities-preliminary results for three centres for irradaitions at CCB IFJ PAN eyeline.

Quality control of therapeutic photon beams in the form of postal dose audits based on passive dosemeters is widely used in photon radiotherapy. On the other hand, no standardised dosimetry audit programme for proton centres has been established in Europe so far. We evaluated alanine/EPR dosimetry systems developed at the Istituto Superiore di Sanità (Italy), the Hasselt Universiteit (Belgium) and the Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences (Poland) for their applicability as a potential tool for routine mailed dose audits of passively scattered therapeutic proton beams.

Murine Breast Cancer Radiosensitization Using Oxygen Microbubbles and Metformin: Vessels Are the Key.

Radiotherapy is a cornerstone of cancer treatment, but tumor hypoxia and resistance to radiation remain significant challenges. Vascular normalization has emerged as a strategy to improve oxygenation and enhance therapeutic outcomes. In this study, we examine the radiosensitization potential of vascular normalization using metformin, a widely used anti-diabetic drug, and oxygen microbubbles (OMBs).

Proton irradiation of SiPM arrays for POLAR-2.

POLAR-2 is a space-borne polarimeter, built to investigate the polarization of Gamma-Ray Bursts and help elucidate their mechanisms. The instrument is targeted for launch in 2024 or 2025 aboard the China Space Station and is being developed by a collaboration between institutes from Switzerland, Germany, Poland and China. The instrument will orbit at altitudes between 340km and 450km with an inclination of and will be subjected to background radiation from cosmic rays and solar events.

Optically Stimulated Luminescent Response of the LiMgPO Silicone Foils to Protons and Its Dependence on Proton Energy.

Modern radiotherapy (RT) techniques, such as proton therapy, require more and more sophisticated dosimetry methods and materials. One of the newly developed technologies is based on flexible sheets made of a polymer, with the embedded optically stimulated luminescence (OSL) material in the form of powder (LiMgPO, LMP) and a self-developed optical imaging setup. The detector properties were evaluated to study its potential application in the proton treatment plan verification for eyeball cancer.

Ultrasound sensitive O microbubbles radiosensitize murine breast cancer but lead to higher metastatic spread.

The inadequate level of oxygenation in tumors has been shown to correlate not only with greater invasiveness of cancer cells, but also with a reduction in their sensitivity to anticancer therapies. Over the years, many attempts have been made to increase the oxygenation level of cancer, but most of them have been ineffective. We investigated the heterogeneous response of tumor tissue to phospholipid-coated oxygen microbubbles (OMB) in murine tumors in vivo using oxygen and hemoglobin saturation mapping and the influence of OMB treatment on microvasculature, perfusion, and radiotherapy effectiveness.

EURADOS REM-COUNTER INTERCOMPARISON AT MAASTRO PROTON THERAPY CENTRE: COMPARISON WITH LITERATURE DATA.

The Maastro Proton Therapy Centre is the first European facility housing the Mevion S250i Hyperscan synchrocyclotron. The proximity of the accelerator to the patient, the presence of an active pencil beam delivery system downstream of a passive energy degrader and the pulsed structure of the beam make the Mevion stray neutron field unique amongst proton therapy facilities. This paper reviews the results of a rem-counter intercomparison experiment promoted by the European Radiation Dosimetry Group at Maastro and compares them with those at other proton therapy facilities.

Joint EURADOS WG9-WG11 rem-counter intercomparison in a Mevion S250i proton therapy facility with Hyperscan pulsed synchrocyclotron.

Objective Proton therapy is gaining popularity because of the improved dose delivery over conventional radiation therapy. The secondary dose to healthy tissues is dominated by secondary neutrons. Commercial rem-counters are valuable instruments for the on-line assessment of neutron ambient dose equivalent (H*(10)).

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector.

. Treatment planning based on computer simulations wasproposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison.

3D Dosimetry Based on LiMgPO OSL Silicone Foils: Facilitating the Verification of Eye-Ball Cancer Proton Radiotherapy.

A direct verification of the three-dimensional (3D) proton clinical treatment plan prepared for tumor in the eyeball, using the Eclipse Ocular Proton Planning system (by Varian Medical Systems), has been presented. To achieve this, a prototype of the innovative two-dimensional (2D) circular silicone foils, made of a polymer with the embedded optically stimulated luminescence (OSL) material in powder form (LiMgPO), and a self-developed optical imaging system, consisting of an illuminating light source and a high-sensitive CCD camera has been applied. A specially designed lifelike eyeball phantom has been used, constructed from 40 flat sheet LMP-based silicone foils stacked and placed together behind a spherical phantom made by polystyrene, all to reflect the curvature of the real eyeball.

Proton scanning and X-ray beam irradiation induce distinct regulation of inflammatory cytokines in a preclinical mouse model.

Purpose: Conventional X-ray radiotherapy induces a pro-inflammatory response mediated by altered expression of inflammation-regulating cytokines. Proton scanning and X-ray irradiation produce distinct changes to cytokine gene expression in vitro suggesting that proton beam therapy may induce an inflammatory response dissimilar to that of X-ray radiation. The purpose of the present study was to determine whether proton scanning beam radiation and conventional X-ray photon radiation would induce differential regulation of circulating cytokines in vivo.

Modeling the radiation-induced cell death in a therapeutic proton beam using thermoluminescent detectors and radiation transport simulations.

Changes in the relative biological effectiveness (RBE) of the radiation-induced cell killing of human salivary glands (HSG) were assessed along the Bragg peak of a 60 MeV clinical proton beam by means of coupling biophysical models with the results of Monte Carlo radiation transport simulations and experimental measurements with luminescent detectors. The fluence- and dose-mean unrestricted proton LET were determined along the Bragg peak using a recently developed methodology based on the combination of the response of LiF:Mg,Ti (MTS-7) and LiF:Mg,Cu,P (MCP-7) thermoluminescent detectors. The experimentally assessed LET values were compared with the results of radiation transport simulations using the Monte Carlo code PHITS, showing a good agreement.

Increased elasticity of melanoma cells after low-LET proton beam due to actin cytoskeleton rearrangements.

Cellular response to non-lethal radiation stress include perturbations in DNA repair, angiogenesis, migration, and adhesion, among others. Low-LET proton beam radiation has been shown to induce somewhat different biological response than photon radiation. For example, we have shown that non-lethal doses of proton beam radiation inhibited migration of cells and that this effect persisted long-term.

Comparison of Coding Transcriptomes in Fibroblasts Irradiated With Low and High LET Proton Beams and Cobalt-60 Photons.

Purpose: To identify differential cellular responses after proton and photon irradiation by comparing transcriptomes of primary fibroblasts irradiated with either radiation type.

Methods And Materials: A panel of primary dermal fibroblast cultures was irradiated with low and higher linear energy transfer (LET) proton beams. Cobalt-60 photon irradiation was used as reference.

Biological effects and inter-individual variability in peripheral blood lymphocytes of healthy donors exposed to 60 MeV proton radiotherapeutic beam.

The aim of our study was to investigate the amount of initial DNA damage and cellular repair capacity of human peripheral blood lymphocytes exposed to the therapeutic proton beam and compare it to X-rays. Lymphocytes from 10 healthy donors were irradiated in the Spread Out Bragg Peak of the 60 MeV proton beam or, as a reference, exposed to 250 kV X-rays. DNA damage level was assessed using the alkaline version of the comet assay method.

Optimal reference genes for normalization of qPCR gene expression data from proton and photon irradiated dermal fibroblasts.

The transcriptional response of cells exposed to proton radiation is not equivalent to the response induced by traditional photon beams. Changes in cellular signalling is most commonly studied using the method Quantitative polymerase chain reaction (qPCR). Stable reference genes must be used to accurately quantify target transcript expression.

Calcitriol and Calcidiol Can Sensitize Melanoma Cells to Low⁻LET Proton Beam Irradiation.

Proton beam irradiation promises therapeutic utility in the management of uveal melanoma. Calcitriol (1,25(OH)₂D₃)-the biologically active metabolite of vitamin D₃-and its precursor, calcidiol (25(OH)D₃), exert pleiotropic effects on melanoma cells. The aim of the study was to evaluate the effect of both calcitriol and calcidiol on melanoma cell proliferation and their response to proton beam irradiation.

DOSIMETRIC CHARACTERIZATION OF COLLIMATORS FOR SPATIALLY FRACTIONATED PROTON THERAPY OF THE EYE.

The aim of these studies was to investigate depth dose distribution of a 60 MeV proton beam formed by a set of dedicated mesh-formed collimators. The set of mini-beams formed by the mesh is scattered in the tissue and lead to uniform energy deposition in the target volume. The rationale is to protect the eyelid skin from complications after hypofractionated radiation therapy.

Proton beam irradiation inhibits the migration of melanoma cells.

Purpose: In recent years experimental data have indicated that low-energy proton beam radiation might induce a difference in cellular migration in comparison to photons. We therefore set out to compare the effect of proton beam irradiation and X-rays on the survival and long-term migratory properties of two cell lines: uveal melanoma Mel270 and skin melanoma BLM.

Materials And Methods: Cells treated with either proton beam or X-rays were analyzed for their survival using clonogenic assay and MTT test.

Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation.

Introduction: Proton beam therapy delivers a more conformal dose distribution than conventional radiotherapy, thus improving normal tissue sparring. Increasing linear energy transfer (LET) along the proton track increases the relative biological effectiveness (RBE) near the distal edge of the Spread-out Bragg peak (SOBP). The severity of normal tissue side effects following photon beam radiotherapy vary considerably between patients.

Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo.

Introduction: The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP).

Method: The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off.

Chemically tuned linear energy transfer dependent quenching in a deformable, radiochromic 3D dosimeter.

Most solid-state detectors, including 3D dosimeters, show lower signal in the Bragg peak than expected, a process termed quenching. The purpose of this study was to investigate how variation in chemical composition of a recently developed radiochromic, silicone-based 3D dosimeter influences the observed quenching in proton beams. The dependency of dose response on linear energy transfer, as calculated through Monte Carlo simulations of the dosimeter, was investigated in 60 MeV proton beams.

Technical Note: Improving proton stopping power ratio determination for a deformable silicone-based 3D dosimeter using dual energy CT.

Purpose: The aim of this study was to investigate whether the stopping power ratio (SPR) of a deformable, silicone-based 3D dosimeter could be determined more accurately using dual energy (DE) CT compared to using conventional methods based on single energy (SE) CT. The use of SECT combined with the stoichiometric calibration method was therefore compared to DECT-based determination.

Methods: The SPR of the dosimeter was estimated based on its Hounsfield units (HUs) in both a SECT image and a DECT image set.

Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

Purpose: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs.

Methods And Materials: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow.

Results: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014.