Investigating ultra-high dose rate water radiolysis using the Geant4-DNA toolkit and a Geant4 model of the Oriatron eRT6 electron linac.

Ultra-high dose rate FLASH radiotherapy, a promising cancer treatment approach, offers the potential to reduce healthy tissue damage during radiotherapy. As the mechanisms underlying this process remain unknown, several hypotheses have been proposed, including the altered production of radio-induced species under ultra-high dose rate (UHDR) conditions. This study explores realistic irradiation scenarios with various dose-per-pulse and investigates the role of pulse temporal structure.

Metrology for advanced radiotherapy using particle beams with ultra-high dose rates.

Dosimetry of ultra-high dose rate beams is one of the critical components which is required for safe implementation of FLASH radiotherapy (RT) into clinical practice. In the past years several national and international programmes have emerged with the aim to address some of the needs that are required for translation of this modality to clinics. These involve the establishment of dosimetry standards as well as the validation of protocols and dosimetry procedures.

Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

Purpose: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom.

Methods And Materials: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.

Acute Hypoxia Does Not Alter Tumor Sensitivity to FLASH Radiation Therapy.

Purpose: Tumor hypoxia is a major cause of treatment resistance, especially to radiation therapy at conventional dose rate (CONV), and we wanted to assess whether hypoxia does alter tumor sensitivity to FLASH.

Methods And Materials: We engrafted several tumor types (glioblastoma [GBM], head and neck cancer, and lung adenocarcinoma) subcutaneously in mice to provide a reliable and rigorous way to modulate oxygen supply via vascular clamping or carbogen breathing. We irradiated tumors using a single 20-Gy fraction at either CONV or FLASH, measured oxygen tension, monitored tumor growth, and sampled tumors for bulk RNAseq and pimonidazole analysis.

More May Not be Better: Enhanced Spacecraft Shielding May Exacerbate Cognitive Decrements by Increasing Pion Exposures during Deep Space Exploration.

The pervasiveness of deep space radiation remains a confounding factor for the transit of humans through our solar system. Spacecraft shielding both protects astronauts but also contributes to absorbed dose through galactic cosmic ray interactions that produce secondary particles. The resultant biological effects drop to a minimum for aluminum shielding around 20 g/cm2 but increase with additional shielding.

Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional audit of dosimetric variability between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene ($~1.

Measurement of the Tm beta spectrum.

The beta spectrum of the main transition of the β decay of Tm was measured using a double focalizing spectrometer. The instrument was lately improved in order to reduce its low energy threshold to 34 keV. We used the spectrometer to measure the beta spectrum end-point energy of the main transition of Tm decay using the Kurie plot formalism.

Activity standardisation of Si at IRA-METAS.

This work explores the primary activity standardisation of Si as part of the SINCHRON project that aims at filling the geochronological dating gap by making a new precise measurement of the half-life of this nuclide. The stability of some of the radioactive test solutions, providing Si as hexafluorosilicic acid (HSiF), was monitored over long periods, pointing to the adequate sample composition and vial type to ensure stability. These solutions were standardised using liquid scintillation counting with the triple to double coincidence ratio (TDCR) technique and the CIEMAT-NIST efficiency tracing (CNET) method.

Activity standardisation of Lu.

Lu decays through low-energy β- and γ-emissions in addition to conversion and Auger electrons. To support the use of this radiopharmaceutical in Switzerland, a Lu solution was standardised using the β-γ coincidence technique, as well as the TDCR method. The solution had no Lu impurity.

Construction and dosimetric characterization of a motorized scanning-slit system for electron FLASH experiments.

Background: Beam scanning is a useful technique for the treatment of large tumors when the primary beam size is limited, which is the case with radiation beams used in FLASH radiotherapy.

Purpose: To optimize beam scanning as a dose delivery method for FLASH radiotherapy, it is necessary to first understand the effects of beam scanning on the FLASH effect. To do so, biological FLASH experiments need to be done using defined beam parameters with beam scanning and compared to the situation without beam scanning.

Effect of Conventional and Ultrahigh Dose Rate FLASH Irradiations on Preclinical Tumor Models: A Systematic Analysis.

Purpose: Compared with conventional dose rate irradiation (CONV), ultrahigh dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed "FLASH effect," also depends on the tumor toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study examined the hypothesis of tumor isoefficacy for UHDR versus CONV and aimed to identify potential knowledge gaps to inspire future in vivo studies.

The general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension to investigate mechanisms underlying the FLASH effect in radiotherapy: Current status and challenges.

FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown.

Independent Reproduction of the FLASH Effect on the Gastrointestinal Tract: A Multi-Institutional Comparative Study.

FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV).

Modeling of scavenging systems in water radiolysis with Geant4-DNA.

Purpose: This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of HO following a Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons.

Methods: To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers.

Activity Measurement of Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics.

Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE), Sc is produced by enriched CaO-target irradiation with a cyclotron.

Elucidating the neurological mechanism of the FLASH effect in juvenile mice exposed to hypofractionated radiotherapy.

Background: Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional dose-rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to a human pediatric medulloblastoma brain tumor, we used a radiosensitive juvenile mouse model to assess adverse long-term neurological outcomes.

Methods: Cohorts of 3-week-old male and female C57Bl/6 mice exposed to hypofractionated (2 × 10 Gy, FLASH-RT or CONV-RT) whole brain irradiation and unirradiated controls underwent behavioral testing to ascertain cognitive status four months posttreatment.

Half-life measurement of Sc and Sc.

The half-lives of Sc and Sc were measured by following their decay rate using several measurement systems: two ionization chambers and three γ-spectrometry detectors with digital and/or analogue electronics. For Sc, the result was the combination of seven half-life values giving a result of 4.042(7) h, which agrees with the last reported value of 4.

Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies.

Background And Purpose: We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates.

The minimal FLASH sparing effect needed to compensate the increase of radiobiological damage due to hypofractionation for late-reacting tissues.

Purpose: Normal tissue (NT) sparing by ultra-high dose rate (UHDR) irradiations compared to conventional dose rate (CONV) irradiations while being isotoxic to the tumor has been termed "FLASH effect" and has been observed when large doses per fraction (d ≳ 5 Gy) have been delivered. Since hypofractionated treatment schedules are known to increase toxicities of late-reacting tissues compared to normofractionated schedules for many clinical scenarios at CONV dose rates, we developed a formalism based on the biologically effective dose (BED) to assess the minimum magnitude of the FLASH effect needed to compensate the loss of late-reacting NT sparing when reducing the number of fractions compared to a normofractionated CONV treatment schedule while remaining isoeffective to the tumor.

Methods: By requiring the same BED for the tumor, we derived the "break-even NT sparing weighting factor" W for the linear-quadratic (LQ) and LQ-linear (LQ-L) models for an NT region irradiated at a relative dose r (relative to the prescribed dose per fraction d to the tumor).

Normal Tissue Sparing by FLASH as a Function of Single-Fraction Dose: A Quantitative Analysis.

Purpose: The FLASH effect designates normal tissue sparing by ultra-high dose rate (UHDR) compared with conventional dose rate irradiation without compromising tumor control. Understanding the magnitude of this effect and its dependency on dose are essential requirements for an optimized clinical translation of FLASH radiation therapy. In this context, we evaluated available experimental data on the magnitudes of normal tissue sparing provided by the FLASH effect as a function of dose, and followed a phenomenological data-driven approach for its parameterization.

Determination of the ion collection efficiency of the Razor Nano Chamber for ultra-high dose-rate electron beams.

Background: Ultra-high dose-rate (UHDR) irradiations (>40 Gy/s) have recently garnered interest in radiotherapy (RT) as they can trigger the so-called "FLASH" effect, namely a higher tolerance of normal tissues in comparison with conventional dose rates when a sufficiently high dose is delivered to the tissue. To transfer this to clinical RT treatments, adapted methods and practical tools for online dosimetry need to be developed. Ionization chambers remain the gold standards in RT but the charge recombination effects may be very significant at such high dose rates, limiting the use of some of these dosimeters.

Ultra-high dose rate dosimetry: Challenges and opportunities for FLASH radiation therapy.

The clinical translation of FLASH radiotherapy (RT) requires challenges related to dosimetry and beam monitoring of ultra-high dose rate (UHDR) beams to be addressed. Detectors currently in use suffer from saturation effects under UHDR regimes, requiring the introduction of correction factors. There is significant interest from the scientific community to identify the most reliable solutions and suitable experimental approaches for UHDR dosimetry.

Precise activity measurements of medical radionuclides using an ionization chamber: a case study with Terbium-161.

Background: Tb draws an increasing interest in nuclear medicine for therapeutic applications. More than 99% of the emitted gamma and X-rays of Tb have an energy below 100 keV. Consequently, precise activity measurement of Tb becomes inaccurate with radionuclide dose calibrators when using inappropriate containers or calibration factors to account for the attenuation of this low energy radiation.