Accurate dose mapping is essential for the performance qualification of electron beam sterilization of medical devices to ensure compliance with specified sterility assurance levels while avoiding material degradation. This study employs Monte Carlo models to compare alanine pellet and Ris & oslash; B3 film dosimeters with respect to their ability to measure surface dose as defined by a 1 mu m water layer present on the surface, and resolve dose gradients in 10 MeV electron beams. The findings show that while alanine pellets remain suitable for dose mapping when placed on surfaces with uniform irradiation and small dose gradients, thin film dosimeters are required for accurate surface dose mapping in complex geometries or where strong localized dose gradients are present, highlighting the need for application specific dosimeter selection.

BACKGROUND AND PURPOSE: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons. METHOD: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves. RESULTS AND DISCUSSION: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons. CONCLUSION: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs.

PurposeIonisation chamber based reference dosimetry in magnetic resonance linear accelerators (MRL) aimed for radiotherapy requires correction for recombination losses. Published studies have found that such corrections can be carried out using the two-voltage method. These studies have, however, not included comparison with recombination corrections based on the Niatel method, which can be seen as a robust reference method due to its clear separation of initial and volume recombination and its explicit account of the pulsed nature of the dose delivery. The primary objective of this work therefore was to carry out such a comparison.Materials and methodsFour Farmer-type chambers (PTW-30006 and PTW-30013) were placed in a water phantom in 1.5 T Elekta Unity MRL. The chambers were oriented antiparallel or perpendicular to the static magnetic field B0 and irradiated at a source-to-surface distance of 133.5 cm with a 10 × 10 cm2 field size.ResultsThe two-voltage method gave results in agreement (within 0.1%) with the recombination corrections derived from the Niatel method. The recombination corrections from three Niatel parameter sets (one based on a Varian Truebeam and two obtained directly in the MRL) deviated less than 0.1% from each other. A systematic shift in the recombination correction of less than 0.05% was observed if polarity corrections were not applied.ConclusionsThe study supports the use of the two-voltage method in MRLs based on its excellent agreement with the Niatel method. This work, therefore, complements existing knowledge as previous studies have not included a comparison with the Niatel method.

ObjectiveA favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam. However, the real advantage of proton therapy lies in the Spread-out Bragg Peak (SOBP), which allows for giving a high dose to a target with a limited dose to healthy tissue at the entrance of the beam. Therefore, a clinically relevant investigation of the FLASH effect would be of healthy tissues within a SOBP. Our study quantified the tissue-sparing effect of FLASH radiation on acute and late toxicity within an SOBP in a murine model.Material/MethodsRadiation-induced damage was assessed for acute and late toxicity in the same mice following irradiation with FLASH (Field dose rate of 60 Gy/s) or conventional (CONV, 0.34 Gy/s) dose rates. The right hindleg of unanesthetized female CDF1 mice was irradiated with single-fraction doses between 19.9-49.7 Gy for CONV and 30.4-65.9 Gy for FLASH with 5-8 mice per dose. The leg was placed in the middle of a 5 cm SOBP generated from a mono-energetic beam using a 2D range modulator. Acute skin toxicity quantified by hair loss, moist desquamation and toe separation was monitored daily within 29 days post-treatment. Late toxicity of fibrotic development measured by leg extendibility was monitored biweekly until 30 weeks post-treatment.ResultsComparison of acute skin toxicity following radiation indicated a tissue-sparing effect of FLASH compared to conventional single-fraction radiation with a mean protection ratio of 1.40 (1.35-1.46). Fibrotic development similarly indicated normal tissue sparing with a 1.18 (1.17-1.18) protection ratio. The acute skin toxicity tissue sparing was similar to data from entrance-beam irradiations of Sørensen et al. (4).ConclusionFull dose-response curves for acute and late toxicity after CONV and FLASH radiation were obtained. Radiation within the SOBP retains the normal-tissue-sparing effect of FLASH with a dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development.

Since their conception in the early 1990s, radioluminescence-based fibre-optic dosimeters (FODs) have attracted great interest for dosimetric applications in radiotherapy (RT). Over the years, many scintillating materials, both organic and inorganic, have been developed and tested by multiple research groups around the world. In parallel, reliable techniques for removing or subtracting the stem effect, one of the main drawbacks of FODs, have been proposed in the literature. To date, several prototype systems are widespread, some of which prove to be viable commercial solutions. This review aims to trace the efforts over the years that have enabled FODs to become reliable tools for dosimetry in the current RT procedures and promising options for future scenarios. After a first section devoted to a thorough discussion of the stem effect issue, the use of FODs in various applications of interest to RT, primarily small-field dosimetry and in vivo dosimetry, are addressed. Their use both in external beam RT, including hadrontherapy, and in brachytherapy are considered. A special focus is given to the peculiarities of MRI LINAC dosimetry and the contributions of FODs in this context. Finally, the state of the art concerning the development and characterization of FODs for monitoring ultra-high dose rate radiation beams, typical of FLASH therapy and microbeam RT are presented, highlighting the challenges still open.

Background and purpose: Daily target re-delineation in online adaptive radiotherapy (oART) introduces uncertainty. The aim of this study was to evaluate artificial intelligence (AI) generated contours and inter-observer target variation among radiotherapy technicians in cone-beam CT (CBCT) guided oART of bladder cancer. Materials and methods: For each of 10 consecutive patients treated with oART for bladder cancer, one CBCT was randomly selected and retrospectively included. The bladder (CTV-T) was AI-segmented (CTV-TAI). AI ). Seven radiotherapy technicians independently reviewed and edited CTV-TAI, AI , generating CTV-T-ADP. Contours were benchmarked against a ground truth contour (CTV-T-GT) delineated blindly from scratch. CTV-T-ADP and CTV-TAI AI were compared to CTV-T-GT using volume, dice similarity coefficient, and bidirectional local distance. Dose coverage (D99%>95 99% >95 %) of CTV-T-GT was evaluated for treatment plans optimized for CTV-TAI AI and CTVT (ADP) with clinical margins. Inter-observer variation among CTV-T-ADP was assessed using coefficient of variation and generalized conformity index. Results: CTV-T-GT ranged from 48.7 cm(3) to 211.6 cm3. 3 . The median [range] volume difference was 4.5 [-17.8, 42.4] cm(3) for CTV-T-ADP and-15.5 [-54.2, 4.3] cm(3) for CTV-TAI, AI , compared to CTV-T-GT. Corresponding dice similarity coefficients were 0.87 [0.71, 0.95] and 0.84 [0.64, 0.95]. CTV-T-GT was adequately covered in 68/70 plans optimized on CTV-T-ADP and in 6/10 plans optimized on CTV-TAI AI with clinical margins. The median [range] coefficient of variation was 0.08 [0.05, 0.11] and generalized conformity index was 0.78 [0.71, 0.88] among CTV-T-ADP. Conclusions: Target re-delineation in CBCT-guided oART of bladder cancer demonstrated non-isotropic inter-observer variation. Manual adjustment of AI-generated contours was necessary to cover ground truth targets.

PurposePreclinical studies have shown a preferential normal tissue sparing effect of FLASH radiotherapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biological effect of varying dose rates, time structure, and of introducing pauses in the dose delivery.Materials and MethodsThe right hind limbs of non-anaesthetized mice were irradiated in the entrance plateau of a PBS proton beam with 39.3 Gy. Experiment 1 with varying field dose rates (0.7- 80 Gy/s) without repainting, Experiment 2 with varying field dose rates (0.37- 80 Gy/s) with repainting, and Experiment 3 where the dose was split into 2, 3, 4 or 6 identical deliveries with 2 minutes pauses. In total 320 mice were included with 6-25 mice per group. The endpoints were skin toxicity of different levels up to 25 days after irradiation.ResultsThe Dose rate50, dose rate to induce response in 50% of the animals, depended on the level of skin toxicity, with the higher toxicity levels displaying a FLASH effect at 0.7-2 Gy/s. Repainting resulted in higher toxicity for the same field dose rate. Splitting the dose into two deliveries reduced the FLASH effect, and for three or more deliveries, the FLASH effect was almost abolished for lower grades of toxicity.ConclusionsThe dose rate that induced a FLASH effect varied for different skin toxicity levels, which are characterized by a differing degree of sensitivity to radiation dosage. Conclusions on a threshold for the dose rate needed to obtain a FLASH effect can therefore be influenced by the dose sensitivity of the used endpoint. Splitting the total dose into more deliveries compromised the FLASH effect. This can have an impact for fractionation as well as for regions where two or more FLASH fields overlap within the same treatment session.

BACKGROUND AND PURPOSE:In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy. Few in vivo studies have investigated the increasing RBE with increasing LET. This study aims to test the hypothesis that the RBE varies between endpoints and has a distal edge effect in vivo. MATERIALS AND METHODS:Unanesthetized micewere restrainedin jigs where their right hind legs were irradiated with a single dose of protons at the center (LET, all = 5.3 keV/μm) and distal edge (LET, all = 7.6 keV/μm) of a spread-out Bragg peak (SOBP). 6 MV photons were used as reference. The acute damage and skin toxicity were scored daily until day 30, and the late damage was evaluated using a joint contracture assay for one year after treatment. RESULTS:An acute damage RBE of 1.06 ± 0.02(1.02-1.10) and late damage RBE of 1.16 ± 0.08(1.00-1.32) were found, displaying an enhanced RBE for late damage in the center SOBP. The distal edge RBE for acute and late damage was 1.15 ± 0.02(1.10-1.19) and 1.26 ± 0.09(1.07-1.43), showing a similar center-to-distal edge RBE enhancement of 8 % and 9 % for acute and late damage. CONCLUSION:The findings demonstrate an increased RBE for late damage than acute damage and the distal edge effect is evident with increased RBE at the distal end of the proton SOBP in vivo.

Fiber coupled luminescence detectors based on organic plastic scintillators or inorganic materials such as Al2O3:C are suitable for dosimetry in strong magnetic fields as found in MR-linacs. The main finding of this work was that field-output factor measurements at the maximum dose point are less variable than if measured at the central beam axis (CAX). In contrast to plastic scintillators, Al2O3:C was found to have a yield of radioluminescence per dose that (within uncertainty) is independent of the magnetic field strength.

Current international protocols such as the IAEA/AAPM TRS-483 for small field dosimetry do not include recommendations for measurements in strong magnetic fields as found in MR-Linacs (i.e. megavoltage x-ray radiotherapy units with built-in magnetic resonance imaging). A EURAMET research project was therefore launched to support the traceability of such measurements and to contribute to the metrological basis for future recommendations. Given the high degree of water equivalence and the small size of fiber-coupled plastic scintillators, one objective of the project was to study the suitability of this detector type for dosimetry in MR-Linacs and to demonstrate their use in a clinical environment. This manuscript reports results of that work. A protocol for measuring field output factors with plastic scintillation detectors was developed. The protocol is based on calibration of the scintillators directly in a water phantom positioned in the MR-Linac rather than in a water-equivalent solid phantom as has been a common technique for conventional linacs. A detailed uncertainty budget was established involving all known sources of uncertainty including the systematic influence of light attenuation through the fiber when measuring in different field sizes. The protocol was used to measure field output factors at five MR-Linac’s (four Viewray MRIdian’s and one Elekta Unity). The protocol showed a high level of robustness leading to a less than 0.3 % deviation between field output factors calculated based on calibration data obtained before or after the field-output factor measurements. The correction for light attenuation was less than 0.4 % for all fields measured but showed a systematic offset, with larger corrections needed for small field sizes.This robustness of the protocol was further demonstrated by the closeness of agreement (agreement within uncertainty) for field-output factor measurements with two different scintillators (BCF-12 and BCF-60) for square fields (size: 0.83 cm x 0.83 cm or larger) in four nominally identical Viewray MRIdian's. To test the accuracy of the scintillator measurements, the system was used for characterization of a PTW 60019 micro diamond detector in a Viewray MRIdian. Scintillator based correction factors for output factor measurements with the micro diamond detector were found to be in agreement with independent Monte-Carlo computations. The study therefore supports that plastic scintillation detectors are an excellent option for measuring field output factors in MR-Linacs.

BackgroundThe purpose of this study was to investigate acute normal tissue responses in the head and neck region following proton- or X-irradiation of a murine model.Materials and methodsFemale C57BL/6J mice were irradiated with protons (25 or 60 MeV) or X-rays (100 kV). The radiation field covered the oral cavity and the major salivary glands. For protons, two different treatment plans were used, either with the Bragg Peak in the middle of the mouse (BP) or outside the mouse (transmission mode; TM). Delivered physical doses were 41, 45, and 65 Gy given in 6, 7, and 10 fractions for BP, TM, and X-rays, respectively. Alanine dosimetry was used to assess delivered doses. Oral mucositis and dermatitis were scored using CTC v.2.0-based tables. Saliva was collected at baseline, right after end of irradiation, and at day 35.ResultsThe measured dose distribution for protons (TM) and X-rays was very similar. Oral mucositis appeared earlier, had a higher score and was found in a higher percentage of mice after proton irradiation compared to X-irradiation. Dermatitis, on the other hand, had a similar appearance after protons and X-rays. Compared to controls, saliva production was lower right after termination of proton- and X-irradiation. The BP group demonstrated saliva recovery compared to the TM and X-ray group at day 35.ConclusionWith lower delivered doses, proton irradiation resulted in similar skin reactions and increased oral mucositis compared to X-irradiation. This indicates that the relative biological effectiveness of protons for acute tissue responses in the mouse head and neck is greater than the clinical standard of 1.1. Thus, there is a need for further investigations of the biological effect of protons in normal tissues.

The combination of magnetic resonance (MR) imaging and linear accelerators (linacs) into MR-Linacs enables continuous MR imaging and advanced gated treatments of patients. Previously, a dose-rate transient (∼8% reduced dose rate during the initial 0.5 s of each beam) was identified for a Viewray MRIdian MR-Linac (Klavsenet al2022Radiation Measurement106759). Here, the dose-rate transient is studied in more detail at four linacs of the same type at different hospitals. The implications of dose-rate transients were examined for gated treatments. The dose-rate transients were investigated using dose-per pulse measurements with organic plastic scintillators in three experiments: (i) A gated treatment with the scintillator placed in a moving target in a dynamic phantom, (ii) a gated treatment with the same dynamic conditions but with the scintillator placed in a stationary target, and (iii) measurements in a water-equivalent material to examine beam quality deviations at a dose-per-pulse basis. Gated treatments (i) compared with non-gated treatments with a static target in the same setup showed a broadening of accumulated dose profiles due to motion (dose smearing). The linac with the largest dose-rate transient had a reduced accumulated dose of up to (3.1 ± 0.65) % in the center of the PTV due to the combined dose smearing and dose-rate transient effect. Dose-rate transients were found to vary between different machines. Two MR-Linacs showed initial dose-rate transients that could not be identified from conventional linearity tests. The source of the transients includes an initial change in photon fluence rate and an initial change in x-ray beam quality. For gated treatments, this caused a reduction of more than 1% dose delivered at the central part of the beam for the studied, cyclic-motion treatment plan. Quality assurance of this effect should be considered when gated treatment with the Viewray MRIdian is implemented clinically.

Organic plastic scintillators are of interest for ionizing radiation dosimetry in megavoltage photon beams because plastic scintillators have a mass density very similar to that of water. This leads to insignificant perturbation of the electron fluence at the point of measurement in a water phantom. This feature is a benefit for dosimetry in strong magnetic fields (e.g., 1.5 T) as found in linacs with magnetic resonance imaging. The objective of this work was to quantify if the light yield per dose for the scintillating fiber BCF-60 material from Saint-Gobain Ceramics and Plastics Inc. is constant regardless of the magnetic flux density. This question is of importance for establishing traceable measurement in MR linacs using this detector type. Experiments were carried out using an accelerator combined with an electromagnet (max 0.7 T). Scintillator probes were read out using chromatic stem-removal techniques based on two optical channels or full spectral information. Reference dosimetry was carried out with PTW31010 and PTW31021 ionization chambers. TOPAS/GEANT4 was used for modelling. The light yield per dose for the BCF-60 was found to be strongly influenced by the magnitude of the magnetic field from about 1 mT to 0.7 T. The light yield per dose increased (1.3 ± 0.2)% (k = 1) from 1 mT to 10 mT and it increased (4.5 ± 0.9)% (k = 1) from 0 T to 0.7 T. Previous studies of the influence of magnetic fields on medical scintillator dosimetry have been unable to clearly identify if observed changes in scintillator response with magnetic field strength were related to changes in dose, stem signal removal, or scintillator light yield. In the current study of BCF-60, we see a clear change in light yield with magnetic field, and none of the other effects.

Background and purpose: Daily plan adaptations could take the dose delivered in previous fractions into account. Due to high dose delivered per fraction, low number of fractions, steep dose gradients, and large interfractional organ deformations, this might be particularly important for liver SBRT. This study inves-tigates inter-algorithm variation of interfractional dose accumulation for MR-guided liver SBRT.Materials and methods: We assessed 27 consecutive MR-guided liver SBRT treatments of 67.5 Gy in three (n = 15) or 50 Gy in five fractions (n = 12), both prescribed to the GTV. We calculated fraction doses on daily patient anatomy, warped these doses to the simulation MRI using seven different algorithms, and accumulated the warped doses. Thus, we obtained differences in planned doses and warped or accumu-lated doses for each algorithm. This enabled us to calculate the inter-algorithm variations in warped doses per fraction and in accumulated doses per treatment course.Results: The four intensity-based algorithms were more consistent with planned PTV dose than affine or contour-based algorithms. The mean (range) variation of the dose difference for PTV D95% due to dose warping by these intensity-based algorithms was 10.4 percentage points (0.3 to 43.7) between fractions and 8.6 (0.3 to 24.9) between accumulated treatment doses. As seen by these ranges, the variation was very dependent on the patient and the fraction being analyzed. Nevertheless, no correlations between patient or plan characteristics on the one hand and inter-algorithm dose warping variation on the other hand was found.Conclusion: Inter-algorithm dose accumulation variation is highly patient-and fraction-dependent for MR-guided liver SBRT. We advise against trusting a single algorithm for dose accumulation in liver SBRT.(c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 182 (2023) 109448 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Determination of beam quality correction factors is crucial for performing accurate alanine pellet dosimetry in non-reference fields. For some complex irradiation geometries, interpolation from literature data is more convenient than an experimental approach to establish these factors. Here we investigate the validity of extracting quality correction factors from literature data based on information on beam qualifiers such as half-value layer (HVL) or effective energy ${E}_{\text{eff}}$. A combination of Monte Carlo calculated dose ratios and a microdosimetric assessment of the relative efficiency allows for numerical evaluation of quality correction factors for a wide array of X-ray qualities. The computational analysis demonstrates that the average energy of the X-ray beam is optimal for characterizing the relative response. Special care should be taken when using the common X-ray beam qualifiers HVL or ${E}_{\text{eff}}$ to determine quality correction factors from literature data.

PURPOSE:Preclinical studies indicate a normal tissue sparing effect when ultra-high dose rate (FLASH) radiation is used, while tumor response is maintained. This differential response has promising perspectives for improved clinical outcome. This study investigates tumor control and normal tissue toxicity of pencil beam scanning (PBS) proton FLASH in a mouse model. METHODS AND MATERIALS:Tumor bearing hind limbs of non-anaesthetized CDF1 mice were irradiated in a single fraction with a PBS proton beam using either conventional (CONV) dose rate (0.33-0.63 Gy/s field dose rate, 244 MeV) or FLASH (71-89 Gy/s field dose rate, 250 MeV). 162 mice with a C3H mouse mammary carcinoma subcutaneously implanted in the foot were irradiated with physical doses of 40-60 Gy (8-14 mice per dose point). The endpoints were tumor control (TC) assessed as no recurrent tumor at 90 days after treatment, the level of acute moist desquamation (MD) to the skin of the foot within 25 days post irradiation, and radiation induced fibrosis (RIF) within 24 weeks post irradiation. RESULTS:TCD50 (dose for 50% tumor control) was similar for CONV and FLASH with values (and 95% confidence intervals) of 49.1 (47.0-51.4) Gy for CONV and 51.3 (48.6-54.2) Gy for FLASH. RIF analysis was restricted to mice with tumor control. Both endpoints showed distinct normal tissue sparing effect of proton FLASH with MDD50 (dose for 50% of mice displaying moist desquamation) of <40.1 Gy for CONV and 52.3 (50.0-54.6) Gy for FLASH, (dose modifying factor at least 1.3) and FD50 (dose for 50% of mice displaying fibrosis) of 48.6 (43.2-50.8) Gy for CONV and 55.6 (52.5-60.1) Gy for FLASH (dose modifying factor of 1.14). CONCLUSIONS:FLASH had the same tumor control as CONV, but reduced normal tissue damage assessed as acute skin damage and radiation induced fibrosis.