PURPOSE:Understanding the energy-dependent variation in relative biological effectiveness (RBE) is crucial for both neutron radioprotection and therapeutic applications. This study aims to evaluate the biological impact of neutron irradiation on A375 human melanoma cells using neutron beams of different energy ranges, with the goal of contributing to the optimization of radioprotection standards and the advancement of neutron-based cancer therapies, such as Boron Neutron Capture Therapy (BNCT). MATERIAL AND METHODS:A375 human melanoma cells were irradiated using two distinct neutron beams: one in the keV range at the CNA facility in Sevilla, and another in the MeV range at the CIEMAT facility in Madrid. Clonogenic assays were performed to evaluate cellular response and determine RBE values. The biological effects were assessed and compared with previously obtained data from thermal-equivalent neutron energies and reference photon irradiation. RESULTS:The MeV-range neutron beam induced slightly stronger biological effects than the keV-range beam, but the observed RBE difference was notably smaller than the ∼50% gap predicted by ICRP models. Instead, the experimental trend closely aligned with previous theoretical RBE estimations based on secondary particle contributions. These results underscore the need to reevaluate current radioprotection weighting factors and support the refinement of neutron-based therapeutic protocols.

The aim of this work is to present a reproducible methodology for the evaluation of total equivalent doses in organs during proton therapy facilities. The methodology is based on measuring the dose equivalent in representative locations inside an anthropomorphic phantom where photon and neutron dosimeters were inserted. The Monte Carlo simulation was needed for obtaining neutron energy distribution inside the phantom. The methodology was implemented for a head irradiation case in the passive proton beam of iThemba Labs (South Africa). Thermoluminescent dosimeter (TLD)-600 and TLD-700 pairs were used as dosimeters inside the phantom and GEANT code for simulations. In addition, Bonner sphere spectrometry was performed inside the treatment room to obtain the neutron spectra, some relevant neutron dosimetric quantities per treatment Gy, and a percentual distribution of neutron fluence and ambient dose equivalent in four energy groups, at two locations. The neutron spectrum at one of those locations was also simulated so that a reasonable agreement between simulation and measurement allowed a validation of the simulation. Results showed that the total out-of-field dose equivalent inside the phantom ranged from 1.4 to 0.28 mSv/Gy, mainly due to the neutron contribution and with a small contribution from photons, 10% on average. The order of magnitude of the equivalent dose in organs was similar, displaying a slow reduction in values as the organ is farther from the target volume. These values were in agreement with those found by other authors in other passive beam facilities under similar irradiation and measurement conditions.

COPYRIGHT © 2022 Sánchez-Nieto, Stolarczyk, Dasu, Newhauser and SánchezDoblado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 05 December 2022 DOI 10.3389/fonc.2022.1076792

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

PurposeNeutron peripheral contamination in high-energy radiotherapy implies an increase of secondary radiation-induced cancer risk. Although peripheral neutron dose (PND) has been evaluated in organs, few studies have been performed regarding patient size. This work aims to improve an existing methodology for adult patient PND estimations to generalize it to young and children, for its implementation in treatment planning systems (TPS).MethodsAs a first step, we aimed to generalize the previous model to be usable with any thermal neutron detector. Then, taking into account total neutron spectra and dose-to-point thermal neutron fluence measurements for three phantom sizes (adult, teen and child) and two common treatment locations (H&N and abdomen), the new model was proposed. It represents an upgraded parameterization and extension of the existing one, including patient anatomy. Finally, comparison between estimations and measurements, as well as validation against the original model, was carried out for 510 measured patients.ResultsConcordance found between experimental and theoretical estimations makes us confident about later implementation in treatment planning systems. Comparison among the previous and upgraded models shows no significant differences for the adult case. However, an important underestimation (34.1% on average) can be observed regarding child case for the original one.ConclusionsAn improved generalization of an existing PND model, considering patient anatomy has been validated and used in real patients. The final methodology is easily implementable in clinical routine and TPS thanks to the ready availability of input parameters (patient height and weight, high-energy MU and facility characterization).

One of the major causes of secondary malignancies after radiotherapy treatments are peripheral doses, known to increase for some newer techniques (such as IMRT or VMAT). For accelerators operating above 10MV, neutrons can represent important contribution to peripheral doses. This neutron contamination can be measured using different passive or active techniques, available in the literature. As far as active (or direct-reading) procedures are concerned, a major issue is represented by their parasitic photon sensitivity, which can significantly affect the measurement when the point of test is located near to the field-edge. This work proposes a simple method to estimate the unwanted photon contribution to these neutrons. As a relevant case study, the use of a recently neutron sensor for "in-phantom" measurements in high-energy machines was considered. The method, called "Dual Energy Photon Subtraction" (DEPS), requires pairs of measurements performed for the same treatment, in low-energy (6MV) and high energy (e.g. 15MV) fields. It assumes that the peripheral photon dose (PPD) at a fixed point in a phantom, normalized to the unit photon dose at the isocenter, does not depend on the treatment energy. Measurements with ionization chamber and Monte Carlo simulations were used to evaluate the validity of this hypothesis. DEPS method was compared to already published correction methods, such as the use of neutron absorber materials. In addition to its simplicity, an advantage of DEPs procedure is that it can be applied to any radiotherapy machine.

PurposeBiological treatment plan evaluation does not currently consider second cancer induction from peripheral doses associated to photon radiotherapy. The aim is to propose a methodology to characterize the therapeutic window by means of an integral radiobiological approach, which considers not only Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) but also Secondary Cancer Probability (SCP).MethodsUncomplicated and Cancer-Free Control Probability (UCFCP) function has been proposed assuming a statistically uncorrelated response for tumour and normal tissues. The Poisson’s and Lyman’s models were chosen for TCP and NTCP calculations, respectively. SCP was modelled as the summation of risks associated to photon and neutron irradiation of radiosensitive organs. For the medium (>4Gy) and low dose regions, mechanistic and linear secondary cancer risks models were used, respectively. Two conformal and intensity-modulated prostate plans at 15MV (same prescription dose) were selected to illustrate the UCFCP features.ResultsUCFCP exhibits a bell-shaped behaviour with its maximum inside the therapeutic window. SCP values were not different for the plans analysed (∼2.4%) and agreed with published epidemiological results. Therefore, main differences in UCFCP came from differences in rectal NTCP (18% vs 9% for 3D-CRT and IMRT, respectively). According to UCFCP values, the evaluated IMRT plan ranked first.ConclusionsThe level of SCP was found to be similar to that of NTCP complications which reinforces the importance of considering second cancer risks as part of the possible late sequelae due to treatment. Previous concerns about the effect of peripheral radiation, especially neutrons, in the induction of secondary cancers can be evaluated by quantifying the UCFCP.

PURPOSE:The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter "immeasurable" by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor wR, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with wR. METHODS:Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. RESULTS:The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. CONCLUSIONS:Quality factor can be replaced by the radiation weighting factor in the evaluation of dose equivalent in radiotherapy environments simplifying the practical procedure.

Introduction Peripheral doses are directly related to second cancer risk after radiotherapy. Our group developed a methodology to estimate neutron contribution to peripheral organ doses by terms of two general models, namely abdomen and head and neck [PMB-2012;57:6167–6191]. Purpose This work aims to verify the validity of these models in real treatments, in order to evaluate the need of further improvements for specific locations beside the two generic ones. Materials and methods Neutron doses were calculated in 12 representative organs from measured thermal neutron fluences with TNRD detectors at 16 points inside the phantom [MedPhys-2014;41:112105], for two high energy (15 MV) treatments (lung and prostate). Following the methodology described in [R&O-2013;107:234–241], these neutron doses were estimated by terms of number of delivered MU and facility characterization. Abdomen model was used for the prostate case while both (abdomen and head&neck) for the lung one (due to isocenter position respect to models). Then measurements have been compared to estimations obtained with the prediction models [MedPhys-2015;42:276–281]. Results Values generally agreed within the 30% uncertainty range established for the models and the 15% for the measurement. Abdomen model has shown to fit better for the lung. Further studies should be needed to improve generic models in some specific locations such as skin or organs close to the field-edge. Conclusion The generic model has shown to be good enough to cover frequent high-energy specific treatments as those studied here. It seems to be no need of more specific models, while some improvements have to bee done for particular points.

3rd ESTRO Forum 2015 S761 Table 1.Comparison of D4 γ results, DC γ and DC DD for lung plans with and without density override (DO) in the body or lung volume. Conclusions:The DC EPID in vivo dosimetry system was successfully implemented at our hospital.Corresponding gamma pass/fail criteria for DC and D4 phantom measurements were established.A solution was found to overcome dose reconstruction issues in strong heterogeneous regions.The main limitation of the system remains the size of the EPID panel.

3rd ESTRO Forum 2015 S735 in-vitro cell survival experiments after photon or ion irradiation.For each radiation quality in the PIDE-Database, the corresponding ICS distributions (ICSD) were calculated with the PTB Track structure code (PTra) [4, 5] for specific nanodosimetric parameters, such as size, shape and material composition of the specified target volume (STV), as well as its distance and direction with respect to the particle beam.Results: Nanodosimetric quantities were calculated from the aforementioned ICSDs (i.e. the mean ionisation cluster size M 1 , or the cumulative probability distribution F K of ICS, given the probability that an ICS of K or larger is produced in the target volume).The ascertained correlations to the biological data will be presented.Conclusions: The database application is a useful resource for investigating the range of validity of the nanodosimetric approach.

A new thermal neutron detector (TNRD), developed for nuclear research, has shown to be effective for clinical use in peripheral neutron dose estimation, either in patient and ‘in-phantom’ measurements. This work shows some TNRD difficulties when adapting it to radiotherapy environments, mainly due to the fact that it has shown structural limitations. Two problems have been studied: (1) the influence of cable lengthening, necessary to be operative in a radiotherapy environment and (2) cable irradiation during the measurements. As we are measuring very small signals, we have to take into account not only these two facts but also the quality of the materials and connectors used. Thus, we studied cable elongation and irradiation influences in conventional and extreme situations once the setup was improved, in order to avoid uncertainties which could be of the order of the signal. Mean deviations of -0.15% from the original TNRD cable extension have been noticed. For the wide variety of conditions tested, in terms of both dose delivered and setup of the radiotherapy exposure, uncertainties smaller than 1.2% have been estimated.

PURPOSE:Knowing the contribution of neutron to collateral effects in treatments is both a complex and a mandatory task. This work aims to present an operative procedure for neutron estimates in any facility using a neutron digital detector.METHODS:The authors' previous work established a linear relationship between the total second cancer risk due to neutrons (TR(n)) and the number of MU of the treatment. Given that the digital detector also presents linearity with MU, its response can be used to determine the TR(n) per unit MU, denoted as m, normally associated to a generic Linac model and radiotherapy facility. Thus, from the number of MU of each patient treatment, the associated risk can be estimated. The feasibility of the procedure was tested by applying it in eight facilities; patients were evaluated as well.RESULTS:From the reading of the detector under selected irradiation conditions, m values were obtained for different machines, ranging from 0.25 × 10(-4)% per MU for an Elekta Axesse at 10 MV to 6.5 × 10(-4)% per MU for a Varian Clinac at 18 MV. Using these values, TR(n) of patients was estimated in each facility and compared to that from the individual evaluation. Differences were within the range of uncertainty of the authors' methodology of equivalent dose and risk estimations.CONCLUSIONS:The procedure presented here allows an easy estimation of the second cancer risk due to neutrons for any patient, given the number of MU of the treatment. It will enable the consideration of this information when selecting the optimal treatment for a patient by its implementation in the treatment planning system.

A newly TPS algorithm, implemented in Pinnacle(3), has been developed for peripheral neutron dose estimation for radiotherapy patients. The script gives doses in several organs according to gender, treatment location and delivered high energy monitor units. In order to validate these estimations, doses for a total of 119 patients were calculated with Pinnacle3 TPS script, and compared to the experimental measurements with the new Thermal Neutron Digital Detector (TNRD). The studied patients, cover a wide range of pathologies for three different linacs. The comparison shows that with the implemented script we obtain a good correlation between measurement and theoretical values. On the other hand, periodic neutron characterization of the facility should be considered for better estimations.

3rd ESTRO Forum 2015 S869 Siemens applicators.For Siemens Primus with an applicator size of 10x10cm², this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6,9,12 and 18MeV electron beams, respectively, doubled for 6x6cm² field size.For Siemens Oncor, with the above applicator size, this peak dose reaches 0.8%, 1%, 1.4% and 1.5% of Dmax for 6,9,12 and 14 MeV, respectively, doubled for 20x20cm².In contrast for Varian 2300C/D, the doses at 15cm from field edge are 0.3%, 0.5%, 0.6% and 1.1% of Dmax for 6, 9, 12 and 18MeV, respectively.No peak dose spot is evidenced for Varian applicator.Measurements made at 10cm depth show that, depending on beam energy, applicator size, collimator size, and out-of-field distance, the peripheral dose represents 0.01% to 1% of Dmax.Conclusions: This work analyzes peripheral doses for different electron beams energies and three different applicator types.It evidences that depending on beam energy, applicator size and type, the peak dose at 15cm from field edge ranges from 0.3-2.7% of the Dmax In certain circumstances the peripheral doses from electron beams may be comparable to values reported for photon beams.Our results should be considered in the optimization of treatment planning and also in studies exploring RT long term effects.

Purpose:Previous measurements with Bonner spheres1 showed that normalized neutron spectra are equal for the majority of the existing linacs2. This information, in addition to thermal neutron fluences obtained in the characterization procedure33, would allow to estimate neutron doses accidentally received by exposed workers, without the need of an extra experimental measurement.Methods:Monte Carlo (MC) simulations demonstrated that the thermal neutron fluence distribution inside the bunker is quite uniform, as a consequence of multiple scatter in the walls⁴. Although inverse square law is approximately valid for the fast component, a more precise calculation could be obtained with a generic fast fluence distribution map around the linac, from MC simulations⁴. Thus, measurements of thermal neutron fluences performed during the characterization procedure3, together with a generic unitary spectra2, would allow to estimate the total neutron fluences and H*(10) at any point⁵. As an example, we compared estimations with Bonner sphere measurements1, for two points in five facilities: 3 Siemens (15–23 MV), Elekta (15 MV) and Varian (15 MV).Results:Thermal neutron fluences obtained from characterization, are within (0.2–1.6×10⁶) cm−2•Gy−1 for the five studied facilities. This implies ambient equivalent doses ranging from (0.27–2.01) mSv/Gy 50 cm far from the isocenter and (0.03–0.26) mSv/Gy at detector location with an average deviation of ±12.1% respect to Bonner measurements.Conclusion:The good results obtained demonstrate that neutron fluence and H*(10) can be estimated based on: (a) characterization procedure established for patient risk estimation in each facility, (b) generic unitary neutron spectrum and (c) generic MC map distribution of the fast component.[1] Radiat. Meas (2010) 45: 1391 – 1397; [2] Phys. Med. Biol (2012) 5 7:6167–6191; [3] Med. Phys (2015) 42:276 ‐ 281. [4] IFMBE (2012) 39: 1245–1248. [5] ICRU Report 57 (1998)