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Comparison between average CT planned and CBCT recalculated dose metrics (Gy) for the target structures. All doses are reported as means [standard deviation] in units of Gy

Time to reach 2-times starting tumor volume (TGTV2) increases linearly with increasing uniform radiation dose.

An example of distribution of hypoxia tracer HX4 (3 hours post injection) and FDG (2 hours post injection) in the same rhabdomyosarcoma bearing rat 20 hours apart, demonstrating large overlap between the tracers. White contours correspond to 30% of the GTV (magenta contours) with the highest SUV. Dice similarity coefficient is 0.79 for this example.

Experimental design. Hot Boost (Cold Boost ) 40% (60%) indicates 40% (60%) higher radiation dose to tumor sub-volume with the highest (lowest) FDG uptake than to the rest of the tumor.

Purpose: We tested therapeutic efficacy of two dose painting strategies of applying higher radiation dose to tumor subvolumes with high FDG uptake (biologic target volume, BTV): dose escalation and dose redistribution. We also investigated whether tumor response was determined by the highest dose in BTV or the lowest dose in gross tumor volume (GTV).Experimental Design: FDG uptake was evaluated in rat rhabdomyosarcomas prior to irradiation. BTV was defined as 30% of GTV with the highest (BTVhot) or lowest (BTVcold) uptake. To test efficacy of dose escalation, tumor response (time to reach two times starting tumor volume, TGTV2) to Hot Boost irradiation (40% higher dose to BTVhot) was compared with Cold Boost (40% higher dose to BTVcold), while mean dose to GTV remained 12 Gy. To test efficacy of dose redistribution, TGTV2 after Hot Boost was compared with uniform irradiation with the same mean dose (8 or 12 Gy).Results: TGTV2 after 12 Gy delivered heterogeneously (Hot and Cold Boost) or uniformly were not significantly different: 20.2, 19.5, and 20.6 days, respectively. Dose redistribution (Hot Boost) with 8 Gy resulted in faster tumor regrowth as compared with uniform irradiation (13.3 vs. 17.1 days; P = 0.026). Further increase in dose gradient to 60% led to a more pronounced decrease in TGTV2 (10.9 days; P < 0.0001).Conclusions: Dose escalation effect was independent of FDG uptake in target tumor volume, while dose redistribution was detrimental in this tumor model for dose levels applied here. Our data are consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. Clin Cancer Res; 21(24); 5511–8. ©2015 AACR.

Objective. There is a continuous increase in 3D printing applications in several fields including medical imaging and radiotherapy. Although there are numerous advantages of using 3D printing for the development of customized phantoms, bolus, quality assurance devices and other clinical applications, material properties are not well known and printer settings can affect considerably the properties (e.g. density, isotropy and homogeneity) of the printed parts. This study aims to evaluate several materials and printer properties to identify a range of tissue-mimicking materials. Approach. Dual-energy CT was used to obtain the effective atomic number (Z eff) and relative electron density (RED) for thirty-one different materials including different colours of the same filament from the same manufacturer and the same type of filament from different manufacturers. In addition, a custom bone equivalent filament was developed and evaluated since a high-density filament with a composition similar to bone is not commercially available. Printing settings such as infill density, infill pattern, layer height and nozzle size were also evaluated. Main results. Large differences were observed for HU (288), RED (>10%) and Z eff (>50%) for different colours of the same filament due to the colour pigment. Results show a wide HU variation (−714 to 1104), RED (0.277 to 1.480) and Z eff (5.22 to 12.39) between the printed samples with some materials being comparable to commercial tissue-mimicking materials and good substitutes to a range of materials from lung to bone. Printer settings can result in directional dependency and significantly affect the homogeneity of the samples. Significance. The use of DECT to extract RED, and Z eff allows for quantitative imaging and dosimetry using 3D printed materials equivalent to certified tissue-mimicking tissues.

PURPOSE: Even though High Dose Rate (HDR) brachytherapy has good treatment outcomes in different treatment sites, treatment verification is far from widely implemented because of a lack of easily available solutions. Previously it has been shown that an imaging panel (IP) near the patient can be used to determine treatment parameters such as the dwell time and source positions in a single material pelvic phantom. In this study we will use a heterogeneous head phantom to test this IP approach, and simulate common treatment errors to assess the sensitivity and specificity of the error-detecting capabilities of the IP. METHODS AND MATERIALS: A heterogeneous head-phantom consisting of soft tissue and bone equivalent materials was 3D-printed to simulate a base of tongue treatment. An High Dose Rate treatment plan with 3 different catheters was used to simulate a treatment delivery, using dwell times ranging from 0.3 s to 4 s and inter-dwell distances of 2 mm. The IP was used to measure dwell times, positions and detect simulated errors. Measured dwell times and positions were used to calculate the delivered dose. RESULTS: Dwell times could be determined within 0.1 s. Source positions were measured with submillimeter accuracy in the plane of the IP, and average distance accuracy of 1.7 mm in three dimensions. All simulated treatment errors (catheter swap, catheter shift, afterloader errors) were detected. Dose calculations show slightly different distributions with the measured dwell positions and dwell times (gamma pass rate for 1 mm/1% of 96.5%). CONCLUSIONS: Using an IP, it was possible to verify the treatment in a real-istic heterogeneous phantom and detect certain treatment errors. (c) 2022 The Au-thors. Published by Elsevier Inc. on behalf of American Brachytherapy Society. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) We thank Dr. Murillo Bellezzo for his help with the measurements, and Dr. Mark Podesta for his helpful Matlab functions.

PURPOSE: Dose escalation yields higher complete response to rectal tumors, which may enable the omission of surgery. Dose escalation using 50 kVp contact x-ray brachytherapy (CXB) allow the treatment of a selective volume, resulting in low toxicity and organs-at-risk preservation. However, the use of CXB devices is limited because of its high cost and lack of treatment planning tools. Hence, the MAASTRO applicator (for HDR Ir-192 sources) was developed and characterized by measurements and Monte Carlo simulations to be a cost-effective alternative to CXB devices.METHODS AND MATERIALS: A cylindrical applicator with lateral shielding was designed to be used with a rectoscope using its tip as treatment surface. Both the applicator and the rectoscope have a slanted edge to potentially allow easier placement against tumors. The applicator design was achieved by Monte Carlo modeling and validated experimentally with film dosimetry, using the Papillon 50 (P50) device as reference.RESULTS: The applicator delivers CXB doses in less than 9 min using a 20375 U source for a treatment area of approximately 20 x 20 mm(2) at 2 mm depth. Normalized at 2 mm, the dose falloff for depths of 0 mm, 5 mm, and 10 mm are 130%, 70%, and 43% for the P50 and 140%, 67%, and 38% for the MAASTRO applicator, respectively.CONCLUSIONS: The MAASTRO applicator was designed to use HDR Ir-192 sources to deliver a dose distribution similar to those of CXB devices. The applicator may provide a cost-effective solution for endoluminal boosting with clinical treatment planning system integration. (C) 2020 Published by Elsevier Inc. on behalf of American Brachytherapy Society.

FLASH radiation therapy is a novel technique combining ultra-high dose rates (UHDR) with very short treatment times to strongly decrease normal tissue toxicity while preserving the anti-tumoral effect. However, the radiobiological mechanisms and exact conditions for obtaining the FLASH-effect are still under investigation. There are strong indications that parameters defining the beam structure, such as dose per pulse, instantaneous dose rate and pulse repetition frequency (PRF) are of importance. UHDR irradiations therefore come with dosimetric challenges, including both dose assessment and temporal ones. In this work, a first characterization of 6 real-time point scintillating dosimeters with 5 phosphors (Al2O3:C,Mg; Y2O3:Eu; Al2O3:C; (C38H34P2)MnBr4 and (C38H34P2)MnCl4, was performed in an UHDR pulsed electron beam. The dose rate independence of the calibration was tested by calibrating the detector at conventional and UHDR. Dose rate dependence was observed, however, further investigation, including intermediate dose rates, is needed. Linearity of the response with dose was tested by varying the number of pulses and a linearity with R-2 > 0.9989 was observed up to at least 200 Gy. Dose per pulse linearity was investigated by variation of the pulse length and SSD. All point scintillators showed saturation effects up to some extent and the instantaneous dose rate dependence was confirmed. A PRF dependence was observed for the Al2O3:C,Mg and Al2O3:C- based point scintillators. This was expected as the luminescence decay time of these materials exceeds the inter-pulse time.

Objective. Microdosimetry offers a fast tool for radiation quality (RQ) verification to be implemented in treatment planning systems in proton therapy based on variable LET or RBE to move forward from the use of a fixed RBE of 1.1. It is known that the RBE of protons can increase up to 50% higher than that value in the last few millimetres of their range. Microdosimetry can be performed both experimentally and by means of Monte Carlo (MC) simulations. This paper has the aim of comparing the two approaches. Approach. Experimental measurements have been performed using a miniaturized Tissue equivalent proportional counter developed at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics with the aim of being used as RQ monitors for high intensity beams. MC simulations have been performed using the microdosimetric extension of TOPAS which provides optimized parameters and scorers for this application. Main results. Simulations were compared with experimental microdosimetric spectra in terms of shape of the spectra and their average values. Moreover, the latter have been investigated as possible estimators of LET obtained with the same MC code. The shape of the spectra is in general consistent with the experimental distributions and the average values of the distributions in both cases can predict the RQ increase with depth. Significance. This study aims at the comparison of microdosimetric spectra obtained from both experimental measurements and the microdosimetric extension of TOPAS in the same radiation field.

Inorganic Polymers (IPs) are interesting alternative binder materials to Ordinary Portland Cement (OPC). They could be potentially used in applications such as nuclear safety structures and radioactive waste management since they are highly chemically and thermally resistant. However, their chemical and mechanical stability still has to be proven when irradiated at the very early age. This study investigated the effect of gamma irradiation on the mechanical and microstructural properties of IPs cured for 1 h, 24 h or 28 days. For that purpose, IPs were irradiated using different dose rates (1.6 Gy/h, 7.1 Gy/h, 152 Gy/h and 2 kGy/h) until different absorbed doses with a maximum of 624 kGy. The effects were evaluated by means of compressive strength tests, microstructural analysis by image analysis, porosity analysis (water absorption and MIP), thermogravimetric analysis (TGA) and infrared spectrometry. For each irradiation test, non-irradiated samples were kept as a reference at the same environmental conditions as the irradiated samples. The results were compared with similar studies on OPC-based samples. At low doses (

PURPOSE: The Bravos afterloader system was released by Varian Medical Systems in October of 2018 for high-dose-rate brachytherapy with Ir-192 sources, containing new features such as the CamScale (a new device for daily quality assurance and system recalibration), channel length verification, and different settings for rigid and flexible applicators. This study mechanically evaluated the Bravos system precision and accuracy for clinically relevant scenarios, using dummy sources.METHODS AND MATERIALS: The system was evaluated after three sets of experiments: (1) The CamScale was used to verify inter- and infra-channel dwelling variability and system calibration; (2) A high-speed camera was used to verify the source simulation cable movement inside a transparent quality assurance device, where dwell positions, dwell times, transit times, speed profiles, and accelerations were measured; (3) The source movement inside clinical applicators was captured with an imaging panel while being exposed to an external kV source. Measured and planned dwell positions and times were compared.RESULTS: Maximum deviations between planned and measured dwell positions and times for the source cable were 0.4 mm for the CamScale measurements and 0.07 seconds for the high-speed camera measurements. Mean dwell position deviations inside clinical applicators were below 1.2 mm for all applicators except the ring that required an offset correction of 1 mm to achieve a mean deviation of 0.4 mm.CONCLUSIONS: Features of the Bravos afterloader system provide a robust and precise treatment delivery. All measurements were within manufacturer specifications. (C) 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Objective. Bioluminescence imaging (BLI) is a valuable tool for non-invasive monitoring of glioblastoma multiforme (GBM) tumor-bearing small animals without incurring x-ray radiation burden. However, the use of this imaging modality is limited due to photon scattering and lack of spatial information. Attempts at reconstructing bioluminescence tomography (BLT) using mathematical models of light propagation show limited progress. Approach. This paper employed a different approach by using a deep convolutional neural network (CNN) to predict the tumor's center of mass (CoM). Transfer-learning with a sizeable artificial database is employed to facilitate the training process for, the much smaller, target database including Monte Carlo (MC) simulations of real orthotopic glioblastoma models. Predicted CoM was then used to estimate a BLI-based planning target volume (bPTV), by using the CoM as the center of a sphere, encompassing the tumor. The volume of the encompassing target sphere was estimated based on the total number of photons reaching the skin surface. Main results. Results show sub-millimeter accuracy for CoM prediction with a median error of 0.59 mm. The proposed method also provides promising performance for BLI-based tumor targeting with on average 94% of the tumor inside the bPTV while keeping the average healthy tissue coverage below 10%. Significance. This work introduced a framework for developing and using a CNN for targeted radiation studies for GBM based on BLI. The framework will enable biologists to use BLI as their main image-guidance tool to target GBM tumors in rat models, avoiding delivery of high x-ray imaging dose to the animals. The authors would like to thank Dr Brent van der Heyden for fruitful discussion. This work was partially supported by special research fund for double doctorate degree projects in the framework of the cooperation between Hasselt university and Maastricht UMC + (Grant No. BOF17DOCMA13).

Brachytherapy has an excellent clinical outcome for different treatment sites. However, in vivo treatment verification is not performed in the majority of hospitals due to the lack of proper monitoring systems. This study investigates the use of an imaging panel (IP) and the photons emitted by a high dose rate (HDR) Ir-192 source to track source motion and obtain some information related to the patient anatomy. The feasibility of this approach was studied by monitoring the treatment delivery to a 3D printed phantom that mimicks a prostate patient. A 3D printed phantom was designed with a template for needle insertion, a cavity ('rectum') to insert an ultrasound probe, and lateral cavities used to place tissue-equivalent materials. CT images were acquired to create HDR Ir-192 treatment plans with a range of dwell times, interdwell distances and needle arrangements. Treatment delivery was verified with an IP placed at several positions around the phantom using radiopaque markers on the outer surface to register acquired IP images with the planning CT. All dwell positions were identified using acquisition times = 9 fps). Interdwell distances and dwell positions (in relation to the IP) were verified with accuracy better than 0.1 cm. Radiopaque markers were visible in the acquired images and could be used for registration with CT images. Uncertainties for image registration (IP and planning CT) between 0.1 and 0.4 cm. The IP is sensitive to tissue-mimicking insert composition and showed phantom boundaries that could be used to improve treatment verification. The IP provided sufficient time and spatial resolution for real-time source tracking and allows for the registration of the planning CT and IP images. The results obtained in this study indicate that several treatment errors could be detected including swapped catheters, incorrect dwell times and dwell positions. This project was partially supported by Varian Medical Systems. We thank Stavroula Giannuli and Rebecca Park from Varian for commenting on the paper. G P Fonseca and T van Wagenberg were supported by KWF (Grant 12780-Bas Mulder award). We thank Vera Schroen, Janneke Cruts and Esther Visser for their contribution to this project. Fonseca, GP (corresponding author), Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Radiat Oncol MAASTRO, Med Ctr, Doctor Tanslaan 12, NL-6229 ET Maastricht, Netherlands. gabriel.paivafonseca@maastro.nl

TOPAS MC software was used to model the efficiency of a coaxial p-type HPGe detector, type GX9023 from Canberra. The model was validated by comparing experimental efficiencies with efficiencies calculated by TOPAS MC simulations. Three different geometries of radionuclide sources, placed at different heights from the detector endcap, were used to validate the model. The imposed criteria of 5% relative difference was met for a range of radionuclides and gamma-ray energies. As a result, the created detector model with TOPAS MC was considered validated. The research was conducted under a PhD grant at Hasselt University. This work also received support from the open access scheme EUFRAT at the European Commission’s Joint Research Centre in Geel, Belgium. The author would also like to thank the developer team of TOPAS MC for the special licence allowing the use of TOPAS MC for gamma-ray spec-trometry applications

Glioblastoma multiforme (GBM) is a common and aggressive malignant brain cancer with a mean survival time of approximately 15 months after initial diagnosis. Currently, the standard-of-care (SOC) treatment for this disease consists of radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ). We sought to develop an orthotopic preclinical model of GBM and to optimize a protocol for non-invasive monitoring of tumor growth, allowing for determination of the efficacy of SOC therapy using a targeted RT strategy combined with TMZ. A strong correlation (r = 0.80) was observed between contrast-enhanced (CE)-CT-based volume quantification and bioluminescent (BLI)-integrated image intensity when monitoring tumor growth, allowing for BLI imaging as a substitute for CE-CT. An optimized parallel-opposed single-angle RT beam plan delivered on average 96% of the expected RT dose (20, 30 or 60 Gy) to the tumor. Normal tissue on the ipsilateral and contralateral sides of the brain were spared 84% and 99% of the expected dose, respectively. An increase in median survival time was demonstrated for all SOC regimens compared to untreated controls (average 5.2 days, p &lt, 0.05), but treatment was not curative, suggesting the need for novel treatment options to increase therapeutic efficacy.

A microdosimetric characterization of the 62 MeV proton beam line of CATANA has been performed all along the Spread Out Bragg Peak with three different detectors. Two silicon detectors and a Tissue Equivalent Proportional Counter measured at approximately the same depths of the SOBP. The TEPC is a new miniaturized gas counter developed at the Legnaro National Laboratories of INFN, modified to work without gas flow. The first silicon detector has been developed at the Politecnico of Milano and it is a monolithic telescope composed by a matrix of 2 µm thick cylindrical diodes with a diameter 9 µm. that compose the ΔE layer. The E and ΔE layers are fabricated on a single substrate of silicon. The third detector is the MicroPlus probe developed at the CMRP - University of Wollongong, it is an array of 3D sensitive volumes each with dimension 30x30 µm and 10 µm thick fabricated on SOI. Measurements performed with the three detectors are presented and discussed. This work was supported by the 5th Scientific Commission of the Italian Institute for Nuclear Physics (INFN), the Belgian Nuclear Research Centre SCK•CEN and Hasselt University. This work has been partially supported by the ENEN+ project that has received funding from the EURATOM research and training Work Programme 2016 – 2017 – 1 #755576.

Research on the applications of microdosimetry to particle therapy is spreading worldwide with a rapid increase of publications in the last years. In order to be able to perform an intercomparison of data acquired with different detectors in different clinical centres it is important to analyse data with a standard procedure. Often microdosimetric spectra are presented with different lower detection thresholds, in relation with different detection sensitivity and noise levels. The purpose of this paper is to analyse the influence of the lower detection threshold on the dose-mean lineal energy values, which are used as an assessment of the average LET of the radiation field. Furthermore, the dose distribution of the lineal energy can be used in combination with biological weighting functions to estimate the biological RBE at different positions along the penetration depths of therapeutic proton or carbon ion beams. Microdosimetric spectra cut at different lower thresholds lead in principle to different RBE values. It was an additional purpose of this work to analyse and discuss this effect both for proton and carbon ion irradiations. Spectra in proton and carbon ion beams gathered with a miniaturized TEPC developed at the Legnaro National Laboratories of the Italian Institute for Nuclear Physics (LNL-INFN) have been used to perform this study. Linear extrapolation of the microdosimetric spectra to a common value of 0.01 keV/μm significantly reduces the deviations in the mean values due to different lower thresholds. It is advisable to perform this procedure to have uniformity in data analysis and facilitate the intercomparison of data.

Dose escalation yields higher complete response to rectal tumors, which may enable the omission of surgery. Dose escalation using 50 kVp contact x-ray brachytherapy (CXB) allow the treatment of a selective volume, resulting in low toxicity and organs-at-risk preservation. However, the use of CXB devices is limited because of its high cost and lack of treatment planning tools. Hence, the MAASTRO applicator (for HDRA cylindrical applicator with lateral shielding was designed to be used with a rectoscope using its tip as treatment surface. Both the applicator and the rectoscope have a slanted edge to potentially allow easier placement against tumors. The applicator design was achieved by Monte Carlo modeling and validated experimentally with film dosimetry, using the Papillon 50 (P50) device as reference.The applicator delivers CXB doses in less than 9 min using a 20375 U source for a treatment area of approximately 20 × 20 mmThe MAASTRO applicator was designed to use HDR

Purpose The possibility to calibrate microdosimetric spectra using the proton- and electron-edge was proposed many years ago. It consists of two steps: first identifying the edge and a marker point on it and then ascribing the correct lineal energy value to the position of the edge in the event size spectrum. The purpose of this work is to study rigorously the marker identification for the proton-edge in the mini-TEPC spectra measured in neutron and in clinical proton fields, and the correspondent lineal energy value to assign to it. Materials and methods Microdosimetric measurements were performed with a cylindrical miniaturized tissue-equivalent proportional-counter (mini-TEPC) in neutron and gamma rays radiation fields at the CN accelerator of the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (LNL-INFN) and in the clinical 62 MeV proton beam of the Southern National Laboratories of INFN (LNS-INFN). The fitting of the proton-edge region of the microdosimetric spectra with a Fermi-like function was studied in both neutron and proton fields to identify the most precise marker point. The lineal energy value to ascribe to it was determined starting from the maximum energy deposit in protons obtained in FLUKA simulations. Results Both in neutron radiation field and in clinical proton beams the flex and the intercept of the tangent through the inflection point are determined with similar precision. The flex was chosen as the most suitable marker of the proton-edge in sealed detectors because it is known to be less sensitive to pressure variations. The lineal energy value to ascribe to the flex position for 0.75 μm of propane depends on the irradiation geometry: 194 keV/μm for isotropic radiation fields and 165 keV/μm for mono-directional radiation fields orthogonal to the axis of the cylinder. The calibration values for the proton-edge have been converted in water by means of the mean stopping power ratio of water and propane for protons obtaining 171 keV/μm for isotropic radiation fields and 145 keV/μm for mono-directional radiation fields.

Electronic brachytherapy sources use low energy photons to treat the tumor bed during or after breast-conserving surgery. The relative biological effectiveness of two electronic brachytherapy sources was explored to determine if spectral differences due to source design influenced radiation quality and if radiation quality decreased with distance in the breast. The RBE was calculated through the number of DNA double strand breaks (RBEDSB) using the Monte Carlo damage simulator (MCDS) in combination with other Monte Carlo electron/photon spectrum calculations. 50kVp photons from the Intrabeam (Carl Zeiss Surgical) and Axxent (Xoft) through 40-mm spherical applicators were simulated to account for applicator and tissue attenuation in a variety of breast tissue compositions. 40kVp Axxent photons were also simulated. Secondary electrons (known to be responsible for most DNA damage) spectra at different distance were inputted into MCDS to calculate the RBEDSB. All RBEDSB used a cobalt-60 reference. RBEDSB data was combined with corresponding average photon spectrum energy for the Axxent and applied to model-based average photon energy distributions to produce an RBEDSB map of an accelerated partial breast irradiation (APBI) patient. Both Axxent and Intrabeam 50kVp spectra were shown to have a comparable RBEDSB of between 1.4 and 1.6 at all distances in spite of progressive beam hardening. The Axxent 40kVp also demonstrated a similar RBEDSB at distances. Most RBEDSB variability was dependent on the tissue type as was seen in rib (RBEDSB approximate to 1.4), gland (approximate to 1.55), adipose (approximate to 1.59), skin (approximate to 1.52) and lung (approximate to 1.50). RBEDSB variability between both sources was within 2%. A correlation was shown between RBEDSB and average photon energy and used to produce an RBEDSB map of a dose distribution in an APBI patient dataset. Radiation quality is very similar between electronic brachytherapy sources studied. No significant reductions in RBEDSB were observed with increasing distance from the source.

A sealed miniaturized Tissue Equivalent Proportional Counter (mini-TEPC) able to work in gas-steady modality was developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL – INFN, Legnaro, Italy). The aim of the present work is to compare the response of this mini-TEPC with that of a silicon microdosimeter based on a monolithic telescope. Pairwise measurements were performed at the 62 MeV proton clinical Spread Out Bragg Peak (SOBP) of CATANA at the Southern National Laboratories of INFN (LNS – INFN, Catania, Italy). The dose mean lineal energy values were derived from the spectra measured with the two detectors and compared with the total dose-averaged LET calculated by means of Geant4 Monte Carlo simulations. Finally, the possibility to apply the Microdosimetric Kinetic Model (MKM) to reproduce RBE variations with depth along the Spread Out Bragg Peak was investigated.

PURPOSE: Dose escalation to rectal tumors leads to higher complete response rates and may thereby enable omission of surgery. Important advantages of endoluminal boosting techniques include the possibility to apply a more selective/localized boost than using external beam radiotherapy. A novel brachytherapy (BT) rectal applicator with lateral shielding was designed to be used with a rectoscope for eye-guided positioning to deliver a dose distribution similar to the one of contact x-ray radiotherapy devices, using commonly available high-dose-rate Ir-192 BT sources.METHODS AND MATERIALS: A cylindrical multichannel BT applicator with lateral shielding was designed by Monte Carlo modeling, validated experimentally with film dosimetry and compared with results found in the literature for the Papillon 50 (P50) contact x-ray radiotherapy device regarding rectoscope dimensions, radiation beam shape, dose fall-off, and treatment time.RESULTS: The multichannel applicator designed is able to deliver 30 Gy under 13 min with a 20350 U (5 Ci) source. The use of multiple channels and lateral shielding provide a uniform circular treatment surface with 22 mm in diameter. The resulting dose fall-off is slightly steeper (maximum difference of 5%) than the one generated by the P50 device with the 22 mm applicator.CONCLUSIONS: A novel multichannel rectal applicator for contact radiotherapy with high-dose-rate Ir-192 sources that can be integrated with commercially available treatment planning systems was designed to produce a dose distribution similar to the one obtained by the P50 device. (C) 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Purpose: The dose delivered with a HDR 192Ir afterloader can be separated into a dwell component, and a transit component resulting from the source movement. The transit component is directly dependent on the source speed profile and it is the goal of this study to measure accurate source speed profiles. Methods: A high speed video camera was used to record the movement of a 192 Ir source (Nucletron, an Elekta company, Stockholm, Sweden) for interdwell distances of 0.25–5 cm with dwell times of 0.1, 1, and 2 s. Transit dose distributions were calculated using a Monte Carlo code simulating the source movement. Results: The source stops at each dwell position oscillating around the desired position for a duration up to (0.026 ± 0.005) s. The source speed profile shows variations between 0 and 81 cm/s with average speed of ∼33 cm/s for most of the interdwell distances. The source stops for up to (0.005 ± 0.001) s at nonprogrammed positions in between two programmed dwell positions. The dwell time correction applied by the manufacturer compensates the transit dose between the dwell positions leading to a maximum overdose of 41 mGy for the considered cases and assuming an air-kerma strength of 48 000 U. The transit dose component is not uniformly distributed leading to over and underdoses, which is within 1.4% for commonly prescribed doses (3–10 Gy). Conclusions: The source maintains its speed even for the short interdwell distances. Dose variations due to the transit dose component are much lower than the prescribed treatment doses for brachytherapy, although transit dose component should be evaluated individually for clinical cases.

Brachytherapy is employed to treat a wide variety of cancers. However, an accurate treatment verification method is currently not available. This study describes a pre-treatment verification system that uses an imaging panel (IP) to verify important aspects of the treatment plan.A detailed modelling of the IP was only possible with an extensive calibration performed using a robotic arm. Irradiations were performed with a high dose rate (HDR) Ir-192 source within a water phantom. An empirical fit was applied to measure the distance between the source and the detector so 3D Cartesian coordinates of the dwell positions can be obtained using a single panel. The IP acquires 7.14 fps to verify the dwell times, dwell positions and air kerma strength (Sk). A gynecological applicator was used to create a treatment plan that was registered with a CT image of the water phantom used during the experiments for verification purposes. Errors (shifts, exchanged connections and wrong dwell times) were simulated to verify the proposed verification system.Cartesian source positions (panel measurement plane) have a standard deviation of about 0.02 cm. The measured distance between the source and the panel (z-coordinate) have a standard deviation up to 0.16 cm and maximum absolute error of approximate to 0.6 cm if the signal is close to sensitive limit of the panel. The average response of the panel is very linear with Sk. Therefore, Sk measurements can be performed with relatively small errors. The measured dwell times show a maximum error of 0.2 s which is consistent with the acquisition rate of the panel. All simulated errors were clearly identified by the proposed system.The use of IPs is not common in brachytherapy, however, it provides considerable advantages. It was demonstrated that the IP can accurately measure Sk, dwell times and dwell positions.

Purposes: This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed‐125 and the 6711 model seed. Materials & Methods: Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post‐implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG‐43 approximation effects were studied for a prostate and breast post‐implant. Results and Discussion: The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post‐implant studies, a 10% difference between MC calculations and the TG‐43 is found for both models of seeds. Conclusion: This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post‐implant treatments.

Brachytherapy treatment planning systems that use model-based dose calculation algorithms employ a more accurate approach that replaces the TG43-U1 water dose formalism and adopt the TG-186 recommendations regarding composition and geometry of patients and other relevant effects. However, no recommendations were provided on the transit dose due to the source traveling inside the patient. This study describes a methodology to calculate the transit dose using information from the treatment planning system (TPS) and considering the source's instantaneous and average speed for two prostate and two gynecological cases. The trajectory of the 192Ir HDR source was defined by importing applicator contour points and dwell positions from the TPS. The transit dose distribution was calculated using the maximum speed, the average speed and uniform accelerations obtained from the literature to obtain an approximate continuous source distribution simulated with a Monte Carlo code. The transit component can be negligible or significant depending on the speed profile adopted, which is not clearly reported in the literature. The significance of the transit dose can also be due to the treatment modality; in our study interstitial treatments exhibited the largest effects. Considering the worst case scenario the transit dose can reach 3% of the prescribed dose in a gynecological case with four catheters and up to 11.1% when comparing the average prostate dose for a case with 16 catheters. The transit dose component increases by increasing the number of catheters used for HDR brachytherapy, reducing the total dwell time per catheter or increasing the number of dwell positions with low dwell times. This contribution may become significant (>5%) if it is not corrected appropriately. The transit dose cannot be completely compensated using simple dwell time corrections since it may have a non-uniform distribution. An accurate measurement of the source acceleration and maximum speed should be incorporated in clinical practice or provided by the manufacturer to determine the transit dose component with high accuracy.

Purpose Brachytherapy dose calculation is commonly performed using the Task Group-No 43 Report-Updated protocol (TG-43U1) formalism. Recently, a more accurate approach has been proposed that can handle tissue composition, tissue density, body shape, applicator geometry, and dose reporting either in media or water. Some model-based dose calculation algorithms are based on Monte Carlo (MC) simulations. This work presents a software platform capable of processing medical images and treatment plans, and preparing the required input data for MC simulations. Methods and Materials The A Medical Image-based Graphical platfOrm—Brachytherapy module (AMIGOBrachy) is a user interface, coupled to the MCNP6 MC code, for absorbed dose calculations. The AMIGOBrachy was first validated in water for a high-dose-rate 192Ir source. Next, dose distributions were validated in uniform phantoms consisting of different materials. Finally, dose distributions were obtained in patient geometries. Results were compared against a treatment planning system including a linear Boltzmann transport equation (LBTE) solver capable of handling nonwater heterogeneities. Results The TG-43U1 source parameters are in good agreement with literature with more than 90% of anisotropy values within 1%. No significant dependence on the tissue composition was observed comparing MC results against an LBTE solver. Clinical cases showed differences up to 25%, when comparing MC results against TG-43U1. About 92% of the voxels exhibited dose differences lower than 2% when comparing MC results against an LBTE solver. Conclusion The AMIGOBrachy can improve the accuracy of the TG-43U1 dose calculation by using a more accurate MC dose calculation algorithm. The AMIGOBrachy can be incorporated in clinical practice via a user-friendly graphical interface.

Purpose Catheters made of either metal or plastic are currently used in brachytherapy treatment to insert radiative sources into patients. However, the radiation dose perturbations due to catheter attenuation are not taken into account in treatment planning. The purpose of this work is to quantify the effects of catheter composition on dose distribution and study their impacts on the overall treatment with high-dose-rate 192Ir sources. Methods and Materials Dose perturbations are first studied in a simplified case consisting of two parallel catheters. The catheter wall is either composed of stainless steel or polyoxymethylene. The attenuations are studied as the distance between the two catheters is varied from 5 to 30 mm. Dose perturbations resulting from irradiation are evaluated with a Monte Carlo GEANT4 dose calculation algorithm. The dose differences are further investigated with seven typical high-dose-rate prostate treatment plans involving 17 catheters. Results The dose differences compared with water in the simplified case reach −4.3 ± 0.1% for stainless steel and 1.7 ± 0.5% for polyoxymethylene at 10 mm above the source when the catheters are separated by a distance of 5 mm. Dose perturbations are reduced in real treatment plans because of the contributions of the many dwell positions. Stainless steel and polyoxymethylene catheters induce on an average a dose difference of −1.3 ± 0.3% and 0.1 ± 0.2%, respectively in the target. Conclusions The dose differences reported in this work do not warrant any changes in the clinical procedures.

Background and purpose To compare MRI-guided treatment planning approaches between four centres that use tandem-ovoid applicators. Material and methods Four centres generated three treatment plans for four patients: standard, optimised intracavitary, and optimised intracavitary/interstitial. Prescribed D90 High-Risk CTV (HR-CTV) was 85Gy EQD2 (external-beam radiotherapy and brachytherapy), while the D 2cc OAR limit was 90Gy EQD2 for bladder and 75Gy EQD2 for rectum, sigmoid, and bowel, respectively. DVH-parameters, source loading patterns and spatial dose distributions of the three treatment plans were compared. Results The standard plans of the different centres were comparable with respect to the D90 HR-CTV, but differed in OAR doses. MRI-guided intracavitary optimisation resulted in organ sparing and smaller variation in DVH parameters between the centres. Adding interstitial needles led to target dose escalation while respecting the OAR constraints. However, substantial differences in relative weights of the applicator parts resulted in an increased variation in DVH parameters and locations of high dose regions. Conclusions MRI-guided brachytherapy treatment planning optimisation provides the possibility to increase the dose to the HR-CTV and spare the OARs. Depending on the degree of conformity the centres make different choices in relative weighting of applicator parts, leading to different dose distributions.

In vivo validation of models of DNA damage repair will enable their use for optimizing clinical radiotherapy. In this study, a theoretical assessment was made of DNA double-strand break (DSB) induction in normal breast tissue after intraoperative radiation therapy (IORT), which is now an accepted form of adjuvant radiotherapy for selected patients with early breast cancer. DSB rates and relative biological effectiveness (RBE) were calculated as a function of dose, radiation quality and dose rate, each varying based on the applicator size used during IORT. The spectra of primary electrons in breast tissue adjacent to each applicator were calculated using measured X-ray spectra and Monte Carlo methods, and were used to inform a Monte Carlo damage simulation code. In the absence of repair, asymptotic RBE values (relative to (60)Co) were approximately 1.5. Beam-quality changes led to only minor variations in RBE among applicators, though differences in dose rate and overall dose delivery time led to larger variations and a rapid decrease in RBE. An experimental assessment of DSB induction was performed ex vivo using pre- and postirradiation tissue samples from patients receiving breast intraoperative radiation therapy. Relative DSB rates were assessed via ?-H2AX immunohistochemistry using proportional staining. Maximum-likelihood parameter estimation yielded a DSB repair halftime of 25.9 min (95% CI, 21.5-30.4 min), although the resulting model was not statistically distinguishable from one where there was no change in DSB yield among patients. Although the model yielded an in vivo repair halftime of the order of previous estimates for in vitro repair halftimes, we cannot conclude that it is valid in this context. This study highlights some of the uncertainties inherent in population analysis of ex vivo samples, and of the quantitative limitations of immunohistochemistry for assessment of DSB repair.

Purpose For gynecological treatments, it is standard to acquire CT images and preferably also MR images before each treatment to calculate the dose of the day. The dose of the complete treatment is calculated by adding the dose metrics of each fraction. It makes the conservative assumption that the same part of the organs at risk always receives the highest dose. The dose calculated this way often limits the prescription dose or the target coverage. We investigated the use of deformable image registration (DIR) as an alternative method to assess the cumulative dose for a treatment course. Methods and materials Rigid registration is preformed on CT images, followed by DIR. DIR can be based either solely on the three-dimensional images or combined with organ contours. To improve DIR in the pelvic region with low CT contrast, we propose (1) using contours drawn on CT or (2) modifying artificially the contrast in certain volumes. The dose matrix from fraction_n (n > 1) is deformed using a calculated deformation field. Results The use of the contrast-enhanced images or of contour information helps to guide the DIR. However, because of the very high dose gradients involved in brachytherapy, the uncertainty on the accumulated dose remains of the order of 5–10%. Even for good contour matching, a small local error in the deformation can have significant consequences for the dose distribution. Conclusions Using DIR, based on image features and contours, allows to accumulate the dose from different brachytherapy fractions. A robust validation procedure should be developed.

Purpose: In gynecological radiotherapy with high dose rate (HDR){sup 192}Ir brachytherapy, the treatment complexity has increased due to improved optimization techniques and dose constraints. As a consequence, it has become more important to verify the dose delivery to the target and also to the organs at risk (e.g., the bladder). In vivo dosimetry, where dosimeters are placed in or on the patient, is one way of verifying the dose but until recently this was hampered by motion of the radiation detectors with respect to the source. The authors present a novel dosimetry method using a position sensitive radiation detector. Methods: The prototype RADPOS system (Best Medical Canada) consists of a metal oxide field effect transistor (MOSFET) dosimeter coupled to a position-sensor, which deduces its 3D position in a magnetic field. To assess the feasibility of in vivo dosimetry based on the RADPOS system, different characteristics of the detector need to be investigated. Using a PMMA phantom, the positioning accuracy of the RADPOS system was quantified by comparing position readouts with the known position of the detector along the x and y-axes. RADPOS dose measurements were performed at various distances from a Nucletron{sup 192}Ir source in a PMMA phantom to evaluatemore » the energy dependence of the MOSFET. A sensitivity analysis was performed by calculating the dose after varying (1) the position of the RADPOS detector to simulate organ motion and (2) the position of the first dwell position to simulate errors in delivery. The authors also performed an uncertainty analysis to determine the action level (AL) that should be used during in vivo dosimetry. Results: Positioning accuracy is found to be within 1 mm in the 1-10 cm range from the origin along the x-axis (away from the transmitter), meeting the requirements for in vivo dosimetry. Similar results are obtained for the other axes. The ALs are chosen to take into account the total uncertainty on the measurements. As a consequence for in vivo dosimetry, it is determined that the RADPOS sensor, if placed, for example, in the bladder Foley balloon, would detect a 2 mm motion of the bladder, at a 5% chance of a false positive, with an AL limit of 9% of the dose delivered. The authors found that source position errors, caused by, e.g., a wrong first dwell position, are more difficult to detect; indeed, with our single RADPOS detector, positioned in the bladder, dwell position errors below 5 mm and resulting in a dose error within 10%, could be detected in the tandem but not in the colpostats. A possible solution to improve error detection is to use multiple MOSFETs to obtain multiple dose values. Conclusions: In this study, the authors proposed a dosimetry procedure, based on the novel RADPOS system, to accurately determine the position of the radiation dosimeter with respect to the applicator. The authors found that it is possible to monitor the delivered dose in a point and compare it to the predetermined dose. This allows in principle the detection of problems such as bladder motion/filling or source mispositioning. Further clinical investigation is warranted.« less

PURPOSE The dosimetric impact of gold fiducial markers (FM) implanted prior to external beam radiotherapy of prostate cancer on low dose rate (LDR) brachytherapy seed implants performed in the context of combined therapy was investigated. METHODS A virtual water phantom was designed containing a single FM. Single and multi source scenarios were investigated by performing Monte Carlo dose calculations, along with the influence of varying orientation and distance of the FM with respect to the sources. Three prostate cancer patients treated with LDR brachytherapy for a recurrence following external beam radiotherapy with implanted FM were studied as surrogate cases to combined therapy. FM and brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose calculations were performed with and without FM. The dosimetric impact of the FM was evaluated by quantifying the amplitude of dose shadows and the volume of cold spots. D(90) was reported based on the post implant CT prostate contour. RESULTS Large shadows are observed in the single source-FM scenarios. As expected from geometric considerations, the shadows are dependent on source-FM distance and orientation. Large dose reductions are observed at the distal side of FM, while at the proximal side a dose enhancement is observed. In multisource scenarios, the importance of shadows appears mitigated, although FM at the periphery of the seed distribution caused underdosage (

Brachytherapy is associated with highly heterogeneous spatial dose distributions. This heterogeneity is usually ignored when estimating the biological effective dose (BED). In addition, the heterogeneities of the medium including the tissue heterogeneity (TH) and the interseed attenuation (ISA) are also contributing to the heterogeneity of the dose distribution, but they are both ignored in Task Group 43 (TG43)-based protocols. This study investigates the effect of dose heterogeneity, TH and ISA on metrics that are commonly used to quantify biological efficiency in brachytherapy. The special case of 29 breast cancer patients treated with permanent Pd-103 seed implant is considered here. BED is compared to equivalent uniform BED (EUBED) capable of considering the spatial heterogeneity of the dose distribution. The effects of TH and ISA on biological efficiency of treatments are taken into account by comparing TG43 with Monte Carlo (MC) dose calculations for each patient. The effect of clonogenic repopulation is also considered. The analysis is performed for different sets of (alpha/beta,alpha) ratios of (2, 0.3), (4, 0.27) and (10, 0.3) [Gy, Gy(-1)] covering the whole range of reported alpha/beta values in the literature. BED is sometimes larger and sometimes smaller than EUBED(TG43) indicating that the effect of the dose heterogeneity is not similar among patients. The effect of the dose heterogeneity can be characterized by using the D-99 dose metric. For each set of the radiobiological parameters considered, a D-99 threshold is found over which dose heterogeneity will cause an overestimation of the biological efficiencies while the inverse happens for smaller D-99 values. EUBED(MC) is always larger than EUBED(TG43) indicating that by neglecting TH and ISA in TG43-based dosimetry algorithms, the biological efficiencies may be underestimated by about 10 Gy. Overall, by going from BED to the more accurate EUBED(MC) there is a gain of about 9.6 to 13 Gy on the biological efficiency. The efficiency gain is about 10.8 to 14 Gy when the repopulation is considered. Dose heterogeneity does not have a constant impact on the biological efficiencies and may under- or overestimate the efficacy in different patients. However, the combined effect of neglecting dose heterogeneity, TH and ISA results in underestimation of the biological efficiencies in permanent breast seed implants.