Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios.

BACKGROUND AND PURPOSE: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways. MATERIAL AND METHODS: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/ß values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. RESULTS: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases. CONCLUSION: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

Monte Carlo calculation of the TG-43 dosimetry parameters for the INTRABEAM source with spherical applicators.

OBJECTIVE: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarezet al(2020Phys. Med. Biol.65245041). The current study focuses on the dosimetry characterization of the INTRABEAM source with the eight available spherical applicators according to the TG-43 formalism using Monte Carlo (MC) simulations. APPROACH: This report includes the calculated dose-rate conversion coefficients that determine the absolute dose rate to water at a reference point of 10 mm from the applicator surface, based on calibration air-kerma rate measurements at 50 cm from the source on its transverse plane. Since the air-kerma rate measurements are not yet provided from a standards laboratory for the INTRABEAM, the values in the present study were calculated with MC. This approach is aligned with other works in the search for standardization of the dosimetry of electronic brachytherapy sources. As a validation of the MC model, depth dose calculations along the source axis were compared with calibration data from the source manufacturer. MAIN RESULTS: The calculated dose-rate conversion coefficients were 434.0 for the bare probe, and 683.5, 548.3, 449.9, 376.5, 251.0, 225.6, 202.8, and 182.6 for the source with applicators of increasing diameter from 15 to 50 mm, respectively. The radial dose and the 2D anisotropy functions of the TG-43 formalism were also obtained and tabulated in this document. SIGNIFICANCE: This work presents the data required by a treatment planning system for the characterization of the INTRABEAM system in the context of intraoperative radiotherapy applications.

Clinical Implication of Dosimetry Formalisms for Electronic Low-Energy Photon Intraoperative Radiation Therapy.

PURPOSE: Intraoperative radiation therapy (IORT) using the INTRABEAM, a miniature x-ray source, has shown to be effective in treating breast cancer. However, recent investigations have suggested a significant deviation between the reported and delivered doses. In this work, the dose delivered by INTRABEAM in the TARGIT breast protocol was investigated, along with the dose from the Xoft Axxent, another source used in breast IORT. METHODS AND MATERIALS: The absorbed dose from the INTRABEAM was determined from ionization chamber measurements using: (a) the manufacturer-recommended formula (Zeiss V4.0 method), (b) a Monte Carlo calculated chamber conversion factor (CQ method), and (c) the formula consistent with the TARGIT breast protocol (TARGIT method). The dose from the Xoft Axxent was determined from ionization chamber measurements using the Zeiss V4.0 method and calculated using the American Association of Physicists in Medicine TG-43 formalism. RESULTS: For a nominal TARGIT prescription of 20 Gy, the dose at the INTRABEAM applicator surface ranged from 25.2 to 31.7 Gy according to the CQ method for the largest (5 cm) and smallest (1.5 cm) diameter applicator, respectively. The Zeiss V4.0 method results were 7% to 10% lower (23.2 to 28.6 Gy). At 1 cm depth, the CQ and Zeiss V4.0 absorbed doses were also larger than those predicted by the TARGIT method. The dose at 1 cm depth from the Xoft Axxent for a surface dose of 20 Gy was slightly less than INTRABEAM (3%-7% compared with CQ method). An exception was for the 3 cm applicator, where the Xoft dose was appreciably lower (31%). CONCLUSIONS: The doses delivered in the TARGIT breast protocol with INTRABEAM were significantly greater than the prescribed 20 Gy and depended on the size of spherical applicator used. Breast IORT treatments with the Xoft Axxent received less dose compared with TARGIT INTRABEAM, which could have implications for studies comparing clinical outcomes between the 2 devices.

Monte Carlo calculation of the relative TG-43 dosimetry parameters for the INTRABEAM electronic brachytherapy source.

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source ([Formula: see text]10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides (192Ir, 125I and 103Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Dose measurements nearby low energy electronic brachytherapy sources using radiochromic film.

PURPOSE: We investigate the effect of the GafChromic™ film EBT3 model absorbed dose energy response when used for dose measurements around low-energy photon sources. Monte Carlo based correction procedure in synergy with appropriate calibration curves was shown to provide more accurate absorbed dose (either relative or absolute). An assessment was made of possible dose errors that might be encountered if such energy dependent response is ignored. METHODS: We measured PDDs in water from a Xoft 50 kVp source using EBT3 film, and compared to PDD measurements acquired with a PTW-TN34013 parallel-plate ionization chamber. For the x-ray source, we simulated spectra using the EGSnrc (BEAMnrc) Monte Carlo code, and calculated Half Value Layer (HVL) at different distances from the source in water. Measurement strips of EBT3 film were positioned at distances of 2-6 cm from the Xoft source in a water phantom using a custom-made holder and irradiated simultaneously. RESULTS: Our results show that film calibration curves obtained at beam qualities near the effective energy of the Xoft 50 kVp source in water lead to variation in absorbed dose energy dependence of the response of around 5%. However, if the calibration curve was established in an MV beam quality, the error in absorbed dose could be as large as 20%. CONCLUSION: Accurate dose measurements using radiochromic films at low photon energies require that the radiochromic film dosimetry system be calibrated at appropriate corresponding low energies, as large absorbed dose errors are expected when film calibration is performed in MV beam qualities.

Determination of absorbed dose to water from a miniature kilovoltage x-ray source using a parallel-plate ionization chamber.

Electronic brachytherapy sources are widely accepted as alternatives to radionuclide-based systems. Yet, formal dosimetry standards for these devices to independently complement the dose protocol provided by the manufacturer are lacking. This article presents a formalism for calculating and independently verifying the absorbed dose to water from a kV x-ray source (The INTRABEAM System) measured in a water phantom with an ionization chamber calibrated in terms of air-kerma. This formalism uses a Monte Carlo (MC) calculated chamber conversion factor, [Formula: see text], to convert air-kerma in a reference beam to absorbed dose to water in the measurement beam. In this work [Formula: see text] was determined for a PTW 34013 parallel-plate ionization chamber. Our results show that [Formula: see text] was sensitive to the chamber plate separation tolerance, with differences of up to 15%. [Formula: see text] was also found to have a depth dependence which varied with chamber plate separation (0 to 10% variation for the smallest and largest cavity height, over 3 to 30 mm depth). However for all chamber dimensions investigated, [Formula: see text] was found to be significantly larger than the manufacturer reported value, suggesting that the manufacturer recommended method of dose calculation could be underestimating the dose to water.

A global pharmaceutical company initiative: an evidence-based approach to define the upper limit of body weight loss in short term toxicity studies.

Short term toxicity studies are conducted in animals to provide information on major adverse effects typically at the maximum tolerated dose (MTD). Such studies are important from a scientific and ethical perspective as they are used to make decisions on progression of potential candidate drugs, and to set dose levels for subsequent regulatory studies. The MTD is usually determined by parameters such as clinical signs, reductions in body weight and food consumption. However, these assessments are often subjective and there are no published criteria to guide the selection of an appropriate MTD. Even where an objective measurement exists, such as body weight loss (BWL), there is no agreement on what level constitutes an MTD. A global initiative including 15 companies, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), has shared data on BWL in toxicity studies to assess the impact on the animal and the study outcome. Information on 151 studies has been used to develop an alert/warning system for BWL in short term toxicity studies. The data analysis supports BWL limits for short term dosing (up to 7days) of 10% for rat and dog and 6% for non-human primates (NHPs).