Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma.

PURPOSE: The intraoperative radiotherapy in newly diagnosed glioblastoma multiforme (INTRAGO) clinical trial assesses survival in patients with glioblastoma treated with intraoperative radiation therapy (IORT) using the INTRABEAM. Treatment planning for INTRABEAM relies on vendor-provided in-water depth dose curves obtained according to the TARGeted Intraoperative radioTherapy (TARGIT) dosimetry protocol. However, recent studies have shown discrepancies between the estimated TARGIT and delivered doses. This work evaluates the effect of the choice of dosimetry formalism on organs at risk (OAR) doses. METHODS AND MATERIALS: A treatment planning framework for INTRABEAM was developed to retrospectively calculate the IORT dose in 8 INTRAGO patients. These patients received an IORT prescription dose of 20 to 30 Gy in addition to external beam radiation therapy. The IORT dose was obtained using (1) the TARGIT method; (2) the manufacturer's V4.0 method; (3) the CQ method, which uses an ionization chamber Monte Carlo (MC) calculated factor; (4) MC dose-to-water; and (5) MC dose-to-tissue. The IORT dose was converted to 2 Gy fractions equivalent dose. RESULTS: According to the TARGIT method, the OAR dose constraints were respected in all cases. However, the other formalisms estimated a higher mean dose to OARs and revealed 1 case where the constraint for the brain stem was exceeded. The addition of the external beam radiation therapy and TARGIT IORT doses resulted in 10 cases of OARs exceeding the dose constraints. The more accurate MC calculation of dose-to-tissue led to the highest dosimetric differences, with 3, 3, 2, and 2 cases (out of 8) exceeding the dose constraint to the brain stem, optic chiasm, optic nerves, and lenses, respectively. Moreover, the mean cumulative dose to brain stem exceeded its constraint of 66 Gy with the MC dose-to-tissue method, which was not evident with the current INTRAGO clinical practice. CONCLUSIONS: The current clinical approach of calculating the IORT dose with the TARGIT method may considerably underestimate doses to nearby OARs. In practice, OAR dose constraints may have been exceeded, as revealed by more accurate methods.

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.

An investigation into the INTRABEAM miniature x-ray source dosimetry using ionization chamber and radiochromic film measurements.

PURPOSE: Intraoperative radiotherapy using The INTRABEAM System (Carl Zeiss Meditec AG, Jena, Germany), a miniature low-energy x-ray source, has proven to be an effective modality in the treatment of breast cancer. However, some uncertainties remain in its dosimetry. In this work, we investigated the INTRABEAM system dosimetry by performing ionization chamber and radiochromic film measurements of absorbed dose in a water phantom. METHODS: Ionization chamber measurements were performed with a PTW 34013 parallel-plate soft x-ray chamber at source to detector distances of 5 to 30 mm calculated using (a) the dose formula consistent with the TARGIT breast protocol (TARGIT), (b) the formula recommended by the manufacturer (Zeiss), and (c) the recently proposed CQ formalism of Watson et al. (Physics in Medicine & Biology, 2018;63:015016) EBT3 Gafchromic film measurements were made at the same depths in water. To account for the energy dependence of EBT3 film, multiple dose response calibration curves were employed across a range of photon beam qualities relevant to the INTRABEAM spectrum in water. RESULTS: At all depths investigated, the TARGIT dose was significantly lower than that measured by the Zeiss and CQ methods, as well as film. These dose differences ranged from 14% to as large as 80%. In general, the doses measured by film, and the Zeiss and CQ methods were in good agreement to within measurement uncertainties (5-6%). CONCLUSIONS: These results suggest that the TARGIT dose underestimates the physical dose to water from the INTRABEAM source. Understanding the correlation between the TARGIT and physical dose is important for any studies wishing to make dosimetric comparisons between the INTRABEAM and other radiation emitting devices.

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.

Technical Note: Effect of explicit M and N-shell atomic transitions on a low-energy x-ray source.

PURPOSE: In EGSnrc, atomic transitions to and from the M and N-shells are treated in an average way by default. This approach is justified in which the energy difference between explicit and average M and N-shell binding energies is less than 1 keV, and for most applications can be considered negligible. However, for simulations of low energy x-ray sources on thin, high-Z targets, characteristic x-rays can make up a significant portion of the source spectra. As of release V4-2.4.0, EGSnrc has included an option to enable a more complete algorithm of all atomic transitions available in the EADL compilation. In this paper, the effect of M and N-shell averaging on the calculation of half-value layer (HVL) and relative depth dose (RDD) curve of a 50 kVp intraoperative x-ray tube with a thin gold target was investigated. METHODS: A 50 kVp miniature x-ray source with a gold target (The INTRABEAM System, Carl Zeiss, Germany) was modeled with the EGSnrc user code cavity, both with and without M and N-shell averaging. From photon fluence spectra simulations, the source HVLs were determined analytically. The same source model was then used with egs_chamber to calculate RDD curves in water. RESULTS: A 4% increase of HVL was reported when accounting for explicit M and N-shell transitions, and up to a 9% decrease in local relative dose for normalization at 3 mm depth in water. CONCLUSIONS: The EGSnrc default of using averaged M and N-shell binding energies has an observable effect on the HVL and RDD of a low energy x-ray source with high-Z target. For accurate modeling of this class of devices, explicit atomic transitions should be included.

Implementation of an efficient Monte Carlo calculation for CBCT scatter correction: phantom study.

Cone-beam computed tomography (CBCT) images suffer from poor image quality, in a large part due to contamination from scattered X-rays. In this work, a Monte Carlo (MC)-based iterative scatter correction algorithm was implemented on measured phantom data acquired from a clinical on-board CBCT scanner. An efficient EGSnrc user code (egs_cbct) was used to transport photons through an uncorrected CBCT scan of a Catphan 600 phantom. From the simulation output, the contribution from primary and scattered photons was estimated in each projection image. From these estimates, an iterative scatter correction was performed on the raw CBCT projection data. The results of the scatter correction were compared with the default vendor reconstruction. The scatter correction was found to reduce the error in CT number for selected regions of interest, while improving contrast-to-noise ratio (CNR) by 18%. These results demonstrate the performance of the proposed scatter correction algorithm in improving image quality for clinical CBCT images.