Characterization of a commercial plastic scintillator for electron FLASH dosimetry.

PURPOSE: This study investigated the potential of a commercially available plastic scintillator, the Exradin W2, as a real-time dosimeter for ultra-high-dose-rate (UHDR) electron beams. This work aimed to characterize this system's performance under UHDR conditions and addressed limitations inherent to other conventional dosimetry systems. METHODS AND MATERIALS: We assessed the W2's performance as a UHDR electron dosimeter using a 16 MeV UHDR electron beam from the FLASH research extension (FLEX) system. Additionally, the vendor provided a beta firmware upgrade to better handle the processing of the high signal generated in the UHDR environment. We evaluated the W2 regarding dose-per-pulse, pulse repetition rate, charge versus distance, and pulse linearity. Absorbed dose measurements were compared against those from a plane-parallel ionization chamber, optically stimulated luminescent dosimeters and radiochromic film. RESULTS: We observed that the 1 × 1 mm W2 scintillator with the MAX SD was more suitable for UHDR dosimetry compared to the 1 × 3 mm W2 scintillator, capable of matching film measurements within 2% accuracy for dose-per-pulse up to 3.6 Gy/pulse. The W2 accurately ascertained the inverse square relationship regarding charge versus virtual source distance with R2 of ∼1.00 for all channels. Pulse linearity was accurately measured with the W2, demonstrating a proportional response to the delivered pulse number. There was no discernible impact on the measured charge of the W2 when switching between the available repetition rates of the FLEX system (18-180 pulses/s), solidifying consistent beam output across pulse frequencies. CONCLUSIONS: This study tested a commercial plastic scintillator detector in a UHDR electron beam, paving the way for its potential use as a real-time, patient-specific dosimetry tool for future FLASH radiotherapy treatments. Further research is warranted to test and improve the signal processing of the W2 dosimetry system to accurately measure in UHDR environments using exceedingly high dose-per-pulse and pulse numbers.

Alendronate-Modified Polymeric Micelles for the Treatment of Breast Cancer Bone Metastasis.

Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remains high in incidence and challenging to manage. Here, we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation, and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity, and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactant-based formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

VMAT and IMRT plan-specific correction factors for linac-based ionization chamber dosimetry.

PURPOSE: The determination of absorbed dose to water from external beam radiotherapy using radiation detectors is currently rooted in calibration protocols that do not account for modulations encountered in patient-specific deliveries. Detector response in composite clinical fields has not been extensively studied due to the time and effort required to determine these corrections on a case-by-case basis. To help bridge this gap in knowledge, corrections for the Exradin A1SL scanning chamber were determined in a large number of composite clinical fields using Monte Carlo methods. The chamber-specific perturbations that contribute the most to the overall correction factor were also determined. METHODS: A total of 131 patient deliveries comprised of 834 beams from a Varian C-arm linear accelerator were converted to EGSnrc Monte Carlo inputs. A validated BEAMnrc 21EX linear accelerator model was used as a particle source throughout the EGSnrc simulations. Composite field dose distributions were compared against a commercial treatment planning system for validation. The simulation geometry consisted of a cylindrically symmetric water-equivalent phantom with the Exradin A1SL scanning chamber embedded inside. Various chamber perturbation factors were investigated in the egs_chamber user code of EGSnrc and were compared to reference field conditions to determine the plan-specific correction factor. RESULTS: The simulation results indicated that the Exradin A1SL scanning chamber is suitable to use as an absolute dosimeter within a high-dose and low-gradient target region in most nonstandard composite fields; however, there are still individual cases that require larger delivery-specific corrections. The volume averaging and replacement perturbations showed the largest impact on the overall plan-specific correction factor for the Exradin A1SL scanning chamber, and both volumetric modulated arc therapy (VMAT) and step-and-shoot beams demonstrated similar correction factor magnitudes among the data investigated. Total correction magnitudes greater than 2% were required by 9.1% of step-and-shoot beams and 14.5% of VMAT beams. When examining full composite plan deliveries as opposed to individual beams, 0.0% of composite step-and-shoot plans and 2.6% of composite VMAT plans required correction magnitudes greater than 2%. CONCLUSIONS: The A1SL scanning chamber was found to be suitable to use for absolute dosimetry in high-dose and low-gradient dose regions of composite IMRT plans but even if a composite dose distribution is large compared to the detector used, a correction-free absorbed dose-to-water measurement is not guaranteed.

Ion recombination and polarity corrections for small-volume ionization chambers in high-dose-rate, flattening-filter-free pulsed photon beams.

PURPOSE: To investigate ion recombination and polarity effects in scanning and microionization chambers when used with digital electrometers and high-dose-rate linac beams such as flattening-filter-free (FFF) fields, and to compare results against conventional pulsed and continuous photon beams. METHODS: Saturation curves were obtained for one Farmer-type ionization chamber and eight small-volume chamber models with volumes ranging from 0.01 to 0.13 cm3 using a Varian TrueBeam™ STx with FFF capability. Three beam modes (6 MV, 6 MV FFF, and 10 MV FFF) were investigated, with nominal dose-per-pulse values of 0.0278, 0.0648, and 0.111 cGy/pulse, respectively, at dmax . Saturation curves obtained using the Theratronics T1000 60 Co unit at the UWADCL and a conventional linear accelerator (Varian Clinac iX) were used to establish baseline behavior. Jaffé plots were fitted to obtain Pion , accounting for exponential effects such as charge multiplication. These values were compared with the two-voltage technique recommended in TG-51, and were plotted as a function of dose-per-pulse to assess the ability of small-volume chambers to meet reference-class criteria in FFF beams. RESULTS: Jaffé- and two-voltage-determined Pion values measured for high-dose-rate beams agreed within 0.1% for the Farmer-type chamber and 1% for scanning and microionization chambers, with the exception of the CC01 which agreed within 2%. With respect to ion recombination and polarity effects, the Farmer-type chamber, scanning chambers and the Exradin A26 microchamber exhibited reference-class behavior in all beams investigated, with the exception of the IBA CC04 scanning chamber, which had an initial recombination correction that varied by 0.2% with polarity. All microchambers investigated, with the exception of the A26, exhibited anomalous polarity and ion recombination behaviors that make them unsuitable for reference dosimetry in conventional and high-dose-rate photon beams. CONCLUSIONS: The results of this work demonstrate that recombination and polarity behaviors seen in conventional pulsed and continuous photon beams trend accordingly in high-dose-rate FFF linac beams. Several models of small-volume ionization chambers used with a digital electrometer have been shown to meet reference-class requirements with respect to ion recombination and polarity, even in the high-dose-rate environment. For such chambers, a two-voltage technique agreed well with more rigorous methods of determining Pion . However, the results emphasize the need for careful reference detector selection, and indicate that ionization chambers ought to be extensively tested in each beam of interest prior to their use for reference dosimetry.