Commissioning and initial validation of Eclipse eMC algorithm for the electron FLASH research extension (FLEX) system for pre-clinical studies.

PURPOSE: To investigate the feasibility of commissioning the 16 MeV electron FLASH Extension (FLEX) in the commercial treatment planning system (TPS) for biomedical research with cell and mouse models, and in silico treatment planning studies. METHODS: To commission the FLEX system with the electron Monte Carlo (eMC) algorithm in the commercial TPS, radiochromic film was used to measure the vendor-recommended beam data. Once the beam model was generated for the eMC algorithm, supplemental measurements were collected for validation purposes and compared against the TPS-calculated results. Additionally, the newly commissioned 16 MeV FLASH beam was compared to the corresponding 16 MeV conventional electron beam. RESULTS: The eMC algorithm effectively modeled the FLEX system. The eMC-calculated PDDs and profiles for the 16 MeV electron FLASH beam agreed with measured values within 1%, on average, for 6 × 6 cm2 and 10 × 10 cm2 applicators. Flatness and symmetry deviated by less than 1%, while FWHM and penumbra agreed within 1 mm for both eMC-calculated and measured profiles. Additionally, the small field (i.e., 2-cm diameter cutout) that was measured for validation purposes agreed with TPS-calculated results within 1%, on average, for both the PDD and profiles. The FLASH and conventional dose rate 16 MeV electron beam were in agreement in regard to energy, but the profiles for larger field sizes began to deviate (>10 × 10 cm2) due to the forward-peaked nature of the FLASH beam. For cell irradiation experiments, the measured and eMC-calculated in-plane and cross-plane absolute dose profiles agreed within 1%, on average. CONCLUSIONS: The FLEX system was successfully commissioned in the commercial TPS using the eMC algorithm, which accurately modeled the forward-peaked nature of the FLASH beam. A commissioned TPS for FLASH will be useful for pre-clinical cell and animal studies, as well as in silico FLASH treatment planning studies for future clinical implementation.

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.

Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.

PURPOSE: Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. METHODS: A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. RESULTS: The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. CONCLUSION: Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.

An evaluation of quality assurance guidelines comparing the American College of Radiology and American Association of Physicists in Medicine task group 284 for magnetic resonance simulation.

PURPOSE: The purpose of this study was to evaluate similarities and differences in quality assurance (QA) guidelines for a conventional diagnostic magnetic resonance (MR) system and a MR simulator (MR-SIM) system used for radiotherapy. METHODS: In this study, we compared QA testing guidelines from the American College of Radiology (ACR) MR Quality Control (MR QC) Manual to the QA section of the American Association of Physicists in Medicine (AAPM) Task Group 284 report (TG-284). Differences and similarities were identified in testing scope, frequency, and tolerances. QA testing results from an ACR accredited clinical diagnostic MR system following ACR MR QC instructions were then evaluated using TG-284 tolerances. RESULTS: Five tests from the ACR MR QC Manual were not included in TG-284. Five new tests were identified for MR-SIM systems in TG-284 and pertained exclusively to the external laser positioning system of MR-SIM systems. "Low-contrast object detectability" (LCD), "table motion smoothness and accuracy," "transmitter gain," and "geometric accuracy" tests differed between the two QA guides. Tighter tolerances were required in TG-284 for "table motion smoothness and accuracy" and "low contrast object detectability." "Transmitter gain" tolerance was dependent on initial baseline measurements, and TG-284 required that geometric accuracy be tested over a larger field of view than the ACR testing method. All tests from the ACR MR QC Manual for a conventional MR system passed ACR tolerances. The T2-weighted image acquired with ACR sequences failed the 40-spoke requirement from TG-284, transmitter gain was at the 5% tolerance of TG-284, and geometric accuracy could not be evaluated because of required equipment differences. Table motion passed both TG-284 and ACR required tolerances. CONCLUSION: Our study evaluated QA guidelines for an MR-SIM and demonstrated the additional QA requirements of a clinical diagnostic MR system to be used as an MR-SIM in radiotherapy as recommended by TG-284.

Personalized 3D-printed anthropomorphic whole-body phantom irradiated by protons, photons, and neutrons.

The objective of this study was to confirm the feasibility of three-dimensionally-printed (3D-printed), personalized whole-body anthropomorphic phantoms for radiation dose measurements in a variety of charged and uncharged particle radiation fields. We 3D-printed a personalized whole-body phantom of an adult female with a height of 154.8 cm, mass of 90.7 kg, and body mass index of 37.8 kg/m2. The phantom comprised of a hollow plastic shell filled with water and included a watertight access conduit for positioning dosimeters. It is compatible with a wide variety of radiation dosimeters, including ionization chambers that are suitable for uncharged and charged particles. Its mass was 6.8 kg empty and 98 kg when filled with water. Watertightness and mechanical robustness were confirmed after multiple experiments and transportations between institutions. The phantom was irradiated to the cranium with therapeutic beams of 170-MeV protons, 6-MV photons, and fast neutrons. Radiation absorbed dose was measured from the cranium to the pelvis along the longitudinal central axis of the phantom. The dose measurements were made using established dosimetry protocols and well-characterized instruments. For the therapeutic environments considered in this study, stray radiation from intracranial treatment beams was the lowest for proton therapy, intermediate for photon therapy, and highest for neutron therapy. An illustrative example set of measurements at the location of the thyroid for a square field of 5.3 cm per side resulted in 0.09, 0.59, and 1.93 cGy/Gy from proton, photon, and neutron beams, respectively. In this study, we found that 3D-printed personalized phantoms are feasible, inherently reproducible, and well-suited for therapeutic radiation measurements. The measurement methodologies we developed enabled the direct comparison of radiation exposures from neutron, proton, and photon beam irradiations.

Proton Radiotherapy Could Reduce the Risk of Fatal Second Cancers for Children with Intracranial Tumors in Low- and Middle-Income Countries.

PURPOSE: To test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ()(H0: = 1; H A : < 1). RESULTS: Proton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H0 (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old). CONCLUSION: Our findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.

ANALYTICAL MODEL TO ESTIMATE EQUIVALENT DOSE FROM INTERNAL NEUTRONS IN PROTON THERAPY OF CHILDREN WITH INTRACRANIAL TUMORS.

This study developed a computationally efficient and easy-to-implement analytical model to estimate the equivalent dose from secondary neutrons originating in the bodies ('internal neutrons') of children receiving intracranial proton radiotherapy. A two-term double-Gaussian mathematical model was fit to previously published internal neutron equivalent dose per therapeutic absorbed dose versus distance from the field edge calculated using Monte Carlo simulations. The model was trained using three intracranial proton fields of a 9-year-old girl. The resulting model was tested against two intracranial fields of a 10-year-old boy by comparing the mean doses in organs at risk of a radiogenic cancer estimated by the model versus those previously calculated by Monte Carlo. On average, the model reproduced the internal neutron organ doses in the 10-year-old boy within 13.5% of the Monte Carlo at 3-10 cm from the field edge and within a factor of 2 of the Monte Carlo at 10-20 cm from the field edge. Beyond 20 cm, the model poorly estimated H/DRx, however, the values were very small, at <0.03 mSv Gy-1.

Independent application of an analytical model for secondary neutron equivalent dose produced in a passive-scattering proton therapy treatment unit.

The purpose of this study was to independently apply an analytical model for equivalent dose from neutrons produced in a passive-scattering proton therapy treatment unit, H. To accomplish this objective, we applied the previously-published model to treatment plans of two pediatric patients. Their model accounted for neutrons generated by mono-energetic proton beams stopping in a closed aperture. To implement their model to a clinical setting, we adjusted it to account for the area of a collimating aperture, energy modulation, air gap between the treatment unit and patient, and radiation weighting factor. We used the adjusted model to estimate H per prescribed proton absorbed dose, D Rx , for the passive-scattering proton therapy beams of two children, a 9-year-old girl and 10-year-old boy, who each received intracranial boost fields as part of their treatment. In organs and tissues at risk for radiation-induced subsequent malignant neoplasms, T, we calculated the mass-averaged H, H T , per D Rx . Finally, we compared H T /D Rx values to those of previously-published Monte Carlo (MC) simulations of these patients' fields. H T /D Rx values of the adjusted model deviated from the MC result for each organ on average by 20.8 ± 10.0% and 44.2 ± 17.6% for the girl and boy, respectively. The adjusted model underestimated the MC result in all T of each patient, with the exception of the girl's bladder, for which the adjusted model overestimated H T /D Rx by 3.1%. The adjusted model provided a better estimate of H T /D Rx than the unadjusted model. That is, between the two models, the adjusted model reduced the deviation from the MC result by approximately 37.0% and 46.7% for the girl and boy, respectively. We found that the previously-published analytical model, combined with adjustment factors to enhance its clinical applicability, predicted H T /D Rx in out-of-field organs and tissues at risk for subsequent malignant neoplasms with acceptable accuracy. This independent application demonstrated that the analytical model may be useful broadly for clinicians and researchers to calculate equivalent dose from neutrons produced externally to the patient in passive-scattering proton therapy.

Supplemental computational phantoms to estimate out-of-field absorbed dose in photon radiotherapy.

The purpose of this study was to develop a straightforward method of supplementing patient anatomy and estimating out-of-field absorbed dose for a cohort of pediatric radiotherapy patients with limited recorded anatomy. A cohort of nine children, aged 2-14 years, who received 3D conformal radiotherapy for low-grade localized brain tumors (LBTs), were randomly selected for this study. The extent of these patients' computed tomography simulation image sets were cranial only. To approximate their missing anatomy, we supplemented the LBT patients' image sets with computed tomography images of patients in a previous study with larger extents of matched sex, height, and mass and for whom contours of organs at risk for radiogenic cancer had already been delineated. Rigid fusion was performed between the LBT patients' data and that of the supplemental computational phantoms using commercial software and in-house codes. In-field dose was calculated with a clinically commissioned treatment planning system, and out-of-field dose was estimated with a previously developed analytical model that was re-fit with parameters based on new measurements for intracranial radiotherapy. Mean doses greater than 1 Gy were found in the red bone marrow, remainder, thyroid, and skin of the patients in this study. Mean organ doses between 150 mGy and 1 Gy were observed in the breast tissue of the girls and lungs of all patients. Distant organs, i.e. prostate, bladder, uterus, and colon, received mean organ doses less than 150 mGy. The mean organ doses of the younger, smaller LBT patients (0-4 years old) were a factor of 2.4 greater than those of the older, larger patients (8-12 years old). Our findings demonstrated the feasibility of a straightforward method of applying supplemental computational phantoms and dose-calculation models to estimate absorbed dose for a set of children of various ages who received radiotherapy and for whom anatomies were largely missing in their original computed tomography simulations.

Photon caliper to achieve submillimeter positioning accuracy.

The purpose of this study was to demonstrate the feasibility of using a commercial two-dimensional (2D) detector array with an inherent detector spacing of 5 mm to achieve submillimeter accuracy in localizing the radiation isocenter. This was accomplished by delivering the Vernier 'dose' caliper to a 2D detector array where the nominal scale was the 2D detector array and the non-nominal Vernier scale was the radiation dose strips produced by the high-definition (HD) multileaf collimators (MLCs) of the linear accelerator. Because the HD MLC sequence was similar to the picket fence test, we called this procedure the Vernier picket fence (VPF) test. We confirmed the accuracy of the VPF test by offsetting the HD MLC bank by known increments and comparing the known offset with the VPF test result. The VPF test was able to determine the known offset within 0.02 mm. We also cross-validated the accuracy of the VPF test in an evaluation of couch hysteresis. This was done by using both the VPF test and the ExacTrac optical tracking system to evaluate the couch position. We showed that the VPF test was in agreement with the ExacTrac optical tracking system within a root-mean-square value of 0.07 mm for both the lateral and longitudinal directions. In conclusion, we demonstrated the VPF test can determine the offset between a 2D detector array and the radiation isocenter with submillimeter accuracy. Until now, no method to locate the radiation isocenter using a 2D detector array has been able to achieve such accuracy.