The impact of advancing the standard of care in radiotherapy on operational treatment resources.

PURPOSE: To demonstrate the impact of implementing hypofractionated prescription regimens and advanced treatment techniques on institutional operational hours and radiotherapy personnel resources in a multi-institutional setting. The study may be used to describe the impact of advancing the standard of care with modern radiotherapy techniques on patient and staff resources. METHODS: This study uses radiation therapy data extracted from the radiotherapy information system from two tertiary care, university-affiliated cancer centers from 2012 to 2021. Across all patients in the analysis, the average fraction number for curative and palliative patients was reported each year in the decade. Also, the institutional operational treatment hours are reported for both centers. A sub-analysis for curative intent breast and lung radiotherapy patients was performed to contextualize the impact of changes to imaging, motion management, and treatment technique. RESULTS: From 2012 to 2021, Center 1 had 42 214 patient plans and Center 2 had 43 252 patient plans included in the analysis. Averaged over both centers across the decade, the average fraction number per patient decreased from 6.9 to 5.2 (25%) and 21.8 to 17.2 (21%) for palliative and curative patients, respectively. The operational treatment hours for both institutions increased from 8 h 15 min to 9 h 45 min (18%), despite a patient population increase of 45%. CONCLUSION: The clinical implementation of hypofractionated treatment regimens has successfully reduced the radiotherapy workload and operational treatment hours required to treat patients. This analysis describes the impact of changes to the standard of care on institutional resources.

Skin dose investigations on a 0.5 T parallel rotating biplanar linac-MR using Monte Carlo simulations and measurements.

BACKGROUND: The Alberta rotating biplanar linac-MR has a 0.5 T magnetic field parallel to the beamline. When developing a new linac-MR system, interactions of charged particles with the magnetic field necessitate careful consideration of skin dose and tissue interface effects. PURPOSE: To investigate the effect of the magnetic field on skin dose using measurements and Monte Carlo (MC) simulations. METHODS: We develop an MC model of our linac-MR, which we validate by comparison with ion chamber measurements in a water tank. Additionally, MC simulation results are compared with radiochromic film surface dose measurements on solid water. Variations in surface dose as a function of field size are measured using a parallel plate ion chamber in solid water. Using an anthropomorphic computational phantom with a 2 mm-thick skin layer, we investigate dose distributions resulting from three beam arrangements. Magnetic field on and off scenarios are considered for all measurements and simulations. RESULTS: For a 20 × 20 cm2 field size, D 0.2 c c ${D_{0.2cc}}$ (the minimum dose to the hottest contiguous 0.2 cc volume) for the top 2 mm of a simple water phantom is 72% when the magnetic field is on, compared to 34% with magnetic field off (values are normalized to the central axis dose maximum). Parallel plate ion chamber measurements demonstrate that the relative increase in surface dose due to the magnetic field decreases with increasing field size. For the anthropomorphic phantom, D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ (minimum skin dose in the hottest 1 × 1 × 1 cm3 cube) shows relative increases of 20%-28% when the magnetic field is on compared to when it is off. With magnetic field off, skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ is 71%, 56%, and 21% for medial-lateral tangents, anterior-posterior beams, and a five-field arrangement, respectively. For magnetic field on, the corresponding skin D ∼ 0.2 c c ${D_{ \sim 0.2cc}}$ values are 91%, 67%, and 25%. CONCLUSIONS: Using a validated MC model of our linac-MR, surface doses are calculated in various scenarios. MC-calculated skin dose varies depending on field sizes, obliquity, and the number of beams. In general, the parallel linac-MR arrangement results in skin dose enhancement due to charged particles spiraling along magnetic field lines, which impedes lateral motion away from the central axis. Nonetheless, considering the results presented herein, treatment plans can be designed to minimize skin dose by, for example, avoiding oblique beams and using a larger number of fields.

Monte Carlo modeling of the origin of contaminant electrons on a 0.5T bi-planar Linac-MR.

INTRODUCTION: In the last decade, hybrid linear accelerator magnetic resonance imaging (Linac-MR) devices have evolved into FDA-cleared clinical tools, facilitating magnetic resonance guided radiotherapy (MRgRT). The addition of a magnetic field to radiation therapy has previously demonstrated dosimetric and electron effects regardless of magnetic field orientation. PURPOSE: This study uses Monte Carlo simulations to investigate the importance and efficacy of the magnetic field design in mitigating surface dose enhancement in the Aurora-RT, focusing specifically on contaminant electrons, their origin, and energy spectrum. METHODS: The Aurora-RT 0.5 T Biplanar Linac-MR device was modeled using the BEAMnrc package using the updated EM macros, a magnetic field map generated from Opera 3D. Simulation generated phasespace data at the distal side of the first magnetic pole plate (89 cm) and at machine isocenter (120 cm) were analyzed with respect to electron energy spectra and electron creation origins, both with and without the static magnetic field. RESULTS: The presence of the main magnetic field was verified to affect the origin and distribution of contaminant electrons, removing them from the air column up to 60 cm from the target, and focusing them along the CAX within the region below. Analysis of the remaining electron energy fluence reveals the net removal of electrons with energies > 2 MeV and generation of electrons with energies < 2 MeV in the presence of the static magnetic field as compared to no magnetic field. Moreover, in the presence of the magnetic field the integral energy contained in the contaminant electrons increases from 89 cm to isocenter but is still 15% less overall than the integral energy contained in contaminant electrons without the magnetic field. CONCLUSION: This study provides an analysis of contaminant electrons in the Aurora-RT 0.5 T Linac-MR, emphasizing the role of magnetic field design in successfully minimizing electron contaminants.

Do Dosiomic Features Extracted From Planned 3-Dimensional Dose Distribution Improve Biochemical Failure-Free Survival Prediction: an Analysis Based on a Large Multi-Institutional Data Set.

Purpose: The objective of this work was to investigate whether including additional dosiomic features can improve biochemical failure-free survival prediction compared with models with clinical features only or with clinical features as well as equivalent uniform dose and tumor control probability. Methods and Materials: This retrospective study included 1852 patients who received diagnoses of localized prostate cancer between 2010 and 2016 and were treated with curative external beam radiation therapy in Albert, Canada. A total of 1562 patients from 2 centers were used for developing 3 random survival forest models: Model A included only 5 clinical features; Model B included 5 clinical features, equivalent uniform dose, and tumor control probability; and Model C considered 5 clinical features and 2074 dosiomic features derived from the planned dose distribution of the clinical target volume and planning target volume with further feature selection to determine prognostic features. No feature selection was performed for models A and B. Two hundred ninety patients from another 2 centers were used for independent validation. Individual model-based risk stratification was examined, and the log-rank tests were performed to test statistically significant differences between the risk groups. The 3 models' performances were evaluated using Harrell's concordance index (C-index) and compared using one-way repeated-measures analysis of variance with post hoc paired t test. Results: Model C selected 6 dosiomic features and 4 clinical features to be prognostic. There were statistically significant differences between the 4 risk groups for both training and validation data sets. The C-index for the out-of-bag samples of the training data set was 0.650, 0.648, and 0.669 for models A, B, and C, respectively. The C-index for the validation data set for models A, B, and C was 0.653, 0.648, and 0.662, respectively. Although gains were modest, Model C was statistically significantly better than models A and B. Conclusions: Dosiomics contain information beyond common dose-volume histogram metrics from planned dose distributions. Incorporation of prognostic dosiomic features in biochemical failure-free survival outcome models can lead to statistically significant although modest improvement in performance.

Effect of radiation induced current on the quality of MR images in an integrated linac-MR system.

PURPOSE: In integrated linac-MRI systems, the RF coils are exposed to the linac's pulsed radiation, leading to a measurable radiation induced current (RIC). This work (1) visualizes the RIC in MRI raw data and determines its effect on the MR image signal-to-noise ratio (SNR) (b) examines the effect of linac dose rate on SNR degradations, (c) examines the RIC effect on different MRI sequences, (d) examines the effect of altering the MRI sequence timing on the RIC, and (e) uses a postprocessing method to reduce the RIC signal from the MR raw data. METHODS: MR images were acquired on the linac-MR prototype system using various imaging sequences (gradient echo, spin echo, and bSSFP), dose rates (0, 50, 100, 150, 200, and 250 MU∕min) and repetition times (TR) with the gradient echo sequence. The images were acquired with the radiation beam either directly incident or blocked from the RF coils. The SNR was calculated for each of these scenarios, showing a loss in SNR due to RIC. Finally, a postprocessing method was applied to the image k-space data in order to remove partially the RIC signal and recover some of the lost SNR. RESULTS: The RIC produces visible spikes in the k-space data acquired with the linac's radiation incident on the RF coils. This RIC leads to a loss in imaging SNR that increases with increasing linac dose rate (15%-18% loss at 250 MU∕min). The SNR loss seen with increasing linac dose rate appears to be largely independent of the MR sequence used. Changing the imaging TR had interesting visual effects on the appearance of RIC in k-space due to the timing between the linac's pulsing and the MR sequence, but did not change the SNR loss for a given linac dose rate. The use of a postprocessing algorithm was able to remove much of the RIC noise spikes from the MR image k-space data, resulting in the recovery of a significant portion, up to 81% (Table II), of the lost image SNR. CONCLUSIONS: The presence of RIC in MR RF coils leads to a loss of SNR which is directly related to the linac dose rate. The RIC related loss in SNR is likely to increase for systems that are able to provide larger than 250 MU∕min dose. Some of this SNR loss can be recovered through the use of a postprocessing algorithm, which removes the RIC artefact from the image k-space.

Radiation induced current in the RF coils of integrated linac-MR systems: the effect of buildup and magnetic field.

PURPOSE: In integrated linac-MRI systems, a measurable radiation induced current (RIC) is caused in RF coils by pulsed irradiation. This work (1) tests a buildup method of RIC removal in planar conductors; (2) validates a Monte Carlo method of RIC calculation in metal conductors; and (3) uses the Monte Carlo method to examine the effects of magnetic fields on both planar conductor and practical cylindrical coil geometries. METHODS: The RIC was measured in copper and aluminum plates, taken as the RF coil conductor surrogates, as a function of increasing thickness of buildup materials (teflon and copper). Based on the Penelope Monte Carlo code, a method of RIC calculation was implemented and validated against measurements. This method was then used to calculate the RIC in cylindrical coil geometries with various air gaps between the coil conductor and the enclosed water phantom. Magnetic fields, both parallel and perpendicular to the radiation beam direction, were then included in the simulation program. The effect of magnetic fields on the effectiveness of RIC removal with the application of buildup material was examined in both the planar and the cylindrical geometries. RESULTS: Buildup reduced RIC in metal plate conductors. For copper detector∕copper buildup case, the RIC amplitude was reduced to zero value with 0.15 cm copper buildup. However, when the copper is replaced with teflon as buildup atop the copper conductor, the RIC was only reduced to 80% of its value at zero buildup since the true electronic equilibrium cannot be obtained in this case. For the aluminum detector∕teflon buildup case, the initial amplitude of the RIC was reduced by 90% and 92% in planar aluminum conductor and a surface coil, respectively. In case of cylindrical coils made of aluminum, teflon buildup around the coil's outer surface was generally effective but failed to remove RIC when there was an air gap between the coil and the phantom. Stronger magnetic fields (>0.5 T) perpendicular to the beam direction showed a modest decrease in the RIC for planar conductors with buildup. In the cylindrical geometries, the effect of magnetic fields was very small compared to the effect of introducing air gaps. Loss in signal-to-noise ratio (SNR) due to RIC was reduced from 11% to 5% when a simple buildup was applied to the solenoid in a preliminary experiment. CONCLUSIONS: The RIC in RF coils results from the lack of electronic equilibrium in the coil conductor as the RIC in planar conductor was completely removed by identical buildup of adequate thickness to create electronic equilibrium. The buildup method of RIC removal is effective in cylindrical coil geometry when the coil conductor is in direct contact with the patient. The presence of air makes this method of RIC removal less effective although placing buildup still reduces the RIC by up to 60%. The RIC Monte Carlo simulation is a useful tool for practical coil design where radiation effects must be considered. The SNR is improved in the images obtained concurrently withradiation if buildup is applied to the coil.

A retrospective analysis to demonstrate achievable dosimetry for the left anterior descending artery in left-sided breast cancer patients treated with radiotherapy.

PURPOSE: To demonstrate achievable dose for the left anterior descending artery (LAD) for left-sided breast cancer patients. METHODS: A retrospective analysis was conducted on all left-sided breast cancer patients receiving whole breast or post-mastectomy chest wall irradiation between 2013 and 2018. All patients in this study were treated with tangent-based techniques with the LAD prospectively contoured as routine clinical care. This large patient cohort was used to benchmark achievable mean doses to the LAD in the context of heart dose. The primary cohort of study were patients undergoing treatment with deep-inspiration breath-hold (DIBH), stratified by internal mammary nodes (IMN) inclusion. In all cases, the median (25th-75th percentile) is reported. RESULTS: A total of 1221 left-sided breast cancer patients were included in this study with 1045 in the DIBH cohort. The median heart mean dose for this cohort is 1.0 Gy (0.8-1.1). For patients treated in DIBH with IMNs included (n = 422), the median of the mean LAD dose is 3.6 Gy (2.9-4.4) and, for patients treated in DIBH with IMNs excluded (n = 623), the median of the mean LAD dose is 3.2 Gy (2.5-3.8). CONCLUSIONS: Appropriate respiratory management can be utilized to achieve low dose to the LAD for the majority of patients without compromising target coverage.

Optimization of potent, selective, and orally bioavailable pyrrolodinopyrimidine-containing inhibitors of heat shock protein 90. Identification of development candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide.

A novel class of heat shock protein 90 (Hsp90) inhibitors was discovered by high-throughput screening and was subsequently optimized using a combination of structure-based design, parallel synthesis, and the application of medicinal chemistry principles. Through this process, the biochemical and cell-based potency of the original HTS lead were substantially improved along with the corresponding metabolic stability properties. These efforts culminated with the identification of a development candidate (compound 42) which displayed desired PK/PD relationships, significant efficacy in a melanoma A2058 xenograft tumor model, and attractive DMPK profiles.

Phantom materials for single point imaging pulse sequences.

The popularity of pure phase encode MRI techniques, including single point imaging (SPI), is steadily increasing, particularly in instances where the samples of interest are solid-like, or for other reasons possess short effective transverse relaxation times, T2*. As the interest in these techniques grows, so too does the need for a phantom material which is representative of this class of samples. The characteristics of such a phantom should include chemical and physical stability, straightforward preparation, high signal to noise ratio and relaxation times which are both easily manipulated and representative. To this end, we have developed a gelatin/sucrose-based gel which addresses the above criteria and behaves as a very flexible short T2* phantom. An order of magnitude variation in T1 and T2 can be achieved over a reasonable range of sucrose concentration. Even larger changes can be achieved with the addition of further doping agents.