AAPM Task Group 334: A guidance document to using radiotherapy immobilization devices and accessories in an MR environment.

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment.

Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy.

BACKGROUND: Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency. METHODS: An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six "experts" (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts. RESULTS: Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM ( P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) ( P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; ( P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM ( P <0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM ( P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM ( P < 0.001). CONCLUSION: FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.

Dosimetric and planning efficiency comparison for lung SBRT: CyberKnife vs VMAT vs knowledge-based VMAT.

This is the first study that compared treatment plan quality and planning efficiency for lung stereotactic body radiation therapy (SBRT) using CyberKnife (CK) Multiplan vs Varian Eclipse treatment planning systems, including volumetric modulated arc therapy (VMAT) and knowledge-based VMAT (KBP-VMAT). Thirteen lung SBRT patients treated with 50 to 55 Gy in 3 or 5 fractions were retrospectively included in this study. CK plans created with Multiplan V. 4.6.1 using 2 fixed circular cones were previously approved used for treatment. For the comparison, the computed tomography (CT) data sets and contours from the CK plans were used to generate VMAT and KBP-VMAT plans (University of California San Diego publicly-shared RapidPlan model) using Eclipse V. 13.7. Metrics used for the comparison of CK, VMAT, and KBP-VMAT plans included monitor units (MUs), conformity indices, dose heterogeneity, high-dose spillage, low-dose spillage, adjacent organs at risk (OAR) doses, and treatment planning time. One-way analysis of variance with post-hoc Tukey tests and paired t-tests were used to analyze the difference of these metrics corresponding to the different planning techniques. All of the 3 planning techniques achieved our clinical goals. With similar planning target volume (PTV) coverage, CK plans yielded the most MU (p< 0.001), the least dose homogeneity (p < 0.002), and the least D2cm dose (p < 0.001), while KBP-VMAT plans resulted in the most OAR sparing. No significant difference was found among other dosimetric metrics such as high-dose spillage, lung V20 and volume receiving 50% of the prescription dose. Compared to VMAT, KBP-VMAT improved OAR sparing (p < 0.05), but required significantly more MU (p < 0.001). KBP-VMAT was associated with the shortest planning time. Eclipse-based VMAT can achieve comparable plan quality for lung SBRT as CK, in a more efficient manner. RapidPlan can facilitate the planning process of KBP-VMAT, with potentially better OAR sparing but higher MU requirements. Further improvement for KBP-VMAT is likely achievable by developing site-specific patient models.

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy-1 to 1 Gy Gy-1) were generally much higher than those for the intracranial irradiations (2.1 µGy Gy-1 to 0.1 Gy Gy-1), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.

A comparison of two pencil beam scanning treatment planning systems for proton therapy.

OBJECTIVE: Analytical dose calculation algorithms for Eclipse and Raystation treatment planning systems (TPS), as well as a Raystation Monte Carlo model are compared to corresponding measured point doses. METHOD: The TPS were modeled with the same beam data acquired during commissioning. Thirty-five typical plans were made with each planning system, 31 without range shifter and four with a 5 cm range shifter. Point doses in these planes were compared to measured doses. RESULTS: The mean percentage difference for all plans between Raystation and Eclipse were 1.51 ± 1.99%. The mean percentage difference for all plans between TPS models and measured values are -2.06 ± 1.48% for Raystation pencil beam (PB), -0.59 ± 1.71% for Eclipse and -1.69 ± 1.11% for Raystation monte carlo (MC). The distribution for the patient plans were similar for Eclipse and Raystation MC with a P-value of 0.59 for a two tailed unpaired t-test and significantly different from the Raystation PB model with P = 0.0013 between Raystation MC and PB. All three models faired markedly better if plans with a 5 cm range shifter were ignored. Plan comparisons with a 5 cm range shifter give differences between Raystation and Eclipse of 3.77 ± 1.82%. The mean percentage difference for 5 cm range shifter plans between TPS models and measured values are -3.89 ± 2.79% for Raystation PB, -0.25 ± 3.85% for Eclipse and 1.55 ± 1.95% for Raystation MC. CONCLUSION: Both Eclipse and Raystation PB TPS are not always accurate within ±3% for a 5 cm range shifters or for small targets. This was improved with the Raystation MC model. The point dose calculations of Eclipse, Raystation PB, and Raystation MC compare within ±3% to measured doses for the other scenarios tested.

Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.

PURPOSE: To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS). METHODS AND MATERIALS: A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage. One time was static and 2 used 4-second, 3-cm peak-to-peak sinusoidal motion with delivery started at maximum inhalation and maximum exhalation. For comparison, all dose measurements were repeated with no repainting and with 8 repaintings. For each motion experiment, the 3%/3-mm gamma pass rate was calculated using the motion-convolved static dose as the reference. Simulations were first validated with the experiments and then used to extend the study to 0- to 5-cm motion magnitude, 2- to 6-second motion periods, patient-measured liver tumor motion, and 1- to 6-fraction treatments. The effect of the proposed method was evaluated for the 5 clinical cases using 4-dimensional (4D) dose reconstruction in the planning 4D computed tomography scan. The target homogeneity index, HI = (D2 - D98)/Dmean, of a single-fraction delivery is reported, where D2 and D98 is the dose delivered to 2% and 98% of the target, respectively, and Dmean is the mean dose. RESULTS: The gamma pass rates were 59.6% ± 9.7% with no repainting, 76.5% ± 10.8% with 8 repaintings, and 92.4% ± 3.8% with the new repainting scheme. Simulations reproduced the experimental gamma pass rates with a 1.3% root-mean-square error and demonstrated largely improved gamma pass rates with the new repainting scheme for all investigated motion scenarios. One- and two-fraction deliveries with the new repainting scheme had gamma pass rates similar to those of 3-4 and 6-fraction deliveries with 8 repaintings. The mean HI for the 5 clinical cases was 14.2% with no repainting, 13.7% with 8 repaintings, 12.0% with the new repainting scheme, and 11.6% for the 4D dose without interplay effects. CONCLUSIONS: A novel repainting strategy for efficient interplay effect mitigation was proposed, implemented, and shown to outperform conventional repainting in experiments, simulations, and dose reconstructions. This strategy could allow for safe and more optimal clinical delivery of thoracic and abdominal proton PBS and better facilitate hypofractionated and stereotactic treatments.

Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data.

PURPOSE: Commissioning beam data for proton spot scanning beams are compared for the first two Varian ProBeam sites in the United States, at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition, the extent to which beams can be matched between gantry rooms at MPTC is investigated. METHOD: Beam data for the two sites were acquired with independent dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites. Spot profiles were acquired at different distances from the isocenter at a gantry angle of 0° as well as a function of gantry angles. Absolute dose calibration was compared between SPTC and the gantries at MPTC. Dosimetric verification of test plans, output as a function of gantry angle, monitor unit (MU) linearity, end effects, dose rate dependence, and plan reproducibility were compared for different gantries at MPTC. RESULTS: The IDDs for the two sites were similar, except in the plateau region, where the SPTC data were on average 4.5% higher for lower energies. This increase in the plateau region decreased as energy increased, with no marked difference for energies higher than 180 MeV. Range in water coincided for all energies within 0.5 mm. The sigmas of the spot profiles in air were within 10% agreement at isocenter. This difference increased as detector distance from the isocenter increased. Absolute doses for the gantries measured at both sites were within 1% agreement. Test plans, output as function of gantry angle, MU linearity, end effects, dose rate dependence, and plan reproducibility were all within tolerances given by TG142. CONCLUSION: Beam data for the two sites and between different gantry rooms were well matched.

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. FROM THE CLINICAL EDITOR: Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities.

A feasibility study using TomoDirect for craniospinal irradiation.

The feasibility of delivering craniospinal irradiation (CSI) with TomoDirect is investigated. A method is proposed to generate TomoDirect plans using standard three-dimensional (3D) beam arrangements on Tomotherapy with junctioning of these fields to minimize hot or cold spots at the cranial/spinal junction. These plans are evaluated and compared to a helical Tomotherapy and a three-dimensional conformal therapy (3D CRT) plan delivered on a conventional linear accelerator (linac) for CSI. The comparison shows that a TomoDirect plan with an overlap between the cranial and spinal fields might be preferable over Tomotherapy plans because of decreased low dose to large volumes of normal tissues outside of the planning target volume (PTV). Although the TomoDirect plans were not dosimetrically superior to a 3D CRT linac plan, the patient can be easily treated in the supine position, which is often more comfortable and efficient from an anesthesia standpoint. TomoDirect plans also have only one setup position which obviates the need for matching of fields and feathering of junctions, two issues encountered with conventional 3D CRT plans. TomoDirect plans can be delivered with comparable treatment times to conventional 3D plans and in shorter times than a Tomotherapy plan. In this paper, a method is proposed for creating TomoDirect craniospinal plans, and the dosimetric consequences for choosing different planning parameters are discussed.

Quantification of artifact reduction with real-time cine four-dimensional computed tomography acquisition methods.

PURPOSE: To quantify the magnitude and frequency of artifacts in simulated four-dimensional computed tomography (4D CT) images using three real-time acquisition methods- direction-dependent displacement acquisition, simultaneous displacement and phase acquisition, and simultaneous displacement and velocity acquisition- and to compare these methods with commonly used retrospective phase sorting. METHODS AND MATERIALS: Image acquisition for the four 4D CT methods was simulated with different displacement and velocity tolerances for spheres with radii of 0.5 cm, 1.5 cm, and 2.5 cm, using 58 patient-measured tumors and respiratory motion traces. The magnitude and frequency of artifacts, CT doses, and acquisition times were computed for each method. RESULTS: The mean artifact magnitude was 50% smaller for the three real-time methods than for retrospective phase sorting. The dose was approximately 50% lower, but the acquisition time was 20% to 100% longer for the real-time methods than for retrospective phase sorting. CONCLUSIONS: Real-time acquisition methods can reduce the frequency and magnitude of artifacts in 4D CT images, as well as the imaging dose, but they increase the image acquisition time. The results suggest that direction-dependent displacement acquisition is the preferred real-time 4D CT acquisition method, because on average, the lowest dose is delivered to the patient and the acquisition time is the shortest for the resulting number and magnitude of artifacts.

Retrospective analysis of artifacts in four-dimensional CT images of 50 abdominal and thoracic radiotherapy patients.

PURPOSE: To quantify the type, frequency, and magnitude of artifacts in four-dimensional (4D) CT images acquired using a multislice cine method. METHODS AND MATERIALS: Fifty consecutive patients who underwent 4D-CT scanning and radiotherapy for thoracic or abdominal cancers were included in this study. All the 4D-CT scans were performed on the GE multislice PET/CT scanner with the Varian Real-time Position Management system in cine mode. The GE Advantage 4D software was used to create 4D-CT data sets. The artifacts were then visually and quantitatively analyzed. We performed statistical analyses to evaluate the relationships between patient- or breathing-pattern-related parameters and the occurrence as well as magnitude of artifacts. RESULTS: It was found that 45 of 50 patients (90%) had at least one artifact (other than blurring) with a mean magnitude of 11.6 mm (range, 4.4-56.0 mm) in the diaphragm or heart. We also observed at least one artifact in 6 of 20 lung or mediastinal tumors (30%). Statistical analysis revealed that there were significant differences between several breathing-pattern-related parameters, including abdominal displacement (p < 0.01), for the subgroups of patients with and without artifacts. The magnitude of an artifact was found to be significantly but weakly correlated with the abdominal displacement difference between two adjacent couch positions (R = 0.34, p < 0.01). CONCLUSIONS: This study has identified that the frequency and magnitude of artifacts in 4D-CT is alarmingly high. Significant improvement is needed in 4D-CT imaging.