High spatiotemporal resolution scintillation imaging of pulsed pencil beam scanning proton beams produced by a gantry-mounted synchrocyclotron.

BACKGROUND: A dosimeter with high spatial and temporal resolution would be of significant interest for pencil beam scanning (PBS) proton beams' characterization, especially when facing small fields and beams with high temporal dynamics. Optical imaging of scintillators has potential in providing sub-millimeter spatial resolution with pulse-by-pulse basis temporal resolution when the imaging system is capable of operating in synchrony with the beam-producing accelerator. PURPOSE: We demonstrate the feasibility of imaging PBS proton beams as they pass through a plastic scintillator detector to simultaneously obtain multiple beam parameters, including proton range, pencil beam's widths at different depths, spot's size, and spot's position on a pulse-by-pulse basis with sub-millimeter resolution. MATERIALS AND METHODS: A PBS synchrocyclotron was used for proton irradiation. A BC-408 plastic scintillator block with 30 × 30 × 5 cm3 size, and another block with 30 × 30 × 0.5 cm3 size, positioned in an optically sealed housing, were used sequentially to measure the proton range, and spot size/location, respectively. A high-speed complementary metal-oxide-semiconductor (CMOS) camera system synchronized with the accelerator's pulses through a gating module was used for imaging. Scintillation images, captured with the camera directly facing the 5-cm-thick scintillator, were corrected for background (BG), and ionization quenching of the scintillator to obtain the proton range. Spots' position and size were obtained from scintillation images of the 0.5-cm-thick scintillator when a 45° mirror was used to reflect the scintillation light toward the camera. RESULTS: Scintillation images with 0.16 mm/pixel resolution corresponding to all proton pulses were captured. Pulse-by-pulse analysis showed that variations of the range, spots' position, and size were within ± 0.2% standard deviation of their average values. The absolute ranges were within ± 1 mm of their expected values. The average spot-positions were mostly within ± 0.8 mm and spots' sigma agreed within 0.2 mm of the expected values. CONCLUSION: Scintillation-imaging PBS beams with high-spatiotemporal resolution is feasible and may help in efficient and cost-effective acceptance testing and commissioning of existing and even emerging technologies such as FLASH, grid, mini-beams, and so forth.

Feasibility of Same-Day Prostate Fiducial Markers, Perirectal Hydrogel Spacer Placement, and Computed Tomography and Magnetic Resonance Imaging Simulation for External Beam Radiation Therapy for Low-Risk and Intermediate-Risk Prostate Cancer.

PURPOSE: The use of prostate fiducial markers and perirectal hydrogel spacers can reduce the acute and late toxic effects associated with prostate radiation therapy. These procedures are usually performed days to weeks before simulation during a separate clinic visit to ensure resolution of procedure-related inflammation. The purpose of this study was to assess whether same-day intraprostatic fiducial marker placement, perirectal hydrogel injection, and computed tomography (CT) and magnetic resonance imaging (MRI) simulation were feasible without adversely affecting hydrogel volume, perirectal spacing, or rectal dose. If feasible, performing these procedures on the same day as simulation would expedite the start of radiation therapy, improve patient convenience, and reduce costs. METHODS AND MATERIALS: Twenty-one patients with clinically localized prostate cancer who were enrolled on a prospective clinical trial (NCT01617161) underwent same-day marker placement, hydrogel injection, and CT and MRI simulation, then underwent T2 MRI verification scans 3 to 4 weeks later. The MRI scans were fused to the CT planning scans by clinical target volumes (CTVs) to generate comparison treatment plans (70 Gy in 28 fractions). Hydrogel volume and symmetry, perirectal spacing, CTV dose, and organ-at-risk dose were evaluated. RESULTS: Verification scans occurred a mean of 24.9 ± 4.6 days after simulation and 9.3 ± 4.9 days after treatment start. Prostate volume did not change between scans (median, 67.3 ± 22.1 cm3 vs 64.1 ± 21.8 cm3; P = .64). The median hydrogel change between simulation and verification was -1.8% ± 4.5% (P = .27). No significant differences in perirectal spacing (midgland: 1.33 ± 0.45 cm vs 1.3 ± 0.7 cm; 1 cm superior: 1.25 ± 0.95 cm vs 1.43 ± 0.91 cm; 1 cm inferior: 1.16 ± 0.28 cm vs 1.41 ± 0.49 cm) were identified. No significant differences in rectal V66 (median 2.3 ± 2.18% vs 2.3 ± 2.28%; P = .99), V35 (median 14.79 ± 7.61 vs 14.67 ± 8.4; P = .73), or D1cc (65.7 ± 9.2 Gy vs 68.2 ± 9.0 Gy; P = .80) were found. All plans met CTV and organ-at-risk constraints. CONCLUSION: Same-day placement of intraprostatic fiducial markers, perirectal hydrogel, and simulation scans was feasible and did not significantly affect hydrogel volume, position, CTV coverage, or rectal dose.

Evaluation of Motion Compensation Methods for Noninvasive Cardiac Radioablation of Ventricular Tachycardia.

PURPOSE: Noninvasive cardiac radioablation is increasingly used for treatment of refractory ventricular tachycardia. Attempts to limit normal tissue exposure are important, including managing motion of the target. An interplay between cardiac and respiratory motion exists for cardiac radioablation, which has not been studied in depth. The objectives of this study were to estimate target motion during abdominal compression free breathing (ACFB) and respiratory gated (RG) deliveries and to investigate the quality of either implanted cardioverter defibrillator lead tip or the diaphragm as a gating surrogate. METHODS AND MATERIALS: Eleven patients underwent computed tomography (CT) simulation with an ACFB 4-dimensional CT (r4DCT) and an exhale breath-hold cardiac 4D-CT (c4DCT). The target, implanted cardioverter defibrillator lead tip and diaphragm trajectories were measured for each patient on the r4DCT and c4DCT using rigid registration of each 4D phase to the reference (0%) phase. Motion ranges for ACFB and exhale (40%-60%) RG delivery were estimated from the target trajectories. Surrogate quality was estimated as the correlation with the target motion magnitudes. RESULTS: Mean (range) target motion across patients from r4DCT was as follows: left/right (LR), 3.9 (1.7-6.9); anteroposterior (AP), 4.1 (2.2-5.4); and superoinferior (SI), 4.7 (2.2-7.9) mm. Mean (range) target motion from c4DCT was as follows: LR, 3.4 (1.0-4.8); AP, 4.3 (2.6-6.5); and SI, 4.1 (1.4-8.0) mm. For an ACFB, treatment required mean (range) margins to be 4.5 (3.1-6.9) LR, 4.8 (3-6.5) AP, and 5.5 (2.3-8.0) mm SI. For RG, mean (range) internal target volume motion would be 3.6 (1.1-4.8) mm LR, 4.3 (2.6-6.5) mm AP, and 4.2 (2.2-8.0) mm SI. The motion correlations between the surrogates and target showed a high level of interpatient variability. CONCLUSIONS: In ACFB patients, a simulated exhale-gated approach did not lead to large projected improvements in margin reduction. Furthermore, the variable correlation between readily available gating surrogates could mitigate any potential advantage to gating and should be evaluated on a patient-specific basis.

Technical Note: Self-shielding evaluation and radiation leakage measurement of a jawless ring gantry linac with a beam stopper.

PURPOSE: To characterize the shielding design and leakage radiation from a newly released ring gantry linac (Halcyon, Varian Medical Systems). METHODS: To assess the radiation leakage surrounding headshield and the radiation level after the beam stopper, measurements were made with GafChromic films. To evaluate the in-room radiation levels, the radiation leakage in the isocenter plane was measured with a large volume spherical ionization chamber (Exradin A6, Standard Imaging). A lead enclosure was constructed to shield the chamber from the low energy scatter radiation from the room. The radiation level at multiple locations was measured with the MLC fully closed and gantry at 0, 45, 90, 135, 180, 225, 270, and 315 degrees. The leakage radiation passing through multiple concrete slabs with various thickness was recorded in a narrow beam geometry to determine the tenth value layer (TVL). RESULTS: A uniform leakage (<0.05%) at 1 m from electron beam line was measured surrounding the linac head with the maximum leakage measured at the top of the head enclosure. The highest radiation level (<0.08%) was measured near the edge of the beam stopper when projected to the measurement plane. The maximum radiation levels due to the head leakage at 15 locations inside the treatment room were recorded and a radiation map was plotted. The maximum leakage was measured at points that along the electron beam line while the gantry at 90 or 270 degree and at the end of head enclosure (0.314%, 0.4 m from electron beamline). The leakage TVL value is found to be 226 mm in a narrow beam geometry with the concrete density of 2.16 g/cm3 or 134.6 lb/cu.ft. CONCLUSION: An overall uniform leakage was measured surrounding linac head. The beam stopper shields the primary radiation with the highest valued measured near the edge of beam stopper. The leakage TVL values are derived and less than the values reported for conventional C-arm linac.

Filmless quality assurance of a Leksell Gamma Knife® Icon™.

PURPOSE: The annual quality assurance (QA) of Leksell Gamma Knife® (LGK) systems are typically performed using films. Film is a good candidate for small field dosimetry due to its high spatial resolution and availability. However, there are multiple challenges with using film; film does not provide real-time measurement and requires batch-specific calibration. Our findings show that active detector-based QA can simplify the procedure and save time without loss of accuracy. METHODS: Annual QA tests for a LGK Icon™ system were performed using both film-based and filmless techniques. Output calibration, relative output factors (ROF), radiation profiles, sector uniformity/source counting, and verification of the unit center point (UCP) and radiation focal point (RFP) coincidence tests were performed. Radiochromic films, two ionization chambers, and a synthetic diamond detector were used for the measurements. Results were compared and verified with the treatment planning system (TPS). RESULTS: The measured dose rate of the LGK Icon was within 0.4% of the TPS value set at the time of commissioning using an ionization chamber. ROF for the 8 and 4-mm collimators were found to be 0.3% and 1.8% different from TPS values using the MicroDiamond detector and 2.6% and 1.9% different for film, respectively. Excellent agreement was found between TPS and measured dose profiles using the MicroDiamond detector which was within 1%/1 mm vs 2%/1 mm for film. Sector uniformity was found to be within 1% for all eight sectors measured using an ionization chamber. Verification of UCP and RFP coincidence using the MicroDiamond detector and pinprick film test was within 0.3 mm at isocenter for both. CONCLUSION: The annual QA of a LGK Icon was successfully performed by employing filmless techniques. Comparable results were obtained using radiochromic films. Utilizing active detectors instead of films simplifies the QA process and saves time without loss of accuracy.

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery.

OBJECTIVE: The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non-small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS: The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS: Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31-86 years). The median follow-up was 7.6 months (range 0.5-81.6 months), and the median survival was 9.3 months (range 1.3-81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS: For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Evaluation of a new secondary dose calculation software for Gamma Knife radiosurgery.

Current available secondary dose calculation software for Gamma Knife radiosurgery falls short in situations where the target is shallow in depth or when the patient is positioned with a gamma angle other than 90°. In this work, we evaluate a new secondary calculation software which utilizes an innovative method to handle nonstandard gamma angles and image thresholding to render the skull for dose calculation. 800 treatment targets previously treated with our GammaKnife Icon system were imported from our treatment planning system (GammaPlan 11.0.3) and a secondary dose calculation was conducted. The agreement between the new calculations and the TPS were recorded and compared to the original secondary dose calculation agreement with the TPS using a Wilcoxon Signed Rank Test. Further comparisons using a Mann-Whitney test were made for targets treated at a 90° gamma angle against those treated with either a 70 or 110 gamma angle for both the new and commercial secondary dose calculation systems. Correlations between dose deviations from the treatment planning system against average target depth were evaluated using a Kendall's Tau correlation test for both programs. The Wilcoxon Signed Rank Test indicated a significant difference in the agreement between the two secondary calculations and the TPS, with a P-value < 0.0001. With respect to patients treated at nonstandard gamma angles, the new software was largely independent of patient setup, while the commercial software showed a significant dependence (P-value < 0.0001). The new secondary dose calculation software showed a moderate correlation with calculation depth, while the commercial software showed a weak correlation (Tau = -.322 and Tau = -.217 respectively). Overall, the new secondary software has better agreement with the TPS than the commercially available secondary calculation software over a range of diverse treatment geometries.

Clinical outcomes and toxicity of proton beam radiation therapy for re-irradiation of locally recurrent breast cancer.

PURPOSE: Repeat radiation therapy (RT) using photons/X-rays for locally recurrent breast cancer results in increased short and long-term toxicity. Proton beam RT (PBRT) can minimize dose to surrounding organs, thereby potentially reducing toxicity. Here, we report the toxicity and clinical outcomes for women who underwent re-irradiation to the chest wall for locally recurrent breast cancer using PBRT. MATERIALS AND METHODS: This was a retrospective study analyzing 16 consecutive patients between 2013 and 2018 with locally recurrent breast cancer who underwent re-irradiation to the chest wall with PBRT. For the recurrent disease, patients underwent maximal safe resection, including salvage mastectomy, wide local excision, or biopsy only per surgeons recommendations. Systemic therapy was used per the recommendation of the medical oncologist. Patients were treated with median dose of 50.4 Cobalt Gray Equivalent (CGyE) in 28 fractions at the time of re-irradiation. Follow-up was calculated from the start of second RT course. Acute toxicities were defined as those occurring during treatment or up to 8 weeks after treatment. Late toxicities were defined as those occurring more than 8 weeks after the completion of therapy. Toxicities were based on CTCAE 4.0. RESULTS: The median age at original diagnosis and at recurrence was 49.8 years and 60.2 years, respectively. The median time between the two RT courses was 10.2 (0.7-20.2) years. The median follow-up time was 18.7 (2.5-35.2) months. No local failures were observed after re-irradiation. One patient developed distant metastasis and ultimately died. Grade 3-4 acute skin toxicity was observed in 5 (31.2%) patients. Four (25%) patients developed chest wall infections during or shortly (2 weeks) after re-irradiation. Late grade 3-4 fibrosis was observed in only 3 (18.8%) patients. Grade 5 toxicities were not observed. Hyperpigmentation was seen in 12 (75%) patients. Pneumonitis, telangiectasia, rib fracture, and lymphedema occurred in 2 (12.5%), 4 (25%), 1 (6.3%), and 1 (6.3%) patients, respectively. CONCLUSIONS: Re-irradiation with PBRT for recurrent breast cancer has acceptable toxicities. There was a high incidence of acute grade 3-4 skin toxicity and infections, which resolved, however, with skin care and antibiotics. Longer follow-up is needed to determine long-term clinical outcomes.

Characterization and validation of an intra-fraction motion management system for masked-based radiosurgery.

PURPOSE: Characterize the intra-fraction motion management (IFMM) system found on the Gamma Knife Icon (GKI), including spatial accuracy, latency, temporal performance, and overall effect on delivered dose. METHODS: A phantom was constructed, consisting of a three-axis translation mount, a remote motorized flipper, and a thermoplastic sphere surrounding a radiation detector. An infrared marker was placed on the translation mount secured to the flipper. The spatial accuracy of the IFMM was measured via the translation mount in all Cartesian planes. The detector was centered at the radiation focal point. A remote signal was used to move the marker out of the IFMM tolerance and pause the beam. A two-channel electrometer was used to record the signals from the detector and the flipper when motion was signaled. These signals determined the latency and temporal performance of the GKI. RESULTS: The spatial accuracy of the IFMM was found to be <0.1 mm. The measured latency was <200 ms. The dose difference with five interruptions was <0.5%. CONCLUSION: This work provides a quantitative characterization of the GKI IFMM system as required by the Nuclear Regulatory Commission. This provides a methodology for GKI users to satisfy these requirements using common laboratory equipment in lieu of a commercial solution.

Radiation Therapy Workflow and Dosimetric Analysis from a Phase 1/2 Trial of Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

PURPOSE: A prospective phase 1/2 trial for electrophysiologic guided noninvasive cardiac radioablation treatment of ventricular tachycardia (ENCORE-VT) demonstrating efficacy for arrhythmia control has recently been reported. The treatment workflow, report dose-volume metrics, and overall process improvements are described here. METHODS AND MATERIALS: Patients receiving 25 Gy in a single fraction to the cardiac ventricular tachycardia substrate (identified on presimulation multimodality imaging) on the phase 1/2 trial were included for analysis. Planning target volume (PTV), R50, monitor unit ratio, and gradient measure values were compared over time using statistical process control. Outlier values in the dose-volume histogram (DVH) for PTV and organs at risk were identified by calculating inner fences based on the interquartile range. Median heart substructure doses are also reported. RESULTS: For the 16 trial patients included, the median target volumes for the gross "target" volumes, internal target volumes, and PTVs were 25.1 cm3 (minimum: 11.5 cm3, maximum: 54.9 cm3), 30.1 cm3 (17.7, 81.6), and 97.9 cm3 (66, 208.5), respectively. On statistical process control analysis, there was a significant decrease in PTV volume among the more recent cohort of cases and mean doses to the nontargeted heart (heart - PTV). Two patients had heart-minus-PTV, esophagus, and stomach DVH data significantly higher than inner fence, and 3 patients had spinal cord DVH data higher than the inner fence, but in all cases the deviations were clinically acceptable. Subjective decreases were seen in the R50, gradient measure, and treatment time from the first to last patient in this series. All plans were verified in phantom with ionization chamber measurements within 2.9% of the expected dose value. CONCLUSIONS: Over the duration of this trial, PTV volumes to the cardiac substrate target decreased significantly, and organ-at-risk constraints were met for all cases. Future directions for this clinical process will include incorporating knowledge-based planning techniques and evaluating the need for substructure optimization.

Validation of post-treatment PET-based dosimetry software for hepatic radioembolization of Yttrium-90 microspheres.

PURPOSE: Yttrium-90 (90 Y) microsphere radioembolization enables selective internal radiotherapy for hepatic malignancies. Currently, there is no standard postdelivery imaging and dosimetry of the microsphere distribution to verify treatment. Recent studies have reported utilizing the small positron yield of 90 Y (32 ppm) with positron emission tomography (PET) to perform treatment verification and dosimetry analysis. In this study, we validated a commercial dosimetry software, MIM SurePlan™ LiverY90 (MIM Software Inc., Cleveland, OH), for clinical use. METHODS: A MATLAB-based algorithm for 90 Y PET-based dosimetry was developed in-house and validated for the purpose of commissioning the commercial software. The algorithm is based on voxel S values and dosimetry formalism reported in MIRD Pamphlet 17. We validated the in-house algorithm to establish it as the ground truth by comparing results from a digital point phantom and a digital uniform cylinder to manual calculations. Once we validated our in-house MATLAB-based algorithm, we used it to perform acceptance testing and commissioning of the commercial dosimetry software, MIM SurePlan, which uses the same dosimetry formalism. A 0.4 cm/5% gamma test was performed on PET-derived dose maps from each algorithm of uniform digital and nonuniform physical phantoms filled with 90 Y chloride solution. Average dose (Davg ) and minimum dose to 70% (D70 ) of a given volume of interest (VOI) were compared for the digital phantom, the physical phantom, and five patient cases (27 tumor VOIs), representing different clinical scenarios. RESULTS: The gamma-pass rates were 97.26% and 97.66% for the digital and physical phantoms, respectively. The differences between Davg and D70 were 0.076% and 0.10% for the digital phantom, respectively, and <5.2% for various VOIs in the physical phantom. In the clinical cases, 96.3% of the VOIs had a difference <5% for Davg , and 88.9% of the VOIs had a difference <5% for D70 . CONCLUSIONS: Dose calculation results from MIM SurePlan were found to be in good agreement with our in-house algorithm. This indicates that MIM SurePlan performs as it should and, hence, can be deemed accepted and commissioned for clinical use for post-implant PET-based dosimetry of 90 Y radioembolization.

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

BACKGROUND: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking. METHODS: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target. The primary safety end point was treatment-related serious adverse events in the first 90 days. The primary efficacy end point was any reduction in VT episodes (tracked by indwelling implantable cardioverter defibrillators) or any reduction in PVC burden (as measured by a 24-hour Holter monitor) comparing the 6 months before and after treatment (with a 6-week blanking window after treatment). Health-related quality of life was assessed using the Short Form-36 questionnaire. RESULTS: Nineteen patients were enrolled (17 for VT, 2 for PVC cardiomyopathy). Median noninvasive ablation time was 15.3 minutes (range, 5.4-32.3). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related serious adverse event. The median number of VT episodes was reduced from 119 (range, 4-292) to 3 (range, 0-31; P<0.001). Reduction was observed for both implantable cardioverter defibrillator shocks and antitachycardia pacing. VT episodes or PVC burden were reduced in 17/18 evaluable patients (94%). The frequency of VT episodes or PVC burden was reduced by 75% in 89% of patients. Overall survival was 89% at 6 months and 72% at 12 months. Use of dual antiarrhythmic medications decreased from 59% to 12% ( P=0.008). Quality of life improved in 5 of 9 Short Form-36 domains at 6 months. CONCLUSIONS: Noninvasive electrophysiology-guided cardiac radioablation is associated with markedly reduced ventricular arrhythmia burden with modest short-term risks, reduction in antiarrhythmic drug use, and improvement in quality of life. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02919618.

First clinical implementation of real-time, real anatomy tracking and radiation beam control.

PURPOSE: We describe the acceptance testing, commissioning, periodic quality assurance, and workflow procedures developed for the first clinically implemented magnetic resonance imaging-guided radiation therapy (MR-IGRT) system for real-time tracking and beam control. METHODS: The system utilizes real-time cine imaging capabilities at 4 frames per second for real-time tracking and beam control. Testing of the system was performed using an in-house developed motion platform and a commercially available motion phantom. Anatomical tracking is performed by first identifying a target (a region of interest that is either tissue to be treated or a critical structure) and generating a contour around it. A boundary contour is also created to identify tracking margins. The tracking algorithm deforms the anatomical contour (target or a normal organ) on every subsequent cine frame and compares it to the static boundary contour. If the anatomy of interest moves outside the boundary, the radiation delivery is halted until the tracked anatomy returns to treatment portal. The following were performed to validate and clinically implement the system: (a) spatial integrity evaluation; (b) tracking accuracy; (c) latency; (d) relative point dose and spatial dosimetry; (e) development of clinical workflow for gating; and (f) independent verification by an outside credentialing service. RESULTS: The spatial integrity of the MR system was found to be within 2 mm over a 45-cm diameter field-of-view. The tracking accuracy for geometric targets was within 1.2 mm. The average system latency was measured to be within 394 ms. The dosimetric accuracy using ionization chambers was within 1.3% ± 1.7%, and the dosimetric spatial accuracy was within 2 mm. The phantom irradiation for the outside credentialing service had satisfactory results, as well. CONCLUSIONS: The first clinical MR-IGRT system was validated for real-time tracking and gating capabilities and shown to be reliable and accurate. Patient workflow methods were developed for efficient treatment. Periodic quality assurance tests can be efficiently performed with commercially available equipment to ensure accurate system performance.

Technical Note: A feasibility study of using the flat panel detector on linac for the kV x-ray generator test.

PURPOSE: To investigate the feasibility of using kV flat panel detector on linac for consistency evaluations of kV x-ray generator performance. METHODS: An in-house designed aluminum (Al) array phantom with six 9 × 9 cm2 square regions having various thickness was proposed and used in this study. Through XML script-driven image acquisition, kV images with various acquisition settings were obtained using the kV flat panel detector. Utilizing pre-established baseline curves, the consistency of x-ray tube output characteristics, including tube voltage accuracy, exposure accuracy and exposure linearity was assessed through image quality assessment metrics including ROI mean intensity, ROI standard deviation (SD), and noise power spectrums (NPS). The robustness of this method was tested on two linacs for a 3-month period. RESULTS: With the proposed method, tube voltage accuracy can be verified through conscience check with a 2% tolerance and 2 kVp intervals for forty different kVp settings. The exposure accuracy can be tested with a 4% consistency tolerance for three mAs settings over forty kVp settings. The exposure linearity tested with 3 mAs settings achieved a coefficient of variation (CV) of 0.1. CONCLUSION: We proposed a novel approach that uses the kV flat panel detector available on linac for x-ray generator test. This approach eliminates the inefficiencies and variability associated with using third-party QA detectors while enabling an automated process.

Normalize the response of EPID in pursuit of linear accelerator dosimetry standardization.

Normalize the response of electronic portal imaging device (EPID) is the first step toward an EPID-based standardization of Linear Accelerator (linac) dosimetry quality assurance. In this study, we described an approach to generate two-dimensional (2D) pixel sensitivity maps (PSM) for EPIDs response normalization utilizing an alternative beam and dark-field (ABDF) image acquisition technique and large overlapping field irradiations. The automated image acquisition was performed by XML-controlled machine operation and the PSM was generated based on a recursive calculation algorithm for Varian linacs equipped with aS1000 and aS1200 imager panels. Cross-comparisons of normalized beam profiles and 1.5%/1.5 mm 1D Gamma analysis was adopted to quantify the improvement of beam profile matching before and after PSM corrections. PSMs were derived for both photon (6, 10, 15 MV) and electron (6, 20 MeV) beams via proposed method. The PSM-corrected images reproduced a horn-shaped profile for photon beams and a relative uniform profiles for electrons. For dosimetrically matched linacs equipped with aS1000 panels, PSM-corrected images showed increased 1D-Gamma passing rates for all energies, with an average 10.5% improvement for crossline and 37% for inline beam profiles. Similar improvements in the phantom study were observed with a maximum improvement of 32% for 15 MV and 22% for 20 MeV. The PSM value showed no significant change for all energies over a 3-month period. In conclusion, the proposed approach correct EPID response for both aS1000 and aS1200 panels. This strategy enables the possibility to standardize linac dosimetry QA and to benchmark linac performance utilizing EPID as the common detector.

Risk assessment of a new acceptance testing procedure for conventional linear accelerators.

PURPOSE: New techniques and materials have recently been developed to expedite the conventional linac acceptance testing procedure (Med Phys. 2017;22), which use the electronic portal imaging device (EPID) for data collection. This new procedure is designed to be more efficient and robust than the conventional approach. The purpose of this work was to perform a comparative risk assessment of the two acceptance testing procedures (ATPs). MATERIALS AND METHODS: Failure Modes and Effects Analysis was used to assess risks for both ATP approaches. Five domain experts (Medical Physicists) comprised the analysis team. The risk assessment method and ranking scales were adopted from the AAPM TG-100. The number of failure pathways and associated risk priority numbers (RPNs) for the two ATP approaches were compared. RPNs > 100 were considered high-priority failure modes. RESULTS: Fewer failure pathways were determined for the new ATP (ATPEPID ) compared to the conventional ATP (ATPconv ) resulting in a 44% difference (n = 233 vs. n = 534, respectively). There were also 35% fewer RPNs > 100 for the ATPEPID (n = 40) compared to the ATPconv (n = 114). Failure pathways and RPNs > 100 for individual ATP tests were 2.0 and 3.5 times higher, on average, for the ATPconv compared to the ATPEPID , respectively. The EPID pixel sensitivity map was identified as a high risk failure for the ATPEPID . CONCLUSIONS: Potential errors due to human factors were decreased for the ATPEPID compared to ATPconv so it is possible that a largely automated linac ATP can mitigate many error occurrences. Manufacturers should be careful when designing an EPID-based ATP to address errors in the EPID pixel sensitivity map which can potentially lead to a significant impact on patients' treatment.

Rapid acceptance testing of modern linac using on-board MV and kV imaging systems.

PURPOSE: The purpose of this study was to develop a novel process for using on-board MV and kV Electronic Portal Imaging Devices (EPIDs) to perform linac acceptance testing (AT) for two reasons: (a) to standardize the assessment of new equipment performance, and (b) to reduce the time to clinical use while reducing physicist workload. METHODS AND MATERIALS: In this study, Varian TrueBeam linacs equipped with amorphous silicon-based EPID (aS1000) were used. The conventional set of AT tests and tolerances were used as a baseline guide. A novel methodology was developed or adopted from published literature to perform as many tests as possible using the MV and kV EPIDs. The developer mode on Varian TrueBeam linacs was used to automate the process. In the EPID-based approach, most of mechanical tests were conducted by acquiring images through a custom phantom and software tools were developed for quantitative analysis to extract different performance parameters. The embedded steel-spheres in a custom phantom provided both visual and radiographic guidance for beam geometry testing. For photon beams, open field EPID images were used to extract inline/crossline profiles to verify the beam energy, flatness and symmetry. EPID images through a double wedge phantom were used for evaluating electron beam properties via diagonal profile. Testing was augmented with a commercial automated application (Machine Performance Check) which was used to perform several geometric accuracy tests such as gantry, collimator rotations, and couch rotations/translations. RESULTS: The developed process demonstrated that the tests, which required customer demonstration, were efficiently performed using EPIDs. The AT tests that were performed using EPIDs were fully automated using the developer mode on the Varian TrueBeam system, while some tests, such as the light field versus radiation field congruence, and collision interlock checks required user interaction. CONCLUSIONS: On-board imagers are quite suitable for both geometric and dosimetric testing of linac system involved in AT. Electronic format of the acquired data lends itself to benchmarking, transparency, as well as longitudinal use of AT data. While the tests were performed on a specific model of a linear accelerator, the proposed approach can be extended to other linacs.

Metal artifact reduction in MRI-based cervical cancer intracavitary brachytherapy.

Magnetic resonance imaging (MRI) plays an increasingly important role in brachytherapy planning for cervical cancer. Yet, metal tandem, ovoid intracavitary applicators, and fiducial markers used in brachytherapy cause magnetic susceptibility artifacts in standard MRI. These artifacts may impact the accuracy of brachytherapy treatment and the evaluation of tumor response by misrepresenting the size and location of the metal implant, and distorting the surrounding anatomy and tissue. Metal artifact reduction sequences (MARS) with high bandwidth RF selective excitations and turbo spin-echo readouts were developed for MRI of orthopedic implants. In this study, metal artifact reduction was applied to brachytherapy of cervical cancer using the orthopedic metal artifact reduction (O-MAR) sequence. O-MAR combined MARS features with view angle tilting and slice encoding for metal artifact correction (SEMAC) to minimize in-plane and through-plane susceptibility artifacts. O-MAR improved visualization of the tandem tip on T2 and proton density weighted (PDW) imaging in phantoms and accurately represented the diameter of the tandem. In a pilot group of cervical cancer patients (N = 7), O-MAR significantly minimized the blooming artifact at the tip of the tandem in PDW MRI. There was no significant difference observed in artifact reduction between the weak (5 kHz, 7 z-phase encodes) and medium (10 kHz, 13 z-phase encodes) SEMAC settings. However, the weak setting allowed a significantly shorter acquisition time than the medium setting. O-MAR also reduced susceptibility artifacts associated with metal fiducial markers so that they appeared on MRI at their true dimensions.

Process improvement for the safe delivery of multidisciplinary-executed treatments-A case in Y-90 microspheres therapy.

PURPOSE: To develop a safe and robust workflow for yttrium-90 (Y-90) radioembolization procedures in a multidisciplinary team environment. METHODS AND MATERIALS: A generalized Define-Measure-Analyze-Improve-Control (DMAIC)-based approach to process improvement was applied to a Y-90 radioembolization workflow. In the first DMAIC cycle, events with the Y-90 workflow were defined and analyzed. To improve the workflow, a web-based interactive electronic white board (EWB) system was adopted as the central communication platform and information processing hub. The EWB-based Y-90 workflow then underwent a second DMAIC cycle. Out of 245 treatments, three misses that went undetected until treatment initiation were recorded over a period of 21 months, and root-cause-analysis was performed to determine causes of each incident and opportunities for improvement. The EWB-based Y-90 process was further improved via new rules to define reliable sources of information as inputs into the planning process, as well as new check points to ensure this information was communicated correctly throughout the process flow. RESULTS: After implementation of the revised EWB-based Y-90 workflow, after two DMAIC-like cycles, there were zero misses out of 153 patient treatments in 1 year. CONCLUSIONS: The DMAIC-based approach adopted here allowed the iterative development of a robust workflow to achieve an adaptable, event-minimizing planning process despite a complex setting which requires the participation of multiple teams for Y-90 microspheres therapy. Implementation of such a workflow using the EWB or similar platform with a DMAIC-based process improvement approach could be expanded to other treatment procedures, especially those requiring multidisciplinary management.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

BACKGROUND: Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). AIM: To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. METHODS: This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. FINDINGS: In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). CONCLUSION: This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI.