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Background: FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation., Purpose: We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments., Methods: Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions., Results: The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm 2 for whole-abdomen and 1.5 × 1.5 cm 2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement., Conclusion: We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications., (© 2024 American Association of Physicists in Medicine.)

Background and Purpose: Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions., Materials and Methods: We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints., Results: FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH., Conclusion: In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom., Methods and Materials: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm 3 ) and polylactic acid (∼1.24 g/cm 3 ) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm 3 ). Hounsfield units (HU), densities, and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom and each institution performed 2 replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film., Results: Compared with the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm 3 for bone, 0.12 g/cm 3 for lung, and 0.03 g/cm 3 for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal effect on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3%-1.2%), and differences from the prescribed dose decreased for both CONV (3.6%-2.5%) and FLASH (6.4%-2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, although these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance., Conclusions: This study marks the first dosimetric audit for FLASH using a nonhomogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biologic findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transcatheter closure of the tubular ducts remains the most challenging procedure, with higher complication rates than other types. This study evaluates the characteristics of transcatheter closure of tubular ducts with pulmonary hypertension. 73 patients with tubular ducts who underwent cardiac catheterization for transcatheter PDA closure were analyzed. The mean age and weight were 1.93 ± 2.68 years and 8.83 ± 6.14 kg, respectively. Transcatheter closure was attempted in 72 patients. Four cases (5.5%) were referred to surgery, while the procedure was completed in the remaining (94.5%). Amplatzer duct occluder (ADO) I or Cardiofix duct occluder (CDO) was the most commonly used devices. However, the use of Amplatzer vascular plug (AVP) II raised in recent years. The most common concern was aortic protrusion/stenosis in ADO I/CDO devices, but most regressed during follow-up. Iatrogenic coarctation of the aorta was observed in two with ADO I/CDO. Embolization of the device to the pulmonary artery was observed in three with CDO, AVP II, and AVP I. Significant left pulmonary artery stenosis requiring stenting developed in one after closure with an MVSDO device. Tubular ducts are highly associated with pulmonary arterial hypertension, and transcatheter closure of them is still challenging despite the developing device armamentarium. Although ADO I or similar devices are widely used, off-label devices are usually needed at increasing rates. The AVP II device is unsuitable for short tubular ducts but seems the best option for long ones., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Biology-guided radiotherapy (BgRT) is a novel technology that uses positron emission tomography (PET) data to direct radiotherapy delivery in real-time. BgRT enables the precise delivery of radiation doses based on the PET signals emanating from PET-avid tumors on the fly. In this way, BgRT uniquely utilizes radiotracer uptake as a biological beacon for controlling and adjusting dose delivery in real-time to account for target motion., Purpose: To demonstrate using real-time PET for BgRT delivery on the RefleXion X1 radiotherapy machine. The X1 radiotherapy machine is a rotating ring-gantry radiotherapy system that generates a nominal 6MV photon beam, PET, and computed tomography (CT) components. The system utilizes emitted photons from PET-avid targets to deliver effective radiation beamlets or pulses to the tumor in real-time., Methods: This study demonstrated a real-time PET BgRT delivery experiment under three scenarios. These scenarios included BgRT delivering to (S 1 ) a static target in a homogeneous and heterogeneous environment, (S 2 ) a static target with a hot avoidance structure and partial PET-avid target, and (S 3 ) a moving target. The first step was to create stereotactic body radiotherapy (SBRT) and BgRT plans (offline PET data supported) using RefleXion's custom-built treatment planning system (TPS). Additionally, to create a BgRT plan using PET-guided delivery, the targets were filled with 18F-Fluorodeoxyglucose (FDG), which represents a tumor/target, that is, PET-avid. The background materials were created in the insert with homogeneous water medium (for S 1 ) and heterogeneous water with styrofoam mesh medium. A heterogeneous background medium simulated soft tissue surrounding the tumor. The treatment plan was then delivered to the experimental setups using a pre-commercial version of the X1 machine. As a final step, the dosimetric accuracy for S 1 and S 2 was assessed using the ArcCheck analysis tool-the gamma criteria of 3%/3 mm. For S 3 , the delivery dose was quantified using EBT-XD radiochromic film. The accuracy criteria were based on coverage, where 100% of the clinical target volume (CTV) receives at least 97% of the prescription dose, and the maximum dose in the CTV was ≤130% of the maximum planned dose (97 % ≤ CTV ≤ 130%)., Results: For the S1, both SBRT and BgRT deliveries had gamma pass rates greater than 95% (SBRT range: 96.9%-100%, BgRT range: 95.2%-98.9%), while in S 2 , the gamma pass rate was 98% for SBRT and between 95.2% and 98.9% for BgRT plan delivering. For S 3 , both SBRT and BgRT motion deliveries met CTV dose coverage requirements, with BgRT plans delivering a very high dose to the target. The CTV dose ranges were (a) SBRT:100.4%-120.4%, and (b) BgRT: 121.3%-139.9%., Conclusions: This phantom-based study demonstrated that PET signals from PET-avid tumors can be utilized to direct real-time dose delivery to the tumor accurately, which is comparable to the dosimetric accuracy of SBRT. Furthermore, BgRT delivered a PET-signal controlled dose to the moving target, equivalent to the dose distribution to the static target. A future study will compare the performance of BgRT with conventional image-guided radiotherapy., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Ultrahigh-dose-rate (FLASH) irradiation has been reported to reduce normal tissue damage compared with conventional dose rate (CONV) irradiation without compromising tumor control. This proof-of-concept study aims to develop a deep learning (DL) approach to quantify the FLASH isoeffective dose (dose of CONV that would be required to produce the same effect as the given physical FLASH dose) with postirradiation mouse intestinal histology images., Methods and Materials: Eighty-four healthy C57BL/6J female mice underwent 16 MeV electron CONV (0.12 Gy/s; n = 41) or FLASH (200 Gy/s; n = 43) single fraction whole abdominal irradiation. Physical dose ranged from 12 to 16 Gy for FLASH and 11 to 15 Gy for CONV in 1 Gy increments. Four days after irradiation, 9 jejunum cross-sections from each mouse were hematoxylin and eosin stained and digitized for histological analysis. CONV data set was randomly split into training (n = 33) and testing (n = 8) data sets. ResNet101-based DL models were retrained using the CONV training data set to estimate the dose based on histological features. The classical manual crypt counting (CC) approach was implemented for model comparison. Cross-section-wise mean squared error was computed to evaluate the dose estimation accuracy of both approaches. The validated DL model was applied to the FLASH data set to map the physical FLASH dose into the isoeffective dose., Results: The DL model achieved a cross-section-wise mean squared error of 0.20 Gy 2 on the CONV testing data set compared with 0.40 Gy 2 of the CC approach. Isoeffective doses estimated by the DL model for FLASH doses of 12, 13, 14, 15, and 16 Gy were 12.19 ± 0.46, 12.54 ± 0.37, 12.69 ± 0.26, 12.84 ± 0.26, and 13.03 ± 0.28 Gy, respectively., Conclusions: Our proposed DL model achieved accurate CONV dose estimation. The DL model results indicate that in the physical dose range of 13 to 16 Gy, the biologic dose response of small intestinal tissue to FLASH irradiation is represented by a lower isoeffective dose compared with the physical dose. Our DL approach can be a tool for studying isoeffective doses of other radiation dose modifying interventions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors., Purpose: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses., Methods: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine 4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis., Results: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine 4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film., Conclusions: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions., (© 2024 American Association of Physicists in Medicine.)

Despite advancements in postoperative outcomes after Fontan surgery, there remains a risk of suboptimal outcomes and significant morbidity in the early postoperative period. Anatomical obstructions in the Fontan pathway can lead to prolonged pleural effusion or ascites, cyanosis, and low cardiac output syndrome (LCOS). Transcatheter interventions offer an alternative to early re-surgery for treating these complications. Over a 13-year period, early catheter angiography, performed within 30 days post-index procedure, was administered to 41 patients, identifying anatomical issues that necessitated re-intervention in 39 cases. This led to transcatheter interventions in 37 (10.4%) of the 344 Fontan surgery patients. The median age was 4.8 years (IQR: 4-9.4), and the median weight was 16.5 kg (IQR: 15-25.2), with females comprising 51.4% (19/37) of this group. The primary indications for the procedures were persistent pleural effusion or ascites in 27 patients (66%), LCOS in 8 patients (20%), and cyanosis in 6 patients (14%). Among the 37 undergoing transcatheter intervention, 30 were treated solely with this method and discharged, three died in ICU follow-up, and four required early re-surgery. No procedural mortality was observed. Our findings demonstrate that transcatheter interventions, including stent implantation, balloon angioplasty, and fenestration dilation, are safe and effective in the early post-Fontan period. Therefore, they should be considered an integral part of the management strategy for this patient group., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan., Methods and Materials: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan., Results: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations., Conclusions: PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In individuals with a single ventricle undergoing evaluation before Fontan surgery, the presence of excessive pulmonary blood flow can contribute to increased pulmonary artery pressure, notably in those who had a Glenn procedure with antegrade pulmonary flow. 28 patients who had previously undergone Glenn anastomosis with antegrade pulmonary blood flow (APBF) and with elevated mean pulmonary artery (mPAP) pressure > 15 mmHg in diagnostic catheter angiography were included in the study. After addressing other anatomical factors that could affect pulmonary artery pressure, APBF was occluded with semi-compliant, Wedge or sizing balloons to measure pulmonary artery pressure accurately. 23 patients (82% of the cohort) advanced to Fontan completion. In this group, median mPAP dropped from 20.5 (IQR 19-22) mmHg to 13 (IQR 12-14) mmHg post-test (p < 0.001). Median PVR post-test was 1.8 (IQR 1.5-2.1) WU m 2 . SpO2 levels decreased from a median of 88% (IQR 86%-93%) pre-test to 80% (IQR 75%-84%) post-test (p < 0.001). In five patients, elevated mPAP post-test occlusion on diagnostic catheter angiography led to non-completion of Fontan circulation. In this group, median pre- and post-test mPAP were 23 mmHg (IQR 21.5-23.5) and 19 mmHg (IQR 18.5-20), respectively (p = 0.038). Median post-test PVR was 3.8 (IQR 3.6-4.5) WU m 2 . SpO2 levels decreased from a median of 79% (IQR 76%-81%) pre-test to 77% (IQR 73.5%-80%) post-test (p = 0.039). Our study presents a specialized approach for patients initially deemed unsuitable for Fontan due to elevated pulmonary artery pressures. We were able to successfully complete the Fontan procedure in the majority of these high-risk cases after temporary balloon occlusion test., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study explores the feasibility of employing Generative Adversarial Networks (GANs) to model the RefleXion X1 Linac. The aim is to investigate the accuracy of dose simulation and assess the potential computational benefits., Methods: The X1 Linac is a new radiotherapy machine with a binary multi-leaf collimation (MLC) system, facilitating innovative biology-guided radiotherapy. A total of 34 GAN generators, each representing a desired MLC aperture, were developed. Each generator was trained using a phase space file generated underneath the corresponding aperture, enabling the generation of particles and serving as a beam source for Monte Carlo simulation. Dose distributions in water were simulated for each aperture using both the GAN and phase space sources. The agreement between dose distributions was evaluated. The computational time reduction from bypassing the collimation simulation and storage space savings were estimated., Results: The percentage depth dose at 10 cm, penumbra, and full-width half maximum of the GAN simulation agree with the phase space simulation, with differences of 0.4 % ± 0.2 %, 0.32 ± 0.66 mm, and 0.26 ± 0.44 mm, respectively. The gamma passing rate (1 %/1mm) for the planar dose exceeded 90 % for all apertures. The estimated time-saving for simulating an plan using 5766 beamlets was 530 CPU hours. The storage usage was reduced by a factor of 102., Conclusion: The utilization of the GAN in simulating the X1 Linac demonstrated remarkable accuracy and efficiency. The reductions in both computational time and storage requirements make this approach highly valuable for future dosimetry studies and beam modeling., Competing Interests: Declaration of competing interest This study was partically supported by a grant from RefleXion Medical Inc., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT., Materials and Methods: We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs) in HEK239T cells, to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated after various irradiation doses, dose rates and oxygen tensions (normoxic, 21% O 2 ; physiological, 4% O 2 ; hypoxic, 2% and 0.5% O 2 ). Electron irradiation was delivered using a FLASH capable Varian Trilogy and the eRT6/Oriatron at CONV (0.08-0.13 Gy/s) and FLASH (1x10 2 -5x10 6 Gy/s) dose rates. Related experiments using clonogenic survival and γH2AX foci in the 293T and the U87 glioblastoma lines were also performed to discern FLASH-RT vs CONV-RT DSB effects., Results: Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Furthermore, RT dose rate modality on U87 cells did not change γH2AX foci numbers at 1- and 24-hours post-irradiation nor did this affect 293T clonogenic survival., Conclusion: Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT., Competing Interests: Declaration of Competing Interest BWL Jr. has received research support outside this work from Varian Medical Systems, is a co-founder and board member of TibaRay, and is a consultant on a clinical trial steering committee for BeiGene. PGM is a co-founder of TibaRay. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Ultrahigh-dose-rate (UHDR) radiation therapy (RT) has produced the FLASH effect in preclinical models: reduced toxicity with comparable tumor control compared with conventional-dose-rate RT. Early clinical trials focused on UHDR RT feasibility using specialized devices. We explore the technical feasibility of practical electron UHDR RT on a standard clinical linear accelerator (LINAC)., Methods and Materials: We tuned the program board of a decommissioned electron energy for UHDR electron delivery on a clinical LINAC without hardware modification. Pulse delivery was controlled using the respiratory gating interface. A short source-to-surface distance (SSD) electron setup with a standard scattering foil was configured and tested on an anthropomorphic phantom using circular blocks with 3- to 20-cm field sizes. Dosimetry was evaluated using radiochromic film and an ion chamber profiler., Results: UHDR open-field mean dose rates at 100, 80, 70, and 59 cm SSD were 36.82, 59.52, 82.01, and 112.83 Gy/s, respectively. At 80 cm SSD, mean dose rate was ∼60 Gy/s for all collimated field sizes, with an R80 depth of 6.1 cm corresponding to an energy of 17.5 MeV. Heterogeneity was <5.0% with asymmetry of 2.2% to 6.2%. The short SSD setup was feasible under realistic treatment conditions simulating broad clinical indications on an anthropomorphic phantom., Conclusions: Short SSD and tuning for high electron beam current on a standard clinical LINAC can deliver flat, homogenous UHDR electrons over a broad, clinically relevant range of field sizes and depths with practical working distances in a configuration easily reversible to standard clinical use., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study explored deep-learning-based patient-specific auto-segmentation using transfer learning on daily RefleXion kilovoltage computed tomography (kVCT) images to facilitate adaptive radiation therapy, based on data from the first group of patients treated with the innovative RefleXion system., Methods and Materials: For head and neck (HaN) and pelvic cancers, a deep convolutional segmentation network was initially trained on a population data set that contained 67 and 56 patient cases, respectively. Then the pretrained population network was adapted to the specific RefleXion patient by fine-tuning the network weights with a transfer learning method. For each of the 6 collected RefleXion HaN cases and 4 pelvic cases, initial planning computed tomography (CT) scans and 5 to 26 sets of daily kVCT images were used for the patient-specific learning and evaluation separately. The performance of the patient-specific network was compared with the population network and the clinical rigid registration method and evaluated by the Dice similarity coefficient (DSC) with manual contours being the reference. The corresponding dosimetric effects resulting from different auto-segmentation and registration methods were also investigated., Results: The proposed patient-specific network achieved mean DSC results of 0.88 for 3 HaN organs at risk (OARs) of interest and 0.90 for 8 pelvic target and OARs, outperforming the population network (0.70 and 0.63) and the registration method (0.72 and 0.72). The DSC of the patient-specific network gradually increased with the increment of longitudinal training cases and approached saturation with more than 6 training cases. Compared with using the registration contour, the target and OAR mean doses and dose-volume histograms obtained using the patient-specific auto-segmentation were closer to the results using the manual contour., Conclusions: Auto-segmentation of RefleXion kVCT images based on the patient-specific transfer learning could achieve higher accuracy, outperforming a common population network and clinical registration-based method. This approach shows promise in improving dose evaluation accuracy in RefleXion adaptive radiation therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to present the first-year experience of treating patients using intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) with a biology-guided radiation therapy machine, the RefleXion X1 system, installed in a clinical setting., Methods and Materials: A total of 78 patients were treated on the X1 system using IMRT and SBRT from May 2021 to May 2022. Clinical and technical data including treatment sites, number of pretreatment kilovoltage computed tomography (kVCT) scans, beam-on time, patient setup time, and imaging time were collected and analyzed. Machine quality assurance (QA) results, machine performance, and user satisfactory survey were also collected and reported., Results: The most commonly treated site was the head and neck (63%), followed by the pelvis (23%), abdomen (8%), and thorax (6%). Except for 5 patients (6%) who received SBRT treatments for bony metastases in the pelvis, all treatments were conventionally fractionated IMRT. The number of kVCT scans per fraction was 1.2 ± 0.5 (mean ± standard deviation). The beam-on time was 9.2 ± 3.5 minutes. The patient setup time and imaging time per kVCT was 4.8 ± 2.6 minutes and 4.6 ± 1.5 minutes, respectively. The daily machine output deviation was 0.4 ± 1.2% from the baseline. The patient QA had a passing rate of 97.4 ± 2.8% at 3%/2 mm gamma criteria. The machine uptime was 92% of the total treatment time. The daily QA and kVCT image quality received the highest level of satisfaction. The treatment workflow for therapists received the lowest level of satisfaction., Conclusions: One year after the installation, 78 patients were successfully treated with the X1 system using IMRT and/or SBRT. With the recent Food and Drug Administration clearance of biology-guided radiation therapy, our department is preparing to treat patients using positron emission tomography-guidance via a new product release, which will address deficiencies in the current image-guided radiation therapy workflow., Competing Interests: Nataliya Kovalchuk reports a relationship with RefleXion Medical that includes funding grants., (© 2023 The Authors.)

Purpose: The aim of this study was to apply the Six Sigma methodology and failure mode and effect analysis (FMEA) to mitigate errors in intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) treatment planning with the first clinical installation of RefleXion X1., Methods and Materials: The Six Sigma approach consisted of 5 phases: define, measure, analyze, improve, and control . The define, measure, and analyze phases consisted of process mapping and an FMEA of IMRT and SBRT treatment planning on the X1. The multidisciplinary team outlined the workflow process and identified and ranked the failure modes associated with the plan check items using the American Association of Physicists in Medicine Task Group 100 recommendations. Items with the highest average risk priority numbers (RPNs) and severity ≥ 7 were prioritized for automation using the Eclipse Scripting Application Programming Interface (ESAPI). The "improve" phase consisted of developing ESAPI scripts before the clinical launch of X1 to improve efficiency and safety. In the "control" phase, the FMEA ranking was re-evaluated 1 year after clinical launch., Results: Overall, 100 plan check items were identified in which the RPN values ranged from 10.2 to 429.0. Fifty of these items (50%) were suitable for automation within ESAPI. Of the 10 highest-risk items, 8 were suitable for automation. Based on the results of the FMEA, 2 scripts were developed: Planning Assistant, used by the planner during preparation for planning, and Automated Plan Check, used by the planner and the plan checker during plan preparation for treatment. After 12 months of clinical use of the X1 and developed scripts, only 3 errors were reported. The average prescript RPN was 138.0, compared with the average postscript RPN of 47.8 ( P < .05), signifying a safer process., Conclusions: Implementing new technology in the clinic can be an error-prone process in which the likelihood of errors increases with increasing pressure to implement the technology quickly. To limit errors in clinical implementation of the novel RefleXion X1 system, the Six Sigma method was used to identify failure modes, establish quality control checks, and re-evaluate these checks 1 year after clinical implementation., (© 2023 The Author(s).)

Objectives: In this study, we characterise the imaging-mode performance of the positron emission tomography (PET) subsystem of the RefleXion X1 machine using the NEMA NU-2 2018 standard., Methods: The X1 machine consists of two symmetrically opposing 90 0 arcs of PET detectors incorporated into the architecture of a ring-gantry linear accelerator rotating up to 60 RPM. PET emissions from a tumour are detected by the PET detectors and used to guide the delivery of radiation beam. Imaging performance of the PET subsystem on X1 machine was evaluated based on sensitivity of the PET detectors, spatial resolution, count-loss performance, image quality, and daily system performance check., Results: PET subsystem sensitivity was measured as 0.183 and 0.161 cps/kBq at the center and off-center positions, respectively. Spatial resolution: average FWHM values of 4.3, 5.1, and 6.7 mm for the point sources at 1, 10, and 20 cm off center, respectively were recorded. For count loss, max NECR: 2.63 kcps, max true coincidence rate: 5.56 kcps, and scatter fraction: 39.8%. The 10 mm sphere was not visible. Image-quality contrast values were: 29.6%, 64.9%, 66.5%, 81.8%, 81.2%, and background variability: 14.8%, 12.4%, 10.3%, 8.8%, 8.3%, for the 13, 17, 22, 28, 37 mm sphere sizes, respectively., Conclusions: When operating in an imaging mode, the spatial resolution and image contrast of the X1 PET subsystem were comparable to those of typical diagnostic imaging systems for large spheres, while the sensitivity and count rate were lower due to the significantly smaller PET detector area in the X1 system. Clinical efficacy when used in BgRT remains to be validated., Advances in Knowledge: This is the first performance evaluation of the PET subsystem on the novel BgRT machine. The dual arcs rotating PET subsystem on RefleXion X1 machine performance is comparable to those of the typical diagnostic PET system based on the spatial resolution and image contrast for larger spheres.

We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12 mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2 mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98-1.03), 1.04 (1.01-1.09), and 1.08 (1.04-1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant ( p > 0.05) based on the Student's t -test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies., Competing Interests: BA received grant support from Varian Medical Systems Inc, Palo Alto CA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kavak, Surucu, Ahn, Pearson and Aydogan.)

Background and Purpose: We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups., Materials and Methods: Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA., Results: Data obtained between replicate experiments for all dosimeters were in excellent agreement (±3%). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose., Conclusion: In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The RefleXion X1 is a novel radiotherapy machine designed for image-guided radiotherapy (IGRT) and biology-guided radiotherapy (BgRT). Its treatment planning system (TPS) generates IMRT and SBRT plans for a 6MV-FFF beam delivered axially via 50 firing positions with the couch advancing every 2.1 mm. The purpose of this work is to report the TPS commissioning results for the first clinical installation of RefleXion™ X1., Methods: CT images of multiple phantoms were imported into the RefleXion TPS to evaluate the accuracy of data transfer, anatomical modeling, plan evaluation, and dose calculation. Comparisons were made between the X1, Eclipse™, and MIM™. Dosimetric parameters for open static fields were evaluated in water and heterogeneous slab phantoms. Representative clinical IMRT and SBRT cases were planned and verified with ion chamber, film, and ArcCHECK @ measurements. The agreement between TPS and measurements for various clinical plans was evaluated using Gamma analysis with a criterion of 3%/2 mm for ArcCHECK @ and film. End-to-end (E2E) testing was performed using anthropomorphic head and lung phantoms., Results: The average difference between the TPS-reported and known HU values was -1.4 ± 6.0 HU. For static fields, the agreements between the TPS-calculated and measured PDD 10 , crossline profiles, and inline profiles (FWHM) were within 1.5%, 1.3%, and 0.5 mm, respectively. Measured output factors agreed with the TPS within 1.3%. Measured and calculated dose for static fields in heterogeneous phantoms agreed within 2.5%. The ArcCHECK @ mean absolute Gamma passing rate was 96.4% ± 3.4% for TG 119 and TG 244 plans and 97.8% ± 3.6% for the 21 clinical plans. E2E film analysis showed 0.8 mm total targeting error for isocentric and 1.1 mm for off-axis treatments., Conclusions: The TPS commissioning results of the RefleXion X1 TPS were within the tolerances specified by AAPM TG 53, MPPG 5.a, TG 119, and TG 148. A subset of the commissioning tests has been identified as baseline data for an ongoing QA program., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

This study reports the beam commissioning results for the first clinical RefleXion Linac., Methods: The X1 produces a 6 MV photon beam and the maximum clinical field size is 40 × 2 cm 2 at source-to-axis distance of 85 cm. Treatment fields are collimated by a binary multileaf collimator (MLC) system with 64 leaves with width of 0.625 cm and y-jaw pairs to provide either a 1 or 2 cm opening. The mechanical alignment of the radiation source, the y-jaw, and MLC were checked with film and ion chambers. The beam parameters were characterized using a diode detector in a compact water tank. In-air lateral profiles and in-water percentage depth dose (PDD) were measured for beam modeling of the treatment planning system (TPS). The lateral profiles, PDDs, and output factors were acquired for field sizes from 1.25 × 1 to 40 × 2 cm 2 field to verify the beam modeling. The rotational output variation and synchronicity were tested to check the gantry angle, couch motion, and gantry rotation., Results: The source misalignments were 0.049 mm in y-direction, 0.66% out-of-focus in x-direction. The divergence of the beam axis was 0.36 mm with a y-jaw twist of 0.03°. Clinical off-axis treatment fields shared a common center in y-direction were within 0.03 mm. The MLC misalignment and twist were 0.57 mm and 0.15°. For all measured fields ranging from the size from 1.25 × 1 to 40 × 2 cm 2 , the mean difference between measured and TPS modeled PDD at 10 cm depth was -0.3%. The mean transverse profile difference in the field core was -0.3% ± 1.1%. The full-width half maximum (FWHM) modeling was within 0.5 mm. The measured output factors agreed with TPS within 0.8%., Conclusions: This study summarizes our specific experience commissioning the first novel RefleXion linac, which may assist future users of this technology when implementing it into their own clinics., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: The first clinical biology-guided radiation therapy (BgRT) system-RefleXion TM X1-was installed and commissioned for clinical use at our institution. This study aimed at evaluating the treatment plan quality and delivery efficiency for IMRT/SBRT cases without PET guidance. Methods: A total of 42 patient plans across 6 cancer sites (conventionally fractionated lung, head, and neck, anus, prostate, brain, and lung SBRT) planned with the Eclipse TM treatment planning system (TPS) and treated with either a TrueBeam ® or Trilogy ® were selected for this retrospective study. For each Eclipse VMAT plan, 2 corresponding plans were generated on the X1 TPS with 10 mm jaws (X1-10mm) and 20 mm jaws (X1-20mm) using our institutional planning constraints. All clinically relevant metrics in this study, including PTV D95%, PTV D2%, Conformity Index (CI), R50, organs-at-risk (OAR) constraints, and beam-on time were analyzed and compared between 126 VMAT and RefleXion plans using paired t -tests. Results: All but 3 planning metrics were either equivalent or superior for the X1-10mm plans as compared to the Eclipse VMAT plans across all planning sites investigated. The Eclipse VMAT and X1-10mm plans generally achieved superior plan quality and sharper dose fall-off superior/inferior to targets as compared to the X1-20mm plans, however, the X1-20mm plans were still considered acceptable for treatment. On average, the required beam-on time increased by a factor of 1.6 across all sites for X1-10mm compared to X1-20mm plans. Conclusions: Clinically acceptable IMRT/SBRT treatment plans were generated with the X1 TPS for both the 10 mm and 20 mm jaw settings.

In this study, we aimed to detect paroxysmal atrial fibrillation episodes before they occur so that patients can take precautions before putting their and others' lives in potentially life-threatening danger. We used the atrial fibrillation prediction database, open data from PhysioNet, and assembled our process based on convolutional neural networks. Conventional heart rate variability features are calculated from time-domain measures, frequency-domain measures using power spectral density estimations, time-frequency-domain measures using wavelet transform, and nonlinear Poincaré plot measures. In addition, we also applied an alternative heart rate normalization, which gave promising results only in a few studies, before calculating these heart rate variability features. We used these features directly and their normalized versions using min-max normalization and z-score normalization methods. Thus, heart rate variability features extracted from six different combinations of these normalizations, in addition to no normalization cases, were applied to the convolutional neural network classifier. We tuned the classifiers' hyperparameters using 90% of feature sets and tested the classifiers' performances using 10% of feature sets. The proposed approach resulted in 87.76% accuracy, 91.30% precision, 80.04% recall, and 87.50% f1-score in heart rate variability with z-score feature normalization. When the heart rate normalization was also utilized, the suggested method gave 100% accuracy, 100% precision, 100% recall, and 100% f1-score in heart rate variability with z-score feature normalization. The proposed method with heart rate normalization and z-score normalization methods resulted in better classification performance than similar studies in the literature. By comparing the existing studies, we conclude that our approach provides a much better tool to determine a near-future paroxysmal atrial fibrillation episode. However, although the achieved benchmarks are impressive, we note that the approach needs to be supported by other studies and on other datasets before clinical trials.

Purpose: The RefleXion™ X1 is a novel radiotherapy system that is designed for image-guided radiotherapy, and eventually, biology-guided radiotherapy (BgRT). BgRT is a treatment paradigm that tracks tumor motion using real-time positron emission signals. This study reports the small-field measurement results and the validation of a Monte Carlo (MC) model of the first clinical RefleXion unit., Methods: The RefleXion linear accelerator (linac) produces a 6 MV flattening filter free (FFF) photon beam and consists of a binary multileaf collimator (MLC) system with 64 leaves and two pairs of y-jaws. The maximum clinical field size achievable is 400 × 20 mm 2 . The y-jaws provide either a 10 or 20 mm opening at source-to-axis distance (SAD) of 850 mm. The width of each MLC leaf at SAD is 6.25 mm. Percentage depth doses (PDDs) and relative beam profiles were acquired using an Edge diode detector in a water tank for field sizes from 12.5 × 10 to 100 × 20 mm 2 . Beam profiles were also measured using films. Output factors of fields ranging from 6.25 × 10 to 100 × 20 mm 2 were measured using W2 scintillator detector, Edge detector, and films. Output correction factors k of the Edge detector for RefleXion were calculated. An MC model of the linac including pre-MLC beam sources and detailed structures of MLC and lower y-jaws was validated against the measurements. Simulation codes BEAMnrc and GATE were utilized., Results: The diode measured PDD at 10 cm depth (PDD10) increases from 53.6% to 56.9% as the field opens from 12.5 × 10 to 100 × 20 mm 2 . The W2-measured output factor increases from 0.706 to 1 as the field opens from 6.25 × 10 to 100 × 20 mm 2 (reference field size). The output factors acquired by diode and film differ from the W2 results by 1.65% (std = 1.49%) and 2.09% (std = 1.41%) on average, respectively. The profile penumbra and full-width half-maximum (FWHM) measured by diode agree well with the film results with a deviation of 0.60 mm and 0.73% on average, respectively. The averaged beam profile consistency calculated between the diode- and film-measured profiles among different depths is within 1.72%. By taking the W2 measurements as the ground truth, the output correction factors k for Edge detector ranging from 0.958 to 1 were reported. For the MC model validation, the simulated PDD10 agreed within 0.6% to the diode measurement. The MC-simulated output factor differed from the W2 results by 2.3% on average (std = 3.7%), while the MC simulated beam penumbra differed from the diode results by 0.67 mm on average (std = 0.42 mm). The MC FWHM agreed with the diode results to within 1.40% on average. The averaged beam profile consistency calculated between the diode and MC profiles among different depths is less than 1.29%., Conclusions: This study represents the first small-field dosimetry of a clinical RefleXion system. A complete and accurate MC model of the RefleXion linac has been validated., (© 2021 American Association of Physicists in Medicine.)

Purpose: The purpose of the study was to determine the incidence of uterine perforations, review the associated complications, and propose guidelines for management of perforations after brachytherapy., Methods and Materials: A retrospective chart review was conducted for all patients with cervical cancer who received single or multiple high-dose-rate brachytherapy implants between April 2006 and May 2017 at a single academic institution. CT and MRI images were retrospectively evaluated to record incidences of uterine perforation of tandem during brachytherapy. Acute and long-term complications during and after treatment were scored using the Common Terminology Criteria for Adverse Events, Version 4.0, of the National Cancer Institute., Results: A total of 123 patients were included in the study. Perforations were observed in 22 patients (17.9%) with 31 (6.4%) of the 482 total implants. Of the different categories of adverse events, only the rate of acute infectious complications among those with perforations (n = 3, 13.6%) versus those without perforations (n = 3, 3.0%) was significant (p = 0.040). Two of the three perforated patients with acute infections had mild urinary tract infections, and all resolved without complications or treatment delays. The remaining one patient had a frank perforation of the anterior uterine wall with a subsequent Grade 3 pyometra infection despite administration of prophylactic antibiotics and 1-week treatment delay. This case was eventually resolved with cervical dilation and evacuation of fluid. Long-term complications were not different between the two arms., Conclusions: Patients with cervical cancer with uterine perforations may be able to safely proceed with brachytherapy treatment without delay or need for prophylactic antibiotics in the acute setting. Further validating data would be able to assist in establishing a new standard of care and help prevent unnecessary and harmful breaks during treatment., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

This paper presents a practical method for converting dose measured with thermoluminescent dosimeters (TLD) to dose in lung and bone for 6 MV and 15 MV photon beams. Monte Carlo (MC) simulations and Burlin cavity theory calculations were performed to calculate [Formula: see text], the dose-to-TLD to dose-to-medium conversion factor. A practical method was proposed for converting TLD-measured-dose to dose-in-medium using the TLD dose calibration in water and [Formula: see text] dose-to-medium to dose-to-water conversion factor. Theoretical calculations for [Formula: see text] were performed using photon spectrum weighted parameters and were compared with MC simulations. Verification of the proposed method was done using phantoms having either bone or lung equivalent slabs stacked in between solid water slabs. Percent depth dose (PDD) curves were measured using 0.089 cm thick LiF:Mg,Ti (TLD-100) dosemeters placed at various depths within these phantoms. They were then corrected with [Formula: see text] factors using the proposed dose conversion method, and were compared with the MC simulations. For 6 MV beam, the MC calculated [Formula: see text] factors were 0.942 and 1.002 for bone and lung, and for 15 MV it was 0.927 and 1.005 for bone and lung, respectively. The difference between the MC simulated and spectrum weighted theoretical [Formula: see text] factors were within 3% for both lung and bone. The PDD curves measured with TLD-100 chips that were corrected using the proposed method agreed well within 1.5% of the MC simulated PDD curves for both the water/lung/water and water/bone/water (WBW) phantoms. The dose-to-medium correction using MC simulated [Formula: see text] is convenient, easy, and accurate. Therefore, it can be used instead of Burlin cavity theory, especially in media with high atomic numbers such as bone for accurate dose quantification.

Purpose: To describe and characterize fast-kV switching, dual-energy (DE) imaging implemented within the on-board imager of a commercial linear accelerator for markerless tumor tracking (MTT)., Methods and Materials: Fast-kV switching, DE imaging provides for rapid switching between programmed tube voltages (ie, 60 and 120 kVp) from one image frame to the next. To characterize this system, the weighting factor used for logarithmic subtraction and signal difference-to-noise ratio were analyzed as a function of time and frame rate. MTT was evaluated using a thorax motion phantom and fast kV, DE imaging was compared versus single energy (SE) imaging over 360 degrees of rotation. A template-based matching algorithm was used to track target motion on both DE and SE sequences. Receiver operating characteristics were used to compare tracking results for both modalities., Results: The weighting factor was inversely related to frame rate and stable over time. After applying the frame rate-dependent weighting factor, the signal difference-to-noise ratio was consistent across all frame rates considered for simulated tumors ranging from 5 to 25 mm in diameter. An analysis of receiver operating characteristics curves showed improved tracking with DE versus SE imaging. The area under the curve for the 10-mm target ranged from 0.821 to 0.858 for SE imaging versus 0.968 to 0.974 for DE imaging. Moreover, the residual tracking errors for the same target size ranged from 2.02 to 2.18 mm versus 0.79 to 1.07 mm for SE and DE imaging, respectively., Conclusions: Fast-kV switching, DE imaging was implemented on the on-board imager of a commercial linear accelerator. DE imaging resulted in improved MTT accuracy over SE imaging. Such an approach may have application for MTT of patients with lung cancer receiving stereotactic body radiation therapy, particularly for small tumors where MTT with SE imaging may fail., (© 2020 The Authors.)

Purpose: Although stereotactic body radiation therapy (SBRT) is an attractive noninvasive approach for liver irradiation, it presents specific challenges associated with respiration-induced liver motion, daily tumor localization due to liver deformation, and poor visualization of target with respect to adjacent normal liver in computed tomography (CT). We aim to identify potential hazards and develop a set of mitigation strategies to improve the safety of our liver SBRT program, using failure mode and effect analysis (FMEA)., Materials and Methods: A multidisciplinary group consisting of two physicians, three physicists, two dosimetrists, and two therapists was formed. A process map covering ten major stages of the liver SBRT program from the initial diagnosis to posttreatment follow-up was generated. A total of 102 failure modes (FM), together with their causes and effects, were identified. The occurrence (O), severity (S), and lack of detectability (D) were independently scored using a scale from 1 (lowest risk) to 10 (largest risk). The ranking was done using the risk probability number (RPN) defined as the product of average O, S, and D numbers for each mode. Two fault tree analyses were performed. The failure modes with the highest RPN values as well as highest severity score were considered for investigation and a set of mitigation strategies was developed to address these., Results: The median RPN (RPN med ) values for all modes ranged from of 9 to 105 and the highest median S score (S med ) was 8. Fourteen FMs were identified to be significant by both RPN med and S med (top ten RPN med ranked and highest S med FMs) and 12 of them were considered for risk mitigation efforts. The remaining two were omitted due to either sufficient checks already in place, or lack of practical mitigation strategies. Implemented measures consisted of five physics tasks, two physician tasks, and three workflow changes., Conclusions: The application of FMEA to our liver SBRT program led to the identification of potential FMs and allowed improvement measures to enhance the safety of our clinical practice., (© 2019 American Association of Physicists in Medicine.)

Objective: Double-chambered right ventricle is characterised by division of the outlet portion of the right ventricle by hypertrophy of the septoparietal trabeculations into two parts. We aim to report our experiences regarding the presenting symptoms of double-chambered right ventricle, long-term prognosis, including the recurrence rate and incidence of arrhythmias after surgery., Methods: We retrospectively investigated 89 consecutive patients who were diagnosed to have double-chambered right ventricle and underwent a surgical intervention from 1995 to 2016. The data obtained by echocardiography, cardiac catheterisation, and surgical findings as well as post-operative follow-up, surgical approaches, post-operative morbidity, mortality, and cardiac events were evaluated., Results: Median age at the time of diagnosis was 2 months and mean age at the time of operation was 5.3 years. Concomitant cardiac anomalies were as follows: perimembranous ventricular septal defect (78 patients), atrial septal defect (9 patients), discrete subaortic membrane (32 patients), right aortic arch (3 patients), aortic valve prolapse and/or mild aortic regurgitation (14 patients), and left superior caval vein (2 patients). The mean follow-up period was 4.86 ± 4.6 years. In these patients, mean systolic pressure gradient in the right ventricle by echocardiography before, immediately, and long-term after surgical intervention was 66.3, 11.8, and 10.4 mmHg, respectively. There were no deaths during the long-term follow-up period. Surgical reinterventions were performed for residual ventricular septal defect (2), residual pulmonary stenosis (1), and severe tricuspid insufficiency (1)., Conclusion: The surgical outcomes and prognosis of double-chambered right ventricle are favourable, recurrence and fatal arrhythmias are unlikely in long-term follow-up.

Purpose: To present a novel method, based on convolutional neural networks (CNN), to automate weighted log subtraction (WLS) for dual-energy (DE) fluoroscopy to be used in conjunction with markerless tumor tracking (MTT)., Methods: A CNN was developed to automate WLS (aWLS) of DE fluoroscopy to enhance soft tissue visibility. Briefly, this algorithm consists of two phases: training a CNN architecture to predict pixel-wise weighting factors followed by application of WLS subtraction to reduce anatomical noise. To train the CNN, a custom phantom was built consisting of aluminum (Al) and acrylic (PMMA) step wedges. Per-pixel ground truth (GT) weighting factors were calculated by minimizing the contrast of Al in the step wedge phantom to train the CNN. The pretrained model was then utilized to predict pixel-wise weighting factors for use in WLS. For comparison, the weighting factor was manually determined in each projection (mWLS). A thorax phantom with five simulated spherical targets (5-25 mm) embedded in a lung cavity, was utilized to assess aWLS performance. The phantom was imaged with fast-kV dual-energy (120 and 60 kVp) fluoroscopy using the on-board imager of a commercial linear accelerator. DE images were processed offline to produce soft tissue images using both WLS methods. MTT was compared using soft tissue images produced with both mWLS and aWLS techniques., Results: Qualitative evaluation demonstrated that both methods achieved soft tissue images with similar quality. The use of aWLS increased the number of tracked frames by 1-5% compared to mWLS, with the largest increase observed for the smallest simulated tumors. The tracking errors for both methods produced agreement to within 0.1 mm., Conclusions: A novel method to perform automated WLS for DE fluoroscopy was developed. Having similar soft tissue quality as well as bone suppression capability as mWLS, this method allows for real-time processing of DE images for MTT., (© 2019 American Association of Physicists in Medicine.)

To evaluate fast-kV switching (FS) dual energy (DE) cone beam computed tomography (CBCT) using the on-board imager (OBI) of a commercial linear accelerator to produce virtual monoenergetic (VM) and relative electron density (RED) images. Using an polynomial attenuation mapping model, CBCT phantom projections obtained at 80 and 140 kVp with FS imaging, were decomposed into equivalent thicknesses of aluminum (Al) and polymethyl methacrylate (PMMA). All projections were obtained with the titanium foil and bowtie filter in place. Basis material projections were then recombined to create VM images by using the linear attenuation coefficients at the specified energy for each material. Similarly, RED images were produced by replacing the linear attenuation values of Al and PMMA by their respective RED values in the projection space. VM and RED images were reconstructed using Feldkamp-Davis-Kress (FDK) and an iterative algorithm (iCBCT, Varian Medical Systems). Hounsfield units (HU), contrast-to-noise ratio (CNR) and RED values were compared against known values. The results after VM-CBCT production showed good material decomposition and consistent HU VM values, with measured root mean square errors (RMSE) from theoretical values, after FDK reconstruction, of 20.5, 5.7, 12.8 and 21.7 HU for 50, 80, 100 and 150 keV, respectively. The largest CNR improvements, when compared to polychromatic images, were observed for the 50 keV VM images. Image noise was reduced up to 28% in the VM-CBCT images after iterative image reconstruction. RED values measured for our method resulted in a mean percentage error of 0.0%  ±  1.8%. This study describes a method to generate VM-CBCT and RED images using FS-DE scans obtained using the OBI of a linac, including the effects of the bowtie filter. The creation of VM and RED images increases the dynamic range of CBCT images, and provides additional data that may be used for adaptive radiotherapy, and on table verification for radiotherapy treatments.

The objective of this study is to determine the energy response factors for BeO optically simulated dosemeter (OSLD) using general cavity theory and Monte Carlo (MC) simulations. A virtual phantom is constructed in EGSnrc MC program and energy response of BeO OSLDs were simulated at 5 cm depth for x-ray beams ranging from 1.25 to 25 MV and at 2 cm for beams with <250 kV including ISO 4037 narrow beam energies in a virtual water phantom. The energy response factor for a given radiation quality relative to 60Co was determined for BeO and compared to the Al2O3:C and LiF:Mg,Ti dosemeters. Burlin cavity theory calculations were done using mean photon energy (MPE) of the beam spectra, while EGSnrc software package was used to carry out MC simulation of full spectra. The cavity theory and MC methods agreed well within the 0.7%. Energy response of x-ray beams at MV range showed a maximum of 1.5% under-response. At energies higher than 150 kV (105 keV MPE) showed no significant difference while a significant under-response were observed at 100 kV (53 keV MPE) and 50 kV (29 keV MPE), ~8 and ~12%, respectively. BeO, Al2O3:C and LiF:Mg,Ti dosemeters exhibited very similar energy response at higher energies mainly in the MeV range. At 50 kV (29 keV MPE), however, BeO dosemeter under responded by a factor of 0.878, while Al2O3:C and LiF:Mg,Ti dosemeters over responded by a factor of 3.2 and 1.44, respectively. Furthermore, at low energies, BeO energy response showed dependence on photon spectra. For instance, at 100 kV, the difference was ~8, ~6 and 2% for 53, 60 and 83 keV MPE (ISO 4037N-100), respectively. Furthermore, calibration with 137Cs instead of 60Co resulted up to 1.8% differences in energy response. Both energy spectrum and calibration methods make considerable differences in energy response of OSLDs. This study concludes that BeO chips are nearly energy independent at energies higher than 100 keV MPE, while Al2O3:C dosemeters show an extremely enhanced energy-response ranging between 1.44 and 3.2 at energies between 170 and 29 keV MPE mainly due to dominance of photoelectric effect., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The aim was to evaluate the role of tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), to identify myocardial dysfunction, and to evaluate myocardial segmental deformation in acute viral myocarditis., Methods: Twenty-one patients and twelve healthy children were studied prospectively. The TDI and STE were performed before and after treatment. The myocardial velocities (S m , E m , and A m ) and time intervals (isovolumic contraction, isovolumic relaxation, and ejection times [ET]) at interventricular septum (IVS), left, and right ventricular basal segments were examined by TDI. The left ventricular global longitudinal strain (LVGLS) and strain rate (LVGLSR), left ventricular global circumferential strain (LVGCS) and strain rate (LVGCSR), and right ventricular global longitudinal strain (RVGLS) and strain rate (RVGLSR) were examined by STE., Results: S m and E m at IVS and at LV, ET at IVS, ET at RV, ET at LV were significantly lower in patients before treatment than controls. LVGLS, LVGLSR, LVGCS, LVGCSR, RVGLS, RVGLSR were significantly decreased in patients before treatment than controls. There was significant improvement for LVGLS, LVGLSR, LVGCS, LVGCSR, and RVGLS in patients after treatment. S m , E m , and A m at LV were significantly lower in patients before treatment than in patients after treatment. In spite of improvements, S m , E m , and ET at IVS, LVGLS, LVGLSR, LVGCS, LVGCSR were significantly lower in patients after treatment than controls., Conclusions: The TDI and STE were useful methods for detection of early myocardial dysfunction and evaluation of treatment outcomes in acute viral myocarditis., (© 2019 Wiley Periodicals, Inc.)

Purpose: To evaluate markerless tumor tracking (MTT) using fast-kV switching dual-energy (DE) fluoroscopy on a bench top system., Methods: Fast-kV switching DE fluoroscopy was implemented on a bench top which includes a turntable stand, flat panel detector, and x-ray tube. The customized generator firmware enables consecutive x-ray pulses that alternate between programmed high and low energies (e.g., 60 and 120 kVp) with a maximum frame rate of 15 Hz. In-house software was implemented to perform weighted DE subtraction of consecutive images to create an image sequence that removes bone and enhances soft tissues. The weighting factor was optimized based on gantry angle. To characterize this system, a phantom was used that simulates the chest anatomy and tumor motion in the lung. Five clinically relevant tumor sizes (5-25 mm diameter) were considered. The targets were programmed to move in the inferior-superior direction of the phantom, perpendicular to the x-ray beam, using a cos 4 waveform to mimic respiratory motion. Target inserts were then tracked with MTT software using a template matching method. The optimal computed tomography (CT) slice thickness for template generation was also evaluated. Tracking success rate and accuracy were calculated in regions of the phantom where the target overlapped ribs vs spine, to compare the performance of single energy (SE) and DE imaging methods., Results: For the 5 mm target, a CT slice thickness of 0.75 mm resulted in the lowest tracking error. For the larger targets (≥10 mm) a CT slice thickness ≤2 mm resulted in comparable tracking errors for SE and DE images. Overall DE imaging improved MTT accuracy, relative to SE imaging, for all tumor targets in a rotational acquisition. Compared to SE, DE imaging increased tracking success rate of small target inserts (5 and 10 mm). For fast motion tracking, success rates improved from 23% to 64% and 74% to 90% for 5 and 10 mm targets inserts overlapping ribs, respectively. For slow moving targets success rates improved from 19% to 59% and 59% to 91% in 5 and 10 mm targets overlapping the ribs, respectively. Similar results were observed when the targets overlapped the spine. For larger targets (≥15 mm) tracking success rates were comparable using SE and DE imaging., Conclusion: This work presents the first results of MTT using fast-kV switching DE fluoroscopy. Using DE imaging has improved the tracking accuracy of MTT, especially for small targets. The results of this study will guide the future implementation of fast-kV switching DE imaging using the on-board imager of a linear accelerator., (© 2019 American Association of Physicists in Medicine.)

Purpose: Our peer-review program previously consisted of weekly chart rounds performed before the end of the first week of treatment. In order to perform peer review before the start of treatment when possible, we implemented daily prospective contouring and planning rounds (CPR)., Methods and Materials: At the time of computed tomography simulation, patients were categorized by the treating physician into 5 treatment groups based on urgency and complexity (ie, standard, urgent, palliative nonemergent, emergent, and special procedures). A scoring system was developed to record the outcome of case presentations, and the results of the CPR case presentations were compared with the time period 2.5 years before CPR implementation, for which peer review was performed retrospectively., Results: CPR was implemented on October 1, 2015, and a total of 4759 patients presented for care through May 31, 2018. The majority were in the standard care path (n = 3154; 66.3%). Among the remainder of the charts, 358 (7.5%), 430 (9.0%), and 179 (3.8%) cases were in the urgent, nonemergent palliative, and emergent care paths, respectively. The remaining patients were in the special procedures group, representing brachytherapy and stereotactic radiosurgery. A total of 125 patients (2.6%) required major changes and were re-presented after the suggested modifications, 102 patients (2.1%) had minor recommendations that did not require a repeat presentation, and 247 cases (5.2%) had minor documentation-related recommendations that did not require editing of the contours. In the 2.5 years before the implementation, records of a total of 1623 patients were reviewed, and only 9 patients (0.6%) had minor recommendation for change. The remainder was noted as complete agreement., Conclusions: Contouring and planning rounds were successfully implemented at our clinic. Pretreatment and, most often, preplanning review of contours and directives allows for a more detailed review and changes to be made early on in the treatment planning process. When compared with historical case presentations, the CPR method made our peer review more thorough and improved standardization.

Dual-energy (DE) imaging using planar imaging with an on-board imager (OBI) is being considered in radiotherapy. We describe here a custom phantom designed to optimize DE imaging parameters using the OBI of a commercial linear accelerator. The phantom was constructed of lung-, tissue- and bone-equivalent material slabs. Five simulated tumors located at two different depths were encased in the lung-equivalent materials. Two slabs with bone-equivalent material inserts were constructed to simulate ribs, which overlap the simulated tumors. DE bone suppression was performed using a weighted logarithmic subtraction based on an iterative method that minimized the contrast between simulated bone- and lung-equivalent materials. The phantom was subsequently used to evaluate different combinations of high-low kV x-ray pairs of images based on the signal-difference-to-noise ratio (SDNR) metric. The results show a strong correlation between tumor visibility and selected energy pairs, where higher energy separation leads to larger SDNR values. To evaluate the effect of image post-processing methods on tumor visibility, an anti-correlated noise reduction (ACNR) technique and adaptive kernel scatter correction method were applied to subsequent DE images. Application of the ACNR technique approximately doubled the SDNR values, hence increasing tumor visibility, while scatter correction had little effect on SDNR values. This phantom allows for quick image acquisition and optimization of imaging parameters and weighting factors. Optimized DE imaging increases soft tissue visibility and may allow for markerless motion tracking of lung tumors.

Purpose: We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency., Methods and Materials: We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography-based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time., Results: The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR ( P = .28). HDR mean V100 and V95 were higher ( P < .0001), but mean V200 and V150 were lower ( P < .0001). HDR rectum V100 and D1cc were lower ( P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001)., Conclusions: We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.

Purpose/objective(s): To evaluate dosimetric differences between MRI-only and MRI-CT planning with a titanium tandem and ovoid applicator to determine if all imaging and planning goals can be achieved with MRI only., Materials/methods: We evaluated 10 patients who underwent MRI-CT-based cervical brachytherapy with a titanium tandem and ovoid applicator. High-risk clinical target volume and organs at risk were contoured on the 3D T2 MRI, which were transferred to the co-registered CT, where the applicator was identified. Retrospectively, three planners independently delineated the applicator on the axial 3D T2 MRI while blinded to the CT. Identical dwell position times in the delivered plan were loaded. Dose-volume histogram parameters were compared to the previously delivered MRI-CT plan., Results: There were no significant differences in dose to D 90 or D 98 of the high-risk clinical target volume with MRI vs. MRI-CT planning. MRI vs. MRI-CT planning resulted in mean D 0.1cc bladder of 8.8 ± 3.4 Gy vs. 8.5 ± 3.2 Gy (p = 0.29) and D 2cc bladder of 6.2 ± 1.4 Gy vs. 6.0 ± 1.4 Gy (p = 0.33), respectively. Mean D 0.1cc rectum was 5.7 ± 1.2 Gy vs. 5.3 ± 1.2 Gy (p = 0.03) and D 2cc rectum 4.0 ± 0.8 Gy vs. 4.2 ± 1.0 Gy (p = 0.18), respectively. Mean D 0.1cc sigmoid was 5.2 ± 1.3 Gy vs. 5.4 ± 1.6 Gy (p = 0.23) and D 2cc sigmoid 3.9 ± 1.0 Gy vs. 4.0 ± 1.1 Gy (p = 0.18), respectively., Conclusion: There were no clinically significant dosimetric differences between the MRI and MRI-CT plans. This study demonstrates that cervical brachytherapy with a titanium applicator can be planned with MRI alone, which is now our clinical standard., (Published by Elsevier Inc.)

Template-based matching algorithms are currently being considered for markerless motion tracking of lung tumors. These algorithms use tumor templates derived from the planning CT scan, and track the motion of the tumor on single energy fluoroscopic images obtained at the time of treatment. In cases where bone may obstruct the view of the tumor, dual energy fluoroscopy may be used to enhance soft tissue contrast. The goal of this study is to predict which tumors will have a high degree of accuracy for markerless motion tracking based on radiomic features obtained from the planning CT scan, using peak-to-sidelobe ratio (PSR) as a surrogate of tracking accuracy. In this study, CT imaging data of 8 lung cancer patients were obtained and analyzed through the open source IBEX program to generate 2,287 radiomic features. Agglomerative hierarchical clustering was used to narrow down these features into 145 clusters comprised of the highest correlation to PSR. The features among the clusters with the least inter-correlation were then chosen to limit redundancy in the data. The results of this study demonstrated a number of radiomic features that are positively correlated to PSR. The features with the highest degree of correlation included complexity, orientation and range. This approach may be used to determine patients for whom markerless motion tracking would be beneficial.

Purpose: Vaginal brachytherapy (VBT) using a cylinder applicator is a standard treatment of intermediate- and high-risk endometrial cancer. We conducted a retrospective study of the dosimetric and clinical outcomes at our institution with 2 single-channel applicators in patients receiving VBT., Methods and Materials: One hundred thirty-six patients with endometrial cancer treated from 2006 to 2016 receiving VBT after definitive surgery were evaluated. Two cylinders were used with the distal dwell position 7.1-12.8 mm from the apex varying by diameter (short channel), and 3.2 mm from the apex (long channel). We prescribed 18-26 Gy in 3-4 fractions at 0.5 cm depth. Measurements of the distance from the apex to the prescription isodose line were taken from CT imaging. Student's t test and the Wilcoxon rank-sum test were used with corrections for multiple comparisons., Results: Patients had International Federation of Gynecology and Obstetrics 2009 Stage I-II disease (70 Stage IA, 58 Stage IB, 9 Stage II). Mean cylinder apex dose was 95.2% and 154.7% of prescription (p < 0.001), and mean distance from apex to the prescription isodose line was 0.54 mm and 3.5 mm (p < 0.001) for the short- and long-channel cylinders, respectively. There were no significant differences in any toxicity between cylinders. Four patients (2.9%) had vaginal recurrence, all of whom were treated with the short-channel cylinder. Cylinder type was not associated with vaginal recurrence (p = 0.27)., Conclusions: A cylinder applicator with a distal dwell position closer to the apex results in higher doses to the vaginal cuff and increased D 2cc to the bladder. All four recurrences were in the short-channel cylinder. Additional investigation into applicator design and impact on patient outcomes in larger cohorts with sufficient followup is warranted., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT)., Methods: We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method., Results: A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1-year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis., Conclusions: Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT.

Brachytherapy (BT), the use of a locally placed or implanted radioactive source for treatment of an adjacent tumor, is an important component in the treatment of patients with both early- and advanced-stage cervical cancer and is increasingly part of the standard treatment protocol. When it is feasible, many radiation oncologists choose to include a magnetic resonance (MR) imaging examination for planning BT treatment (ie, an MR imaging examination after placement of the applicator but before radiation dosing). MR imaging provides excellent soft-tissue contrast and allows radiation oncologists to individualize the radiation dose to the target volume and minimize the dose to adjacent organs that are at risk for radiation damage. However, traditionally, the radiology department has not performed imaging studies for planning, and the requirements are different compared with those of standard diagnostic imaging. In addition, many applicators are available for use in BT treatment of cervical cancer, and each must considered separately to determine MR safety and to define the best imaging parameters. Starting and supporting a robust gynecologic BT program includes implementing imaging protocols that are helpful to both radiation oncologists and diagnostic radiologists. By becoming more familiar with this treatment modality and the logistics of imaging patients undergoing BT, radiologists can provide imaging support for colleagues in the radiation oncology department and better care for patients. © RSNA, 2018.

Aim: To investigate myocardial deformation and function during treatment for Kawasaki disease (KD) in children., Methods: We performed speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI) in 15 children with KD and 15 healthy children during treatment for KD. STE was performed for longitudinal and circumferential strain (S) and strain rate (SR) at the left ventricle (LV) and for longitudinal S and SR at the right ventricle (RV). TDI was performed at the base of interventricular septum (IVS), LV, and RV., Results: Among TDI parameters, E m and ejection time (ET) at IVS, ET at LV and ET at RV obtained obtained before treatment were significantly lower in patients with KD compared to controls. After treatment, in spite of improvements, ET at IVS and ET at RV remained significantly lower in patients with KD compared to controls. Left ventricular global longitudinal and circumferential S and SR values obtained before treatment were significantly lower in patients with KD compared to controls. Left ventricular S and SR values were found to be increased after treatment. However, left ventricular global circumferential S value remained significantly lower in patients with KD compared to controls. There were no significant differences in right ventricular global longitudinal S and SR values between patients and controls before treatment., Conclusion: During acute phase, patients with KD have reduced global left ventricular S and SR which may be more sensitive indicators of myocardial inflammation. This study showed gradual improvements in left ventricular myocardial function during treatment for KD., (© 2017, Wiley Periodicals, Inc.)

Purpose: To demonstrate that optimized pulse sequence parameters for a T2-weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium brachytherapy applicator compared to conventional sequence parameters., Methods and Materials: Following Institutional Review Board approval and informed consent, seven patients were successfully imaged with both standard sagittal T2w fast spin echo parameters (voxel size of 0.98 × 0.78 × 4.0 mm 3 ; readout bandwidth of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w sequence (voxel size of 0.98 × 0.98 × 4.0 mm 3 ; readout bandwidth of 500 Hz/px; repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18-36 slices; and imaging time of 1:15-2:30 min), which had demonstrated artifact reduction in prior phantom work. Visualized intracavitary tandem was hand-segmented by two of the authors. Three body imaging radiologists assessed image quality and intraobserver agreement scores were analyzed., Results: The average segmented volume of the intracavitary applicator significantly (p < 0.05) decreased with the experimental pulse sequence parameters as compared to the standard pulse sequence. Comparison of experimental and standard T2w sequence qualitative scores for each reviewer showed no significant differences between the two techniques., Conclusions: This study demonstrated that pulse sequence parameter optimization can significantly reduce distortion artifact from titanium applicators while maintaining image quality and reasonable imaging times., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: While some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible., Methods and Materials: We identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1-2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost., Results: The median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13-$19,863.03, p < 0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14-$29,511.16, p < 0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p < 0.001)., Conclusions: MRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application., (Published by Elsevier Inc.)

Purpose: To define the relationship between the Point A prescription dose and the dose delivered to various pelvic lymph node groups during high-dose-rate (HDR) brachytherapy treatment of cervical cancer. In less developed countries, brachytherapy is often done without three-dimensional image guidance, instead relying on plain radiography and prescription to Point A. A defined relationship between Point A dose and lymph node doses would help physicians in these health care settings to more accurately estimate nodal doses., Methods and Materials: Treatment data from 50 fractions of HDR brachytherapy of cervical cancer were reviewed, the pelvic lymph nodes were contoured, and dose-volume histogram parameters were obtained. Dose-volume histogram parameters for each contour were normalized as a percentage of the corresponding Point A dose. All nodal groups were divided into left and right sides, except the presacral nodal group., Results and Conclusions: Mean Point A doses were bilateral (Bil) 5.92 Gy ± 0.58, left (L) 5.93 ± 0.59, and right (R) 5.92 ± 0.59. Mean normalized D90 values for the various lymph node groups were as follows-obturator: Bil 20.3% ± 4.5, L 20.5% ± 4.4, and R 20.2% ± 5.2; external iliac: Bil 9.5% ± 2.9, L 10.0% ± 3.1, and R 9.5% ± 3.0; internal iliac: Bil 12.2% ± 3.5, L 12.1% ± 3.4, and R 12.9% ± 4.7; common iliac: Bil 4.3% ± 1.6, L 4.3% ± 1.6, and R 4.3% ± 1.7; and presacral: 8.7% ± 3.4. These relationships can serve as a useful tool for evaluating lymph node doses during HDR brachytherapy of cervical cancer in facilities performing two-dimensional treatment planning and those with limited resources., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program., Methods: We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D 90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D 2cc ) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan-Meier method., Results: Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis-free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D 90 HR-CTV or D 2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D 90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D 2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D 2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09)., Conclusions: There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable., (Published by Elsevier Inc.)