Design and implementation of automated notification systems and an electronic whiteboard for radiation therapy planning monitoring.

PURPOSE: Radiotherapy (RT) treatment and treatment planning is a complex process prepared and delivered by a multidisciplinary team of specialists. Efficient communication and notification systems among different team members are therefore essential to ensure the safe, timely delivery of treatments to patients. METHOD: To address this issue, we developed and implemented automated notification systems and an electronic whiteboard to track every CT simulation, contouring task, the new-start schedule, and physician's appointments and tasks, and notify team members of overdue and missing tasks and appointments. The electronic whiteboard was developed to have a straightforward view of current patients' planning workflow and to help different team members coordinate with each other. The systems were implemented and have been used at our center to monitor the progress of treatment-planning tasks for over 2 years. RESULTS: The last-minute plans were relatively reduced by about 40% in 2023 compared to 2021 and 2022 with a p-value < 0.05. The overdue contouring tasks of more than 1 day decreased from 46.8% in 2019 and 33.6% in 2020 to 20%-26.4% in 2021-2023 with a p-value < 0.05 after the implementation of the notification system. The rate of plans with 1-3 day planning time decreased by 20.31%, 39.32%, and 24.08% with a p-value < 0.05 and the rate of plans with 1-3 day planning time due to the contouring task overdue more than 1 day decreased by 49.49%, 56.89%, and 46.52% with a p-value < 0.05 after the implementation. The rate of outstanding appointments that are overdue by more than 7 days decreased by more than 5% with a p-value < 0.05 following the implementation of the system. CONCLUSIONS: Our experience shows that this system requires minimal human intervention, improves the treatment planning workflow and process by reducing errors and delays in the treatment planning process, positively impacts on-time treatment plan completion, and reduces the need for compressed or rushed treatment planning timelines.

A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

Reducing PTV margins for prostate SBRT with motion compensation and gating techniques.

The purpose of this study is to investigate the dosimetric accuracy of prostate SBRT when motion is considered. To account for target movement, motion compensation and gating techniques were investigated with PTV margins reduced to 2 mm. To allow for dosimetric measurements a Delta4 phantom, Gafchromic film, and Hexamotion motion platform were utilized. Four motion files were utilized that represent a range of motions. Analysis of measured prostate motions for fifteen patients was performed to ensure detected motions were similar to those previously reported and motion files utilized were suitable. Five patient plans were utilized to allow for the effects of MLC and target motion interplay to be investigated. For both motion compensation and gating techniques, plans were delivered to the stationary phantom and for each of four motion types with/without compensation/gating enabled. Using a 3%, 2 mm and 80% threshold gamma criteria, film measurements had an average pass rate of 80.5% for uncorrected deliveries versus 96.0% for motion compensated deliveries. For gated techniques average pass rates increased from 89.9% for uncorrected to 94.8% with gating enabled. Measurements with the Delta4 arrays were analyzed with a 3%, 2 mm and 10% threshold dose. An average pass rate of 83.8% was measured for uncorrected motions versus 94.8% with motion compensation. For the gated technique an average pass rate of 87.2% was found for uncorrected motions versus 96.9% with gating enabled. These results show that very high gamma pass rates are achievable when motion compensation or gating techniques are applied. When target motion is not accounted for shifts up to 5 mm in planned versus delivered isodose distributions were found. However, when motion compensation, or gated techniques were applied, much smaller differences between planned and delivered isodose distributions were found. With these techniques dose delivery accuracy is greatly improved, allowing for PTV margins to be reduced.

Volumetric changes of the parotid gland during IMRT based on mid-treatment imaging: implications for parotid stem cell sparing strategies in head and neck cancer.

BACKGROUND: To evaluate the change in parotid glands at mid-treatment during IMRT and the association between radiation dose to the parotid gland stem cell (PGSC) region and patient-reported xerostomia for patients with head and neck cancer (HNC). MATERIAL AND METHODS: Patients who were treated from 2006-2012 at our institution with patient-reported xerostomia outcomes available at least 9 months following RT were included. PG and PGSC regions were delineated and the dose was estimated from the treatment plan dose distribution, using contours from pre- and mid-treatment CT scans. The association between radiation dose and volumetric changes was assessed using linear regression. Univariable logistic regression, logistic dose-response curves, and receiver operating characteristics (ROC) were used to examine the relationship between radiation dose and patient-reported xerostomia. RESULTS: Sixty-three patients were included, most treated with 70 Gy in 33 fractions; 34 patients had mid-treatment CT scans. Both contralateral and ipsilateral PGs had considerable volume reduction from baseline to mid-treatment (25% and 27%, respectively, both p < .001), significantly associated with mean PG dose (-0.44%/Gy, p = .008 and -0.54%/Gy, p < .001, respectively). There was a > 5 Gy difference in mean PG and PGSC dose for 8/34 patients at mid-treatment, with 6/8 (75%) reporting severe xerostomia. Xerostomia prediction based on whole PG or PGSC region dose showed similar performance (ROC AUC 0.754 and 0.749, respectively). The corresponding dose-response models also predicted similar risk of patient-reported xerostomia with mean dose to the contralateral PG (32.5%) or PGSC region (31.4%) at the 20 Gy QUANTEC-recommended sparing level. CONCLUSIONS: The radiation dose to the PGSC region did not show stronger association with patient-reported xerostomia compared to that of whole PG, possibly due to considerable anatomical changes identified at mid-treatment. This shift in the size and position of the PG warrants adaptive planning strategies to evaluate the true benefit of parotid stem cell sparing.

Organ-at-risk dose prediction using a machine learning algorithm: Clinical validation and treatment planning benefit for lung SBRT.

OBJECTIVE: To quantify the clinical performance of a machine learning (ML) algorithm for organ-at-risk (OAR) dose prediction for lung stereotactic body radiation therapy (SBRT) and estimate the treatment planning benefit from having upfront access to these dose predictions. METHODS: ML models were trained using multi-center data consisting of 209 patients previously treated with lung SBRT. Two prescription levels were investigated, 50 Gy in five fractions and 54 Gy in three fractions. Models were generated using a gradient-boosted regression tree algorithm using grid searching with fivefold cross-validation. Twenty patients not included in the training set were used to test OAR dose prediction performance, ten for each prescription. We also performed blinded re-planning based on OAR dose predictions but without access to clinically delivered plans. Differences between predicted and delivered doses were assessed by root-mean square deviation (RMSD), and statistical differences between predicted, delivered, and re-planned doses were evaluated with one-way analysis of variance (ANOVA) tests. RESULTS: ANOVA tests showed no significant differences between predicted, delivered, and replanned OAR doses (all p ≥ 0.36). The RMSD was 2.9, 3.9, 4.3, and 1.7Gy for max dose to the spinal cord, great vessels, heart, and trachea, respectively, for 50 Gy in five fractions. Average improvements of 1.0, 1.4, and 2.0 Gy were seen for spinal cord, esophagus, and trachea max doses in blinded replans compared to clinically delivered plans with 54 Gy in three fractions, and 1.8, 0.7, and 1.5 Gy, respectively, for the esophagus, heart and bronchus max doses with 50 Gy in five fractions. Target coverage was similar with an average PTV V100% of 94.7% for delivered plans compared to 97.3% for blinded re-plans for 50 Gy in five fractions, and respectively 98.4% versus 99.2% for 54 Gy in three fractions. CONCLUSION: This study validated ML-based OAR dose prediction for lung SBRT, showing potential for improved OAR dose sparing and more consistent plan quality using dose predictions for patient-specific planning guidance.

Validation of accuracy deformable image registration contour propagation using a benchmark virtual HN phantom dataset.

Virtual anatomic phantoms offer precise voxel mapping of the variation of anatomy with ground truth deformation vector fields (DVFs). Dice similarity coefficient (DSC) and mean distance to agreement (MDA) are the standard metrics for evaluating geometric contour congruence when testing deformable registration (DIR) algorithms. A HN virtual patient phantom data set was used for a kVCT-kVCT automatic propagation contour validation study employing the Accuray DIR algorithm. Furthermore, since TomoTherapy uses MVCT images of the relevant anatomy for adaptive monitoring, the kVCT image data set quality was transformed to an MVCT image data set quality to study intermodal kVCT-MVCT DIR accuracy. The results of the study indicate that the Accuray DIR algorithm can be expected to autopropagate HN contours adequately, on average, within tolerances recommended by TG-132 (DSC 0.8-0.9, MDA within voxel width). However, contours critical to dosimetric planning should always be visually proofed for accuracy. Using standard reconstruction MVCT image quality causes slightly less, but acceptable, agreement with ground truth contours.

Recommendations of megavoltage computed tomography settings for the implementation of adaptive radiotherapy on helical tomotherapy units.

Megavoltage computed tomography (MVCT) image quality metrics were evaluated on an Accuray Radixact unit to recommend scan settings for the implementation of a consistent adaptive radiotherapy program. Megavoltage computed tomography image quality was evaluated and compared to a kilovoltage CT (kVCT) simulator using a commercial cone beam computed tomography image quality phantom. Megavoltage computed tomographies were acquired on the Accuray Radixact using fine, normal, and coarse pitches, with all available reconstruction slice thicknesses, each of which were reconstructed using standard and iterative reconstruction (IR). Image quality metrics (IQM) were evaluated using DoseLab: automatically and manually calculated spatial resolution, subject contrast, and contrast-to-noise ratio (CNR). Scanning time was 15.6 s/cm for fine, 8.1 s/cm for normal, and 5.6 s/cm for coarse pitch. Automatically evaluated spatial resolutions ranged from 0.39, 0.41, to 0.42 lp/mm for standard reconstruction and from 0.24, 0.21, to 0.18 lp/mm for soft-tissue IR, respectively, with general IR yielding values in between these. Spatial resolution for kVCT was measured to be at least 0.42 lp/mm. Contrast was consistent across MVCT settings with 8.1 ± 0.2%, while kVCT contrast was 10.27 ± 0.05%. CNR was calculated to be 3.3 ± 0.4 for standard reconstruction, 7.4 ± 0.4 for general IR, and 12.0 ± 1.9 for soft-tissue IR. It was found that increasing reconstruction slice thickness for a given pitch does not improve IQMs. Based on the consistency of contrast metrics across pitch values and the only slightly reduced spatial resolution using normal compared to fine pitch, we recommend the use of normal pitch with 2 mm slice thickness to maximize image quality for ART while limiting scanning time. Only for sites for which improved CNR is required and reduced spatial resolution is acceptable, soft-tissue IR is recommended.

A technique to generate synthetic CT from MRI for abdominal radiotherapy.

PURPOSE: To investigate a method to classify tissues types for synthetic CT generation using MRI for treatment planning in abdominal radiotherapy. METHODS: An institutional review board approved volunteer study was performed on a 3T MRI scanner. In-phase, fat and water images were acquired for five volunteers with breath-hold using an mDixon pulse sequence. A method to classify different tissue types for synthetic CT generation in the abdomen was developed. Three tissue clusters (fat, high-density tissue, and spine/air/lungs) were generated using a fuzzy-c means clustering algorithm. The third cluster was further segmented into three sub-clusters that represented spine, air, and lungs. Therefore, five segments were automatically generated. To evaluate segmentation accuracy using the method, the five segments were manually contoured on MRI images as the ground truth, and the volume ratio, Dice coefficient, and Hausdorff distance metric were calculated. The dosimetric effect of segmentation accuracy was evaluated on simulated targets close to air, lungs, and spine using a two-arc volumetric modulated arc therapy (VMAT) technique. RESULTS: The volume ratio of auto-segmentation to manual segmentation was 0.88-2.1 for the air segment and 0.72-1.13 for the remaining segments. The range of the Dice coefficient was 0.24-0.83, 0.84-0.93, 0.94-0.98, 0.93-0.96, and 0.76-0.79 for air, fat, lungs, high-density tissue, and spine, respectively. The range of the mean Hausdorff distance was 3-29.1 mm, 0.5-1.3 mm, 0.4-1 mm, 0.7-1.6 mm, and 1.2-1.4 mm for air, fat, lungs, high-density tissue, and spine, respectively. Despite worse segmentation accuracy in air and spine, the dosimetric effect was 0.2% ± 0.2%, with a maximum difference of 0.8% for all target locations. CONCLUSION: A method to generate synthetic CT in the abdomen was developed, and segmentation accuracy and its dosimetric effect were evaluated. Our results demonstrate the potential of using MRI alone for treatment planning in the abdomen.

Determining efficient helical IMRT modulation factor from the MLC leaf-open time distribution on precision treatment planning system.

PURPOSE: Since the modulation factor (MF) impacts both plan quality and delivery efficiency in tomotherapy Intensity Modulated Radiation Therapy (IMRT) treatment planning, the purpose of this study was to demonstrate a technique in determining an efficient MF from the Multileaf Collimator (MLC) leaf-open time (LOT) distribution of a tomotherapy treatment delivery plan. METHODS: Eight clinical plans of varying complexity were optimized with the highest allowed MF on the Accuracy Precision treatment planning system. Using a central limit theorem argument a range of reduced MFs were then determined from the first two moments of the LOT distribution. A step down approach was used to calculate the reduced-MF plans and plan comparison tools available on the Precision treatment planning system were used to evaluate dose differences with the reference plan. RESULTS: A reduced-MF plan that balanced delivery time and dosimetric quality was found from the set of five MFs determined from the LOT distribution of the reference plan. The reduced-MF plan showed good agreement with the reference plan (target and critical organ dose-volume region of interest dose differences were within 1% and 2% of prescription dose, respectively). DISCUSSION: Plan evaluation and acceptance criteria can vary depending on individual clinical expectations and dosimetric quality trade-offs. With the scheme presented in this paper a planner should be able to efficiently generate a high-quality plan with efficient delivery time without knowing a good MF beforehand. CONCLUSION: A methodology for deriving a reduced MF from the LOT distribution of a high MF treatment plan using the central limit theorem has been presented. A scheme for finding a reduced MF from a set of MFs that results in a plan balanced in both dosimetric quality and treatment delivery efficiency has also been presented.

Two-dimensional solid-state array detectors: A technique for in vivo dose verification in a variable effective area.

PURPOSE: We introduce a technique that employs a 2D detector in transmission mode (TM) to verify dose maps at a depth of dmax in Solid Water. TM measurements, when taken at a different surface-to-detector distance (SDD), allow for the area at dmax (in which the dose map is calculated) to be adjusted. METHODS: We considered the detector prototype "MP512" (an array of 512 diode-sensitive volumes, 2 mm spatial resolution). Measurements in transmission mode were taken at SDDs in the range from 0.3 to 24 cm. Dose mode (DM) measurements were made at dmax in Solid Water. We considered radiation fields in the range from 2 × 2 cm2 to 10 × 10 cm2 , produced by 6 MV flattened photon beams; we derived a relationship between DM and TM measurements as a function of SDD and field size. The relationship was used to calculate, from TM measurements at 4 and 24 cm SDD, dose maps at dmax in fields of 1 × 1 cm2 and 4 × 4 cm2 , and in IMRT fields. Calculations were cross-checked (gamma analysis) with the treatment planning system and with measurements (MP512, films, ionization chamber). RESULTS: In the square fields, calculations agreed with measurements to within ±2.36%. In the IMRT fields, using acceptance criteria of 3%/3 mm, 2%/2 mm, 1%/1 mm, calculations had respective gamma passing rates greater than 96.89%, 90.50%, 62.20% (for a 4 cm SSD); and greater than 97.22%, 93.80%, 59.00% (for a 24 cm SSD). Lower rates (1%/1 mm criterion) can be explained by submillimeter misalignments, dose averaging in calculations, noise artifacts in film dosimetry. CONCLUSIONS: It is possible to perform TM measurements at the SSD which produces the best fit between the area at dmax in which the dose map is calculated and the size of the monitored target.

Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

Immune responses against cancer cells are often hindered by immunosuppressive mechanisms that are developed in the tumor microenvironment. Induction of a hyporesponsive state in tumor Ag-specific T cells is one of the major events responsible for the inability of the adaptive immune system to mount an efficient antitumor response and frequently contributes to lessen the efficacy of immunotherapeutic approaches. Treatment of localized tumors by focused ultrasound (FUS) is a minimally invasive therapy that uses a range of input energy for in situ tumor ablation through the generation of thermal and cavitation effect. Using a murine B16 melanoma tumor model, we show that a variant of FUS that delivers a reduced level of energy at the focal point and generates mild mechanical and thermal stress in target cells has the ability to increase immunogenic presentation of tumor Ags, which results in reversal of tumor-induced T cell tolerance. Furthermore, we show that the combination of nonablative low-energy FUS with an ablative hypofractionated radiation therapy results in synergistic control of primary tumors and leads to a dramatic reduction in spontaneous pulmonary metastases while prolonging recurrence-free survival only in immunocompetent mice.

The evolving role for re-irradiation in the management of recurrent grade 4 glioma.

Although significant gains have been realized in the management of grade 4 glioma, the majority of these patients will ultimately suffer local recurrence within the prior field of treatment. Clearly, novel local treatment strategies are required to improve patient outcomes. Concerns of toxicity have limited enthusiasm for the utilization of re-irradiation as a treatment option. However, using modern imaging technology and precision radiotherapy delivery techniques re-irradiation has proven a feasible option achieving both a palliative benefit and prolongation of survival with low toxicity rates. The evolution of re-irradiation as a treatment modality for recurrent grade 4 glioma is reviewed. In addition, potential targeted radiosensitizers to be used in conjunction with re-irradiation are also discussed.

Single institution experience treating 104 vestibular schwannomas with fractionated stereotactic radiation therapy or stereotactic radiosurgery.

UNLABELLED: The pupose of this study is to assess the long-term outcome and toxicity of fractionated stereotactic radiation therapy (FSRT) and stereotactic radiosurgery (SRS) for 100 vestibular schwannomas treated at a single institution. From 1993 to 2007, 104 patients underwent were treated with radiation therapy for vestibular schwannoma. Forty-eight patients received SRS, with a median prescription dose of 12.5 Gy for SRS (range 9.7-16 Gy). For FSRT, two different fraction schedules were employed: a conventional schedule (ConFSRT) of 1.8 Gy per fraction (Gy/F) for 25 or 28 fractions to a total dose of 45 or 50.4 Gy (n = 19); and a once weekly hypofractionated course (HypoFSRT) consisting of 4 Gy/F for 5 fractions to a total dose of 20 Gy (n = 37). Patients treated with FSRT had better baseline hearing, facial, and trigeminal nerve function, and were more likely to have a diagnosis of NF2. The 5-year progression free rate (PFR) was 97.0 after SRS, 90.5% after HypoFSRT, and 100.0% after ConFSRT (p = NS). Univariate analysis demonstrated that NF2 and larger tumor size (greater than the median) correlated with poorer local control, but prior surgical resection did not. Serviceable hearing was preserved in 60.0% of SRS patients, 63.2% of HypoFSRT patients, and 44.4% of ConFSRT patients (p = 0.6). Similarly, there were no significant differences in 5-year rates of trigeminal toxicity facial nerve toxicity, vestibular dysfunction, or tinnitus. CONCLUSIONS: Equivalent 5-year PFR and toxicity rates are shown for patients with vestibular schwanoma selected for SRS, HypoFSRT, and ConFSRT after multidisciplinary evaluation. Factors correlating with tumor progression included NF2 and larger tumor size.

Radiosensitization beyond DNA damage: Monte Carlo simulations of realistic nanomaterial biodistributions.

We investigated cellular distribution of a tumor-specific gadolinium chelate in 4T1 and U87 cancer cells with the goal to generate more realistic geometries for Monte Carlo simulations of radiation interaction with nanoparticles in cells. Cells were exposed to the agent in-vitro for 30 minutes to 72 hours before being fixed and imaged using transmission electron microscopy. Initially, electron-dense areas consistent with gadolinium were observable throughout the cytoplasm. At six hours those areas were restricted to endosomes and at 24 hours or longer electron dense areas were only found in lysosomes. Lysosomes were on average larger in 4T1 cells, which were exposed to 1 mM concentration compared to U87 cells, exposed to 1 uM. Based on this information we built an extended cell model for Monte Carlo simulations that includes lysosomes with discrete nanoparticle enclaves in addition to mitochondria and the nucleus.

Pulsed reduced-dose rate re-irradiation for patients with recurrent grade 2 gliomas.

Background: Patients with grade 2 glioma exhibit highly variable survival. Re-irradiation for recurrent disease has limited mature clinical data. We report treatment results of pulsed reduced-dose rate (PRDR) radiation for patients with recurrent grade 2 glioma. Methods: A retrospective analysis of 58 patients treated with PRDR from 2000 to 2021 was performed. Radiation was delivered in 0.2 Gy pulses every 3 minutes encompassing tumor plus margin. Survival outcomes and prognostic factors on outcome were Kaplan-Meier and Cox regression analyses. Results: The median survival from the date of initial surgery was 8.6 years (95% CI: 5.5-11.8 years). 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% CI: 8.3-17.0 months) and progression-free survival was 6.2 months (95% CI: 3.8-8.6 months). Overall response rate based on post-PRDR MRI was 36%. In patients who maintained grade 2 histology at recurrence, overall survival from PRDR was 22.0 months with 5 patients remaining disease-free, the longest at 8.2 and 11.4 years. PRDR was generally well tolerated. Conclusions: To the best of our knowledge, this is the largest reported series of patients with recurrent grade 2 gliomas treated with PRDR radiation for disease recurrence. We demonstrate promising survival and acceptable toxicity profiles following re-irradiation. In the cohort of patients who maintain grade 2 disease, prolonged survival (>5 years) is observed in selected patients. For the entire cohort, 1p19q codeletion, KPS, and longer time from initial diagnosis to PRDR were associated with improved survival.

Evaluation of multiple-vendor AI autocontouring solutions.

BACKGROUND: Multiple artificial intelligence (AI)-based autocontouring solutions have become available, each promising high accuracy and time savings compared with manual contouring. Before implementing AI-driven autocontouring into clinical practice, three commercially available CT-based solutions were evaluated. MATERIALS AND METHODS: The following solutions were evaluated in this work: MIM-ProtégéAI+ (MIM), Radformation-AutoContour (RAD), and Siemens-DirectORGANS (SIE). Sixteen organs were identified that could be contoured by all solutions. For each organ, ten patients that had manually generated contours approved by the treating physician (AP) were identified, totaling forty-seven different patients. CT scans in the supine position were acquired using a Siemens-SOMATOMgo 64-slice helical scanner and used to generate autocontours. Physician scoring of contour accuracy was performed by at least three physicians using a five-point Likert scale. Dice similarity coefficient (DSC), Hausdorff distance (HD) and mean distance to agreement (MDA) were calculated comparing AI contours to "ground truth" AP contours. RESULTS: The average physician score ranged from 1.00, indicating that all physicians reviewed the contour as clinically acceptable with no modifications necessary, to 3.70, indicating changes are required and that the time taken to modify the structures would likely take as long or longer than manually generating the contour. When averaged across all sixteen structures, the AP contours had a physician score of 2.02, MIM 2.07, RAD 1.96 and SIE 1.99. DSC ranged from 0.37 to 0.98, with 41/48 (85.4%) contours having an average DSC ≥ 0.7. Average HD ranged from 2.9 to 43.3 mm. Average MDA ranged from 0.6 to 26.1 mm. CONCLUSIONS: The results of our comparison demonstrate that each vendor's AI contouring solution exhibited capabilities similar to those of manual contouring. There were a small number of cases where unusual anatomy led to poor scores with one or more of the solutions. The consistency and comparable performance of all three vendors' solutions suggest that radiation oncology centers can confidently choose any of the evaluated solutions based on individual preferences, resource availability, and compatibility with their existing clinical workflows. Although AI-based contouring may result in high-quality contours for the majority of patients, a minority of patients require manual contouring and more in-depth physician review.

Validation and reproducibility of in vivo dosimetry for pencil beam scanned FLASH proton treatment in mice.

PURPOSE: To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber. METHODS AND MATERIALS: 227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector. RESULTS: Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R2 values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ±â€¯3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ±â€¯0.8 Gy/s and mean local average dose rate of 160.6 ±â€¯3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose. CONCLUSION: In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.

Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves.

Nanoparticle-derived radiosensitization has been investigated by several groups using Monte Carlo simulations and biological modeling. In this work we replicated the physical simulation and biological modeling of previously published research for 50 nm gold nanoparticles irradiated with monoenergetic photons, various 250 kVp photon spectra, and spread-out Bragg peak (SOBP) protons. Monte Carlo simulations were performed using TOPAS and used condensed history Penelope low energy physics models for macroscopic dose deposition and interaction with the nanoparticle; simulation of the microscopic dose deposition from nanoparticle secondaries was performed using Geant4-DNA track structure physics. Biological modeling of survival fractions was performed using a local effect model-type approach for MDA-MB-231 breast cancer cells. Physical simulation results agreed extraordinarily well at all distances (1 nm to 10µm from nanoparticle) for monoenergetic photons and SOBP protons in terms of dose per interaction, dose kernel ratio (often labeled dose enhancement factor), and secondary electron spectra. For 250 kVp photons the influence of the gold K-edge was investigated and found to appreciably affect the results. Calculated survival fractions similarly agreed well within one order of magnitude at macroscopic doses (i.e. without nanoparticle contribution) from 1 Gy to 10 Gy. Several 250 kVp spectra were tested to find one yielding closest agreement with previous results. This highlights the importance of a detailed description of the low energy (< 150 keV) component of photon spectra used forin-silico, as well asin-vitro, andin-vivostudies to ensure reproducibility of the experiments by the scientific community. Both, Monte Carlo simulations of physical interactions of the nanoparticle with photons and protons, as well as the biological modelling of cell survival curves agreed extraordinarily well with previously published data. Further investigation of the stochastic nature of nanoparticle radiosenstiziation is ongoing.

Experience with intraoperative radiation therapy in an urban cancer center.

BACKGROUND/OBJECTIVE: Intra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far. METHODS: We instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age. RESULTS: Between January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months). CONCLUSIONS: IORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic. TRIAL REGISTRATION: All patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).

Case Report: Bilateral targeted intraoperative radiotherapy: a safe and effective alternative for synchronous bilateral breast cancer.

Background: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC. Case reports: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up. Conclusion: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.