CT Simulation Research Articles

Heatmaps to Assess Tumor Motion Probability with MRcine in Head and Neck Cancer

Intrafraction motion affects tumor position during radiation for head and neck cancers (HNC) and can be assessed using magnetic resonance cine (MR-cine). Heatmaps - visual representation of patient specific temporal tumor location akin to internal target volume (ITV) - were analyzed to demonstrate the variation of population-based motion margins in primary oropharyngeal (OP) and laryngeal/hypopharyngeal (LH) sites with the goal to provide insights towards personalized margins. MR-cine were performed for LH and OP HNC patients as part of simulation protocol. Images (900-1500 slices) were acquired across 3-5 minutes per patient. Gross target volumes were propagated on T1 contrast sagittal sequence using deformable image registration then adjusted manually. Tumor locations were integrated across all frames and displayed as heatmaps representing location probability. To determine individualized motion, a baseline contour representing average tumor rest position was expanded both isotropically and directionally in 1 mm increments in a novel analysis to define the contribution of each increment on target coverage. To assess directional dependence, displacements from rest position were evaluated in 4 planes from centroid: (A) 12 o'clock (OC) to 6OC (capturing volumetric shift in a portion of superior, posterior and inferior directions), B) 3OC-9OC, C) 6OC-12OC, D) 9OC-3OC. Histograms demonstrating the proportion of scan time the tumor was within expansions were generated, with expansion margins for 25%-95% coverage analyzed by patient. Wilcoxon-rank-sum test was performed to compare motion by site. Motion was evaluated in 66 patients (LH n = 27, OP n = 39). In LH, a median (med) isometric expansion of 8.5mm to achieve 95% target was required, with large variations observed for minimum (min): 2.8mm and maximum (max):23.5mm. Smaller differences were observed for OP with med of 5.3mm, (min:1.9mm, max:14.6mm). At 75%, 50% and 25% coverage, expansions for LH (med: 4.8 min: 1.9 max: 17.3; med: 3.8 min: 1.2 max: 12.9; med: 3.3, min: 0.6, max: 9.3) were not significantly different than OP (med: 3.8, min: 1.7, max: 10.9; med: 3.1 min: 1.3, max: 9.4; med: 2.1, min: 0.7, max: 8.4), suggesting larger but infrequent shifts in LH. Directional tumor displacement varied widely (Table 1), and by site and points describing the need for personalized margins. Current literature as well as the analysis in this study indicate a wide range of motion - both in magnitude and duty cycle - between and within HN sub-sites not captured on CT simulation. Moving forward, motion based heatmaps based on MR-cine may serve as visualization tool for ITV contouring or to generate personalized motion margins.

Evaluating the Use of SGRT and Abdominal Compression Device for Improved Patient Positioning in Liver Cancer Radiotherapy

To mitigate tumor displacement caused by respiratory movement and to enhance positioning accuracy in liver cancer patients during radiotherapy, abdominal compression fixation devices are commonly employed. However, the efficacy of using surface guided radiotherapy (SGRT) to further improve patient setup accuracy in combination with abdominal compression has not been fully established. Hence, we aimed to investigate this in our study. In this study, we analyzed data from 11 patients with liver cancer. The patients were positioned using isocentric skin markers and the abdominal compression fixture was placed on an accurate scale reading based on the records from CT simulation. A cone-beam CT (CBCT) scan was performed to assess setup errors. These setup errors represent data for the control group - Skin marker group. The patients were then adjusted to the correct treatment position based on CBCT correction and the SGRT system was activated for monitoring. Care was taken for the region of interest drawn to avoid the abdominal compression device for all patients. The reference surface used for monitoring was the captured VRT surface rather than DICOM. The six degrees of freedom values detected by the SGRT system were recorded, representing data for the test group - SGRT group. Both sets of data were analyzed using statistical software. The errors were presented as median (interquartile range) and the differences between the two groups were tested using paired Wilcoxon rank sum test, with P < 0.05 considered as significant. A total of 60 CBCT images were analyzed, the median values and interquartile ranges are presented in the Table. The results showed that the accuracy of the SGRT group in the x and y directions was significantly better than the skin marker group (P < 0.05). The median values for the x (transverse) direction were 0.25(0.09-0.43) cm and 0.09(0.05-0.19) cm for the skin marker and SGRT groups, respectively. The median values for the y (longitudinal) direction were 0.54 (0.29-0.79) cm and 0.14 (0.07-0.24) cm for the skin marker and SGRT groups, respectively. The results for the z (vertical) direction, Rz (rotation), Ry (roll) and Rx (pitch) rotation directions were also analyzed similarly. The findings of this study suggest that compared to skin markers, SGRT can improve the accuracy of patient positioning in liver cancer radiotherapy with abdominal compression, potentially reducing unnecessary radiation exposure from CBCT imaging due to inaccurate positioning. Further multicenter prospective clinical trials are required to confirm these results.

Weekly Image Guidance in Patients with Cervical Cancer Treated with Intensity Modulated Radiation Therapy: Results of a Large Cohort Study

Given the motion of the cervix, uterus, and organs at risk, image guidance is recommended for patients undergoing intensity modulated radiation therapy (IMRT) for cervical cancer. However, daily image guidance can be resource intensive, particularly in developing countries. In this study, we evaluated the feasibility of a weekly image-guidance pattern and analyzed the long-term outcomes in a large cohort of patients. The study enrolled patients with stage IB-IVA cervical cancer who received concurrent chemotherapy between 2005 and 2015. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam CT scans for image guidance. Following the image guidance, physicians would advise patients on the suitability of rectum and bladder preparation to help them prepare on non-imaging days. When significant tumor regression was observed, a second CT simulation and re-planning were performed. Intracavitary brachytherapy was delivered at a dose of 30 Gy in 5 fractions. The concurrent chemotherapy regimen consisted of weekly cisplatin. A total of 1,433 patients were included in the study. The median follow-up periods for all patients and surviving patients were 63 months (ranging from 2 to 125 months) and 70 months (ranging from 3 to 125 months), respectively. The 5-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates were 79.6%, 73.2%, and 86.5%, respectively. The estimated 8-year OS, DFS, and LC rates were 75.6%, 69.2%, and 85.2%, respectively. For patients with stage IB1, IB2, IIA, IIB, IIIA, IIIB, and IVA diseases (according to the 2014 FIGO staging system), the 5-year OS and DFS rates were 90.2% and 86.7%, 95.1% and 86.5%, 87.9% and 79.8%, 82.2% and 75.5%, 64.3% and 58.2%, 61.8% and 57.4%, and 43.8% and 19.4%, respectively. For patients with squamous cell carcinoma and adenocarcinoma, the 5-year DFS rates were 75.1% and 57.3%, respectively. For patients with positive regional lymph nodes, the 5-year OS and DFS rates were 64.1% and 57.8%, respectively. A total of 66 patients (4.6%) experienced grade 3-5 chronic toxicities, including 38 patients (2.7%) with gastrointestinal toxicities and 36 patients (2.5%) with genitourinary toxicities. IMRT with weekly image guidance resulted in high survival rates and acceptable toxicities. This indicates that weekly image guidance is acceptable in countries with limited medical resources.

Proton Online Adaptation Using Novel Cone-Beam Computed Tomography System

Cone beam computed tomography (CBCT) has been used in clinic frequently to provide quick, online, and handy three-dimensional images. However, due to its significant artifacts and inaccurate Hounsfield values (HU), CBCT based online proton adaptation is infeasible. Recently, a novel in-room imaging solution was developed to allow larger images, better contrast and faster CBCT imaging acquisition. Our work demonstrated for the first time the feasibility of using this novel CBCT images for direct intensity modulated proton planning. Three patients and three CIRS phantoms were scanned using novel imaging technique (CBCTp) for this work. CT curves were acquired by scanning a CIRS electron density phantom. Stopping power ratio was computed using the stoichiometric method. Proton plans were made on treatment simulation CT and further evaluated on CBCTp to compare the differences. The table below shows three patients and three phantoms plan comparisons. Multiple sites and dose levels were studied. The planning target volume (PTV) coverage (D95%) and mean dose difference between simulation CT and CBCTp are 0.8% and 0.3%, correspondingly. Dosimetrically, phantom and patient plans are almost identical between two imaging techniques. Lung patient plan show the largest variation due to patient tumor change and the quality of breathing. The novel and high quality of CBCT is feasible for direct proton planning with accurate CT calibration. It provides a reliable alternative solution for proton online adaptive therapy.

Non-Animal Stabilized Hyaluronic Acid (NASHA) Gel Marker vs. Surgical Clips for Tumor Bed Delineation in Breast Cancer Using MR-Simulation

Consistent delineation of the tumor bed (TB) after breast conserving surgery (BCS) is critical and remains a challenge with increasing prevalence of oncoplastic surgeries. Clips are generally used to help TB identification on CT-simulation but they are not well identified on MR-simulation. The aim of this study is to assess whether the use of NASHA gel with MR-simulation yields similar interobserver variability (inter-OV) compared to clips with CT-simulation. This prospective single arm feasibility study included patients eligible for BCS. After lumpectomy, the surgeon placed both clips (>5) and NASHA gel drops as markers to define the TB. Patients underwent CT and MRI simulation scans. Five radiation oncologists and one radiologist delineated the TB aided by clips on CT, and gel on MRI. The observers also assessed the visibility and utility of the gel (scale from 1 to 10), as well as the cavity visualization score (CVS, scale from 1 to 5). The primary endpoint was the inter-OV of the delineated TB using the overlap difference of contours using clips and CT versus gel and MRI, with the conformity index measured according to the pair definition of the Dice Similarity Coefficient (DSC). Of the 35 patients recruited, 30 were eligible for inter-OV analysis of TB delineation and 5 patients required further breast surgery for positive margins. One third of the eligible patients underwent an oncoplastic procedure. There were no significant differences between inter-OV of delineated TB using clips and CT versus gel and T2-weighted MRI with the mean DSC (0.60 vs 0.62, p = 0.364). The observers reported higher usefulness of gel in patients with an oncoplastic procedure than not (median US 8.2 vs 6.6, p = 0.024), and higher visibility of gel in patients who had their scans within 6 weeks than beyond post-op (median VS 8.1 vs 6.1, p = 0.013). When the CVS was higher (3-5), the median US of gel was lower (5.9 vs 7.8, p = 0.004), and the conformity index of clip and CT delineated TB was higher (median DSC 0.72 vs 0.53, p <0.001). Interestingly, a higher CVS did not lead to significantly higher conformity index of gel and T2-weighted MR delineated TB (mean DSC 0.67 vs 0.58, p = 0.073). NASHA gel injection added a median of 3 minutes to the operating theatre (OT) time and was rated as 'easy' in 89% of cases by surgeons. There were no immediate adverse events (AE) in OT, while 2 of 35 patients later experienced a grade 3 AE - hematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS and axillary dissection. These reflect common risks with standard BCS and are not clearly attributed to gel injection alone. Use of NASHA gel leads to similar inter-OV of BC TB delineation compared to >5 clips. NASHA gel is hence a reliable alternative to clips when MR-simulation is used.

Quantifying the Dosimetric Impact of Tissue Hounsfield Unit Assignment in Deep Learning-based Synthetic CT Images For MRI-Only Radiation Therapy of The Head and Neck

MRI-only simulation for head and neck (HN) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic CTs (sCTs) are generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCTs. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning. In this study we quantify differences in Hounsfield Unit (HU) values between paired CT/ sCTs of HN cancer patients and investigate the dosimetric impact on clinical treatment plans. Fourteen patients with head and neck cancer undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRIs were deformed to the CT using multimodal deformable image registration. SCTs were generated from T1w DIXON MRI using a commercially available deep learning-based generator (MRIplanner, Spectronics). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (<-250HU), adipose tissue (-250HU to -51HU), soft tissue (-50HU to 199HU), spongy (200HU to 499HU) and cortical bone (> 500HU) were quantified. T-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference >70HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical IMRT treatment plans created on CTs were retrospectively recalculated on sCT images using compared using the gamma metric. The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7±0.3, 1.1±0.1, 1.0±0.1, 0.9±0.1 and 0.8±0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t = 0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences > 70HU were the L/R cochlea and mandible, occurring in >78% of the tested cohort. These structures contain dense bone/air interfaces. Plans recalculated on sCTs yielded global/local gamma pass rates of 98.7%±1.2% (3mm,3%) and 95.5%±2.5% (1mm,1%). Mean differences in D95, D50, D10 and D2 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTV) were 0.8%±1.5% and 2.1% ± 1.2% respectively. In this cohort, HU differences in sCTs were observed but did not translate into a reduction in gamma pass rates and OAR/PTV DVH metrics. The acquisition of additional training data such as ultrashort echo time MRI could improve bone/air contrast and reduce bone/air sCT misclassifications. Further studies will establish the variation in sCT dosimetric accuracy using a larger retrospective cohort to inform QA limits on clinical sCT usage.

Dosimetric Validation of 3D-Printed Bolus at Different Printing Infill Percentage in VMAT Plan

The 3D printed bolus technology is rapidly evolving in external beam radiotherapy and printing parameters can have a significant impact on absorbed dose. In this study, a novel 3D printed bolus was designed to evaluate the time and material cost effects, dosimetry differences, and surface dose modulation capabilities in the volumetric-modulated arc therapy (VMAT) plan at different print filling percentages. A hollow-type bolus, the middle 2.36 mm of 5 mm thickness infilled with different ratio, was designed and printed with polylactic acid (PLA). The ratio of printed material was defined by the infill percentage parameter ranging from 10% to 90%. For each bolus, two treatment plans were designed with AAA algorithm, considering the real computed tomography (CT) scan of the 3D printed bolus and modeling the 3D printed bolus as a virtual bolus structure. Percentage depth dose (PDD) profiles were calculated to build up the mapping equivalent CT value in treatment plan system (TPS). Measurement dose was performed by radiographic films. The PDD profiles were then compared between measured and calculated. A simulation VMAT treatment plan with planning target volume (PTV) close to the body surface was designed on a water-equivalent phantom, and the modulation capabilities of epidermal dose under different filling percentage was compared. Compared with 100% percent infill 3D printed bolus, The maximum printing time could be reduced by 47.8% and material consumption could be reduced by 42.5%. The surface dose at single field irradiation can reach 69.6% to 85.8% of the maximum dose in different filling boluses. The PDD measurement and mapping equivalent CT calculation deviation was less than 3% when the infill percentage of the middle region is greater than 30%. The dose distribution of the VMAT plan is satisfying for infill percentages greater than 30%. Using the 3D printing technology is possible to modulate the amount of shift of the build-up region by tuning the infill percentage of the 3D printed bolus. Patients could undergo CT simulation without bolus. Appropriate bolus could be selected according to the location of the PTV region and dose requirement.

Pelvis Treatment Plan Dose Comparison for Proton Therapy Using Single Energy and Dual Energy Computed Tomography Simulation Methods

In proton therapy, plan robustness is ameliorated by expanding the irradiation volume beyond the target, in order to mitigate setup and proton range uncertainties (RU). A byproduct of this expansion is elevated doses to surrounding organs at risk (OARs) which reduce some of the benefits associated with proton therapy. Dual-energy CT (DECT) has been shown in multiple phantom and animal tissue studies to reduce RU without compromising plan robustness. This study quantifies dosimetric differences between single-energy CT (SECT) and DECT for pelvis patients treated with intensity modulated proton therapy (IMPT). Under IRB approval, SECT and DECT scans from 25 IMPT pelvis patients were acquired using a CT scanner. Clinical plans were generated on the SECT images using robust optimization settings of 3.5% RU and 5 mm setup uncertainty in a treatment planning system. Subsequently, the clinical plans were recomputed on the corresponding DECT generated SPR-map images. For each patient, target coverage, mean and maximum OAR doses were compared for both image sets. Comparison of two plans showed systematic differences in target minimum dose (D99%) and V100%. Variations as high as 3.1% with DECT were observed in D99% indicating target under-dosage. On average, use of SECT overestimated V100% by 2.4% when compared to DECT. Since all clinical plans were optimized robustly to meet V95% coverage, higher agreement (<1%) was achieved for V95% (99.9±0.2%), and D95% (99.6±0.3%). DECT relative to SECT indicated slightly higher OAR maximum doses for femoral heads (2.3±2.78%), penile bulb/external genital (1.33±4.00%) and large bowel (0.5±1.25%). Similarly, higher mean dose was observed to rectum (2.08±4.88%), bladder (1.41±0.25%), femoral heads (1.18±6.61%) and penile bulb/external genital (1.78±5.74%) for DECT relative to SECT. Our results show a disparity between evaluated SECT and DECT target and OAR dosimetric parameters. Given the higher accuracies in proton range estimation associated with the use of DECT, its use can imply a potential for more conformal proton plans as well as higher TPS computed target coverage and OAR dose accuracy, both of which enhance overall treatment quality.

Simulation CT Features and Radiation Cardiotoxicity in Non-Small Cell Lung Cancer

Radiation cardiotoxicity is a significant clinical dilemma in non-small cell lung cancer (NSCLC) radiation therapy (RT). Baseline cardiovascular (CV) status may influence the risk of cardiotoxicity, and may be ascertainable from the appearance of the heart on simulation computed tomography (CT). We examined the association of CT features with incidental heart dose and risk of cardiac events in NSCLC. Patients treated with curative-intent RT between 2015 and 2020 at a regional center were identified. Clinical notes were interrogated for baseline patient and CV health details, and follow-up CV events. Cardiac events were verified by a cardiologist. A deep learning-based auto-segmentation tool was applied, allowing extraction of a pre-specified list of volume parameters in a programming environment. CAC was graded as none, mild, moderate and severe in patients with a non-contrast scan. The craniocaudal relationship of the PTV and heart (Feng atlas) were annotated. A total of 478 patients were included, with a median age of 70 and Charlson Index of 5. The median mean heart dose was 6.3 Gy (IQR 2.7-11.4). The median lung V20 was 20.0% (IQR 14.8-27.1). Cardiovascular risk factors were common, with most patients having 2 (39%) or 3 (31%). A history of previous cardiac events was common, including myocardial infarction (14%), arrhythmia (11%) or heart failure (9%). A total of 6.9% and 7.1% patients developed a new atrial arrhythmia (AA) or heart failure (HF) after completing RT. The volume metrics with the highest AUC for AA and HF events were the left atrium (LA) (AUC 0.67, p = 0.0002) and left ventricle:right ventricle (LV:RV) ratio (AUC 0.66, p = 0.0021). Kaplan-Meier analysis for cardiac events dichotomizing at the optimal cut-point for maximum sensitivity and specificity demonstrated significantly different rates for both AA (LA 109cc, HR 3.35, 95% CI 1.64-6.83, p = 0.0009) and HF (LV:RV ratio 1.61, HR 2.37, 95% CI 1.19-4.74, p = 0.0143). Only 2 patients with non-contrast scans developed a myocardial infarction, both had mild CAC. The incidence of pooled cardiac events was not significantly different between patients with no (n = 2/21, 9.5%), mild (n = 10/38, 26.3%), moderate (n = 8/53, 15.1%) and severe (n = 7/24, 29.2%) CAC (p = 0.3916). Where the inferior border of the PTV was above the superior border of the heart, mean heart dose was significantly lower than compared with overlap of levels (1.9 Gy v 9.7 Gy, p<0.0001), and this was true for 3DCRT (n = 139, p<0.001), IMRT (n = 94, p<0.001) and VMAT (n = 145, p<0.001) patients. LA volume and LV:RV volume ratio are predictive for the development of AA and HF respectively. CAC grade did not differentiate patients by risk of cardiac events. Where the craniocaudal level of the PTV doesn't overlap with the level of the heart, the cardiac dose is likely to be very low. Several simulation CT features are associated with cardiac events following treatment for NSCLC and prospective evidence of cardiac risk could enable medical optimization prior to RT.

Inaugural Experience with Real-time Gated Liver Proton SBRT and Treatment Plan Quality Improvement

DIBH SBRT is routinely used for liver proton therapy. While intra-fraction target motion is limited with DIBH, acquisition of DIBH CT simulations in triplicate, as is done at our institution, reveals that variation does exist between each DIBH scan. The related target position can also vary correspondingly. The most common setup uncertainty for robust proton SBRT liver plan used at our institution is 5 mm sup-inf (SI) and 3 mm radially. Real-time gated proton therapy (RGPT) has the potential to provide instantaneous feedback for intra-fraction target motion to maximize patient safety and inform optimal treatment planning. Our first RGPT liver SBRT with intra-fraction motion under deep inspiration breath hold (DIBH). The potential treatment plan quality improvement brought by RGPT is investigated. The following metrics were used in establishing our RGPT proton DIBH SBRT liver program: the iso center is always set at the fiducial mark; the beam orientation is selected to achieve both good plan quality and tracking performance; daily CBCTs are acquired and verified using fiducial maker position with kV images; robust uncertainty is determined by the gating tolerance; SBRT plan has three beams with uniform dose. Target motion was monitored throughout treatment. To evaluate dose sparing for surrounding OARs, a plan with tighter gating tolerance (3 mm SI and 2 mm radially) is optimized for dosimetric comparison. Statistical analyses were conducted using a programming environment. Each of the three proton beams were delivered using DIBH over a total of 120-140 seconds. The average beam on time were 61.4, 66.9 and 62.8 seconds. The intra-fraction motion showed that targets could move up to 3 mm within the same DIBH. The motion increased with time. The table details the mean, maximum, standard deviation, and estimated upper 95% of directional shifts for three beams. Based on these results, plan delivery efficiency was maintained even with tighter gating tolerance. The comparison plan with tight gating tolerance showed significantly less dose (-25%) to the stomach in coronal view. RGPT successfully tracked fiducial marker motion for DIBH SBRT liver treatment. Despite target drift during DIBH, the uncertainty of our DIBH SBRT procedure was sufficient to cover target motion throughout treatment. Based on the target drift value, a maximum of 25 seconds for breath hold time should be employed. Utilizing a tighter gating tolerance of 3 mm SI and 2 mm radially has the potential to maintain target coverage while significantly reducing OAR dose. Aggregated RGPT-derived data may provide optimal treatment planning parameters such as variable uncertainty based on target location.

The Feasibility of Adaptive CT Simulation-Free Radiation Therapy

To investigate the feasibility of a novel, streamlined radiotherapy treatment workflow in which simulation and treatment occur in a single on-table session. The efficiency, dosimetric accuracy, plan quality, and resource requirements were metrics used to evaluate the clinical potential of CT simulation-free radiotherapy. An adaptive radiotherapy treatment platform was upgraded to include a novel CBCT system reporting image quality and Hounsfield unit accuracy specifications comparable to standard fan-beam CT. An in-house workflow was designed to allow the CBCT data to be used as reference image sets for planning. Two test cases were completed on anthropomorphic phantoms equipped with small volume ion chambers (cross-calibrated to an ADCL traceable dose standard) to evaluate the feasibility and accuracy of the workflows. A spine was planned for palliative treatment with 8 Gy in 1 fraction, and an intact prostate was planned for definitive treatment with 60 Gy in 20 fractions. The CBCTs were acquired using default thorax and pelvis imaging protocols and reconstructed using an iterative algorithm with scatter removal. CBCTs were used for contouring and planning, and treatment was delivered via an online adaptive workflow. An extended-field CBCT acquisition can be acquired in 12 s of acquisition time and reconstructed in approximately 1 min. The superior-inferior extent for the CBCT planning images was 42 cm, which captured the full extent of relevant anatomy; an audit of recent single-site palliative CT simulation scans had an average length of 44.9 cm. The contouring and treatment planning for the spine and prostate were completed in 30 min and 23 min, respectively. The dosimetric agreement with the treatment plan agreed to within a range of -1.17 to 1.64%, and a mean and standard deviation of 0.41 ± 1.16%. Using an in-house workflow, CT simulation-free radiation therapy was shown to be feasible with acceptable workflow efficiency and dosimetric accuracy. This approach may be particularly applicable for urgent palliative treatments. With the availability of software to enable this workflow, and the continued advancement of on-treatment adaptation, single-visit radiation therapy may replace current practice for some clinical indications.

ACR Accreditation of a Novel Linac-Based kV-CBCT System on a High-Speed Ring-Gantry

An advanced kV-CBCT imaging system mounted on a high-speed ring-gantry Linac has recently been introduced, offering improved imaging hardware and reconstruction software to produce high quality CBCT images usable for treatment planning. Imaging performance of the system was assessed using the American College of Radiology (ACR) accreditation designed for diagnostic CT systems, additionally comparing its results to pre-existing diagnostic CT and Linac-based CBCT systems. All imaging protocols on the novel imaging system were scanned with the ACR head phantom and evaluated using ACR recommended testing and passing criteria. ACR image quality parameters include contrast-to-noise ratio (CNR), spatial resolution, HU accuracy, image scaling, and HU uniformity. CNR ≥1.0 for adult head and body, ≥0.7 for pediatric head, and ≥0.4 for pediatric body imaging protocols pass ACR criteria. Spatial resolution ≥6 line-pairs/cm for head and ≥5 line-pairs/cm for body protocols pass ACR criteria. HU accuracy passing criteria includes acrylic (110 to 135 HU), air (-1005 to -970 HU), bone (850 to 970 HU), polyethylene (-107 to -84 HU), and water (-7 to 7 HU). Image scaling measurements with errors ≤5% and HU uniformity maximum differences ≤5 HU pass ACR criteria. For machine cross-comparisons, adult Head and Pelvis imaging protocols were acquired on an existing diagnostic CT and 2 Linac-based CBCT systems (1 traditional C-arm and 1 ring-gantry) and analyzed with the same ACR methodology and passing criteria, with passing rates compared. On the novel imaging system, all standard patient size imaging protocols using 125 kVp (Head, H&N, Thorax, Thorax Slow, Breast, Abdomen, Pelvis, Pediatric Head, and Pediatric Abdomen) passed all ACR criteria; while 2 larger patient focused imaging protocols using 140 kVp (Abdomen Large and Pelvis Large) produced minor deviations on HU uniformity (maximum differences of 5 - 7 HU) but passed all other ACR criteria. The novel system matched passing rates of a diagnostic CT simulator, and outperformed pre-existing Linac based CBCT imaging systems. This newly developed advanced imaging system produces high quality images, meeting diagnostic CT ACR recommendations and far surpassing the CBCT image quality currently available on pre-existing Linacs.

An In Silico study of a One-Day One-Machine Workflow for Definitive Radiotherapy Cases on a Novel Simulation and Treatment Platform

The workflow in Radiotherapy (RT) has largely unchanged for the past three decades, despite increasing evidence suggesting that delayed access to RT, including the wait time between consultation, simulation, and treatment appointments, can negatively impact clinical outcomes. In this pilot study, we present preliminary results of an in silico study that demonstrate the feasibility of a novel RT platform, which integrates simulation into the treatment process and enables patients to receive immediate RT after their initial RT consultation. A prospective clinical study has been approved to assess the capabilities of a novel RT platform with a high quality CBCT system for imaging guidance as well as planning. This new platform enables a novel clinical workflow that allows clinicians to review contours and plans created on diagnostic CT images prior to the initial RT consultation and allow them to approve new plans adapted on the actual simulation dataset acquired on the first treatment fraction. Four patients receiving standard of care RT (three abdomen and one thorax) consented for this study and underwent additional experimental CBCT simulation on the new platform in addition to their standard CT simulation. The CBCT simulation was taken in two setups: with a specific mold on a flat couch and without a mold on a curved couch. To demonstrate the equivalence of the new workflow to the current standard of care, the plan created on the most recent diagnostic CT images was compared to the plans adapted on the experimental simulation images and the standard CT simulation images, using a knowledge-based model. Contours were propagated from approved datasets to the new datasets through deformable image registration. All experimental simulations were completed between 14 and 21 minutes with the assistance of two therapists. The contouring, editing, and replanning process took less than one hour in all cases, in line with our experience and peer-reviewed literature. Despite notable anatomical changes observed, the dose-volume histograms (DVH) were consistent, as shown in Table 1. The novel workflow presented herein was feasible and demonstrates that the integration of simulation with image-guided RT on one single platform may unlock the potential of accelerating the RT workflow and reducing the wait time for treatment from weeks to hours.

Optimization of Workup Pathways to Decrease Radiotherapy Wait Times and Improving Patient Experience: A Single Centre Study

Wait-times are challenging for certain radiotherapy (RT) centers, and benchmarking is challenging, given the different standards used. Beyond the standards of referral to consult and consult to treatment, certain centers have established a "ready-to-treat" (RTT) definition to address the reality of patients requiring further investigations from consult to enable a treatment plan. In this single RT center study, a Timely Access and Patient Support (TAPS) model of care has been implemented aiming to improve access to care and, ultimately, patient outcomes. Thiscomparative cohort study was conducted in a single mid-size RT center serving mainly rural communities as part of a larger multi-center academic institution. In collaboration with a Radiation Oncologist (RO), the TAPS clinic is run by a Nurse Practitioner who provides patient assessment and submits requisitions to ensure the patient has support services and is RTT by the time of RO consult. All newly suspected/diagnosed adult cancer patients referred to the center with a triage priority of ≥2 weeks were eligible. Non-metastatic breast and prostate cancers were excluded. Retrospective and prospective data were collected from patient medical records, and descriptive statistical analysis was performed. Pre- and post-TAPS clinic comparison was made for wait times and patient-reported outcomes (PROs) using the Edmonton Symptom Assessment System-revised. During the first 6 months of the study, 66 eligible patients were assessed in the TAPS clinic, prompting 177 orders including referrals (52%) (top 3: social worker 30%, dietitian 20%, and cancer patient navigator 11%), investigations (27%) (top 3: CT 21%, MRI 19%, and biopsy 25%), and interventions (21%). The most common cancers were thoracic (33%), GI (23%) and head and neck (14%). The mean wait time from referral to TAPS consult was 5 days compared to 15 days for pre-TAPS patients to be seen in RO consult. The mean wait time from referral to RTT was 33 days VS 40 days in the post- VS pre-TAPS setting.71% of post-TAPS patients were RTT at RO consult compared with 43% pre-TAPS. Post-TAPS patients reported less fatigue and anxiety and better overall well-being during CT simulation compared to pre-TAPS patients. Preliminary data of TAPS clinic implementation has shown the potential to positively impact RTT times and PROs for psychosocial distress by the time of RT planning. This data also sheds light on the topic of wait time definitions, the investigations required before RTT and the potential role of physician extenders within the health care team to facilitate accelerated workup of malignancies. While TAPS study data will help to inform local cancer care program operations, it is also considered relevant to the broader RT community and professional RT societies addressing standards related to RT access.

The Role of Coronary Artery Calcium Score to Assess Risk of Cardiovascular Disease in Irradiated Esophageal Cancer Patients

Coronary artery calcium (CAC) score is an important predictive imaging marker of cardiovascular disease (CVD). While studies have found positive association between CAC score and cardiac toxicity in irradiated lung and breast cancer patients, there are no studies assessing CAC scores in esophageal cancer (EC). While a cardiac-gated CT is required for standard Agatston CAC score, visual assessment of CAC via ordinal scoring on non-gated CT has shown good concordance with Agatston score. In this study, we sought to examine whether visual assessment of CAC, measured on standard of care, non-contrast chest CT, predicts the development of adverse cardiovascular events (ACVE) in irradiated EC patients. This is a single institution retrospective study of EC patients treated with RT from 2010-2021. We included patients with available PET/CT at diagnosis or chest CT simulation scan without contrast, and excluded those with history of percutaneous coronary intervention, coronary bypass surgery, or prior thoracic RT. Pre-treatment characteristics, clinical factors, and grade ≥ 3 (G3+) adverse cardiovascular events (ACVE) (CTCAEv5.0) were evaluated. Visual assessment of CAC was performed using ordinal method (CAC scored from 0 to 12), by a thoracic radiologist. Fine and Gray regression was used to compute hazard ratios for time to first ACVE. Univariate analyses using Cox proportional hazards were used for overall survival (OS). ACVEs were recorded from start of oncologic treatment and OS calculated after completion of RT. A total of 118 patients were analyzed with a median follow-up of 16 months. Median age was 67 years, 65% male, 43% white, 59% with EC of distal esophagus, and 59% had squamous cell carcinoma. Median mean heart dose was 21.93 Gy (range 0.15-36.94). 24% developed G3+ ACVEs: atrial fibrillation 9%, stroke 6%, heart failure 4%, pulmonary embolism 4%, pericardial effusion 3%, myocardial infarction 2%, heart block 2%, and cardiac death 1%. On univariate analyses, CAC >1 vs. CAC ≤ 1 trended towards increased risk of ACVE (HR = 1.95, 95% CI = 0.89-4.26; p = 0.094), however it is not predictive of OS (HR = 1.31, 95% CI = 0.75-2.30; p = 0.343). Proportion of patients with ACVEs was greater in CAC>1 group (Table). When compared to patients with CAC ≤ 1, those with CAC >1 were older (median age 62 vs 72 years, p = 0.0015), less likely to be never smokers (38% vs 30%, p = 0.0437), and more likely to have hypertension (43% vs 64%, p = 0.0197), and hyperlipidemia (30% vs 47%, p = 0.0557). This is the first study to investigate the relationship between CAC score and ACVEs in EC. While the study was underpowered (likely due to low rates of recorded ACVEs), to detect a significant association between CAC score and ACVEs, there was a trend towards increased risk of ACVEs in patients with a CAC score >1 by visual ordinal scoring. Further prospective evaluation with a larger cohort is warranted.

Evaluation of Sexual Side Effects in Patients after Chemoradiation and Brachytherapy for Gynecologic Cancers Involving the Lower Vagina and Bulboclitoris

Radiation toxicity to the bulboclitoris has not been previously investigated. This retrospective cohort study aims to report sexual side effects of patients who underwent radiotherapy for tumors involving the lower vagina, periurethra, and bulboclitoris (BC). Patients treated between 2017- 2022 for gynecologic cancer involving the low vagina were included. The high-risk clinical target volume (HR-CTV), bladder, rectum, and urethra were contoured on patient imaging during initial treatment planning. The BC was retrospectively contoured using T2 MRI sequences fused to the pre-treatment and brachytherapy CT simulation. Superiorly, the BC was defined as inferior to the pubic symphysis and attached to the suspensory ligament of the clitoris. Laterally, the crura extend on either side of the corpus. Inferiorly, the vestibular bulbs flank the urethra and vagina on either side, extending posteriorly to mid-vagina. Dosimetric data for the BC, vaginal morbidity using the CTCAE 4.0 for vaginal stenosis, and pain scoring of the BC were obtained via chart review. Patients underwent external beam radiotherapy (IMRT) to the pelvis and bilateral inguinal region (45 Gy in 25 fractions) followed by High Dose Rate Ir-192 interstitial brachytherapy in 5 fractions for a total dose of 25 Gy (22.5 - 27.5 Gy). Patients had a median age of 65 years (49-73) with tumors located in the lower vagina, near the BC and urethra. At the time of brachytherapy, in order to cover the HR-CTV, interstitial brachytherapy needles were placed within the BC structure with 58% (33% - 77%) of total interstitial needles placed within the bulbs of the BC. The mean pre-treatment volume of the BC was 16.6 cc (11.9 - 20.9 cc) and at brachytherapy was 12.66 cc (7.3 - 22.1 cc) with Table 1 summarizing radiation doses. At a median follow up of 19.6 months, all patients had a complete local response, with one patient deceased of metastatic disease. In the acute period, all patients reported severe pain in the clitoral glans region and dysuria that completely resolved after 2 years. Grade 1-2 vaginal stenosis occurred in all patients despite vaginal dilator usage. One patient reported decreased clitoral sensitivity and inability to achieve clitoral-mediated orgasm 5 months after radiotherapy. This study demonstrates that the BC receives a significant radiation dose during vaginal brachytherapy treatment which can cause clitoral pain and dysfunction. Further studies are needed to evaluate the dose response of the BC as well as explore methods to spare the organ during radiation therapy in order to minimize toxicity and preserve sexual function.

High-Dose-Rate Brachytherapy for Vaginal Rhabdomyosarcoma (RMS): Lessons Learned at a Single Institution

Botryoid RMS is a rare pediatric tumor most commonly arising within the vaginal wall of girls under age three. Most patients are successfully treated with low-risk chemotherapy protocols but local treatment is required to minimize risk of local relapse. Intravaginal brachytherapy is an effective local therapy that can minimize sequelae in these very young patients. We reviewed records of all patients with RMS who received intravaginal high-dose-rate brachytherapy from 2010-2022 at a single institution. All were treated with multiagent chemotherapy with or without minor surgical procedures, and had no gross disease prior to intravaginal brachytherapy. All patients underwent CT simulation under anesthesia and optimal-sized cylindrical applicators were chosen based on patient anatomy. Twelve girls, median age 23 months (range 3-33), were treated with daily anesthesia. All were Stage 1 and 92% had Group III disease. A single patient had Group IIA disease based on up-front resection. Early in the series, 5 patients received 21 Gy in 7 fractions according to COG protocol guidelines. Subsequent patients received higher doses of 28-30 Gy in 7-10 fractions. Custom sized cylinders were used with diameters ranging from 1.2-1.6 cm and dose was prescribed to a median depth of 3 mm. Median mean dose to the rectum, bladder, uterus, and bilateral ovaries was 8.7 Gy, 7.2 Gy, 6.9 Gy, and 5.0 Gy, respectively. Median follow-up was 4 years (range 1-10). No acute or late side effects have occurred. At follow-up, three girls were of pubescent age, all three exhibited signs of puberty and two had reached menarche. Three girls (25%) suffered local relapse at a median of 15 months (range 5-16 months) after brachytherapy. One-year and five-year local control rates were 92% (95% CI 54-99%) and 70% (95% CI 32-89%), respectively. All relapses were in patients receiving 21 Gy and two were beyond full dose coverage of brachytherapy at the introitus and in the uterus. Subsequent patients receiving higher doses and full coverage of the vagina have had no local failures. Two of three patients who failed were cured with salvage therapy resulting in one-year and five-year overall survival rates of 100% and 86% (95% CI 33-98%), respectively. Intravaginal high-dose-rate brachytherapy is an excellent option for local control of vaginal RMS with fewer long-term risks than external beam proton therapy or radical surgery. A dose of 28 Gy in 7 fractions prescribed to the entire vagina is necessary for optimal prevention of relapse. Longer follow-up is needed to confirm preservation of ovarian, reproductive, and sexual function.

Financial Implications of Evolving Breast Cancer Radiotherapy Treatment Protocols

Adjuvant radiotherapy for breast cancer represents a significant portion of radiotherapy (RT) treatments. The resource implications of evidence-based changes in treatment protocols must be defined to facilitate RT service planning. We designed a study to calculate the impact of past changes and create a model to allow prediction of costs implications for future changes. Changes in RT treatment (shown in table 1) in the past 3 years were identified in consultation with clinical staff and by reviewing institutional treatment guidelines. Resource and infrastructure costs were calculated for each protocol. Staff time was calculated using standard time slots where known (e.g., CT simulation appointment) and estimates based on discussion with staff (e.g., time to plan whole breast RT). Cost / Gy was calculated based on Linac cost of €2.5M, 10% annual service charge over 12-year lifetime, 2.7 patients treated / hour (verified institutional metric) and standard 2Gy fraction, giving €37.72 / Gy. We did not include facilities costs nor account for differing treatment outcomes. We collected relevant data on a consecutive 6-month sample (Jan - Jun 2019) of women receiving adjuvant RT for breast cancer (n = 224). Total costs were calculated by applying costs for each protocol change to the women in this cohort eligible for the changes. Protocol changes and costs are summarized in table 1. The use of DIBH for women <60 years receiving IMN RT (left and right sided) added a cost. The largest cost saving resulted from more selective tumor bed boost, a saving of €462,138. The potential impact of a 5-fraction boost for women with non-low risk DCIS was estimated. In the cohort analyzed, identified changes in adjuvant breast radiotherapy resulted in overall savings due to updated indications for boost and the implementation of ultra-hypofractionated radiotherapy. We are now analyzing the impact of introducing simultaneous integrated boost and partial breast radiotherapy.

Hippocampal Avoidance Whole BRAIN Radiotherapy (HA-WBRT) with Simultaneous Integrated BOOST (SIB) vs. HA-WBRT in Multiple Brain Metastases: A Dosimetric Comparison

There has been a paradigm shift in managing multiple brain metastases. Various options include SRS, WBRT, and WBRT with Hippocampal avoidance (HA-WBRT). There is no consensus for the treatment of multiple brain metastases (>3 brain metastases). A new technique that has proven feasible is dose escalation in the form of simultaneous integrated boost. The aim of this study was to compare the dosimetry parameters of HA-WBRT plus simultaneous integrated boost versus HA-WBRT alone in multiple brain metastases. In a prospective trial,16 patients with multiple brain metastasis (≥ 3) from various primaries with good performance scores (ECOG PS ≤ 2) are recruited. All patients underwent CT simulation (1.5 mm slice thickness) and RT plans for HA-WBRT with (SIB) and HA-WBRT alone were made. A 5 mm margin was given to the bilateral hippocampus for Hippocampal Avoidance. In the HA-WBRT plan for the PTV i.e., whole brain plus 3 mm margin minus hippocampal avoidance region (H.A.), a dose of 30 Gy in 10 fractions is prescribed over two weeks. In HA-WBRT with SIB, a dose of 30 Gy in 10 fractions over two weeks is prescribed for the PTV, which is the clinical target volume, minus the hippocampal avoidance region (H.A.) minus the PTV Mets (1 mm margin to the GTV). A simultaneous Integrated Boost of 42.5 Gy in 10 # over two weeks is prescribed for PTVmets. Planning was done using a VMAT technique with 6MV F.F.F. beam energy in a treatment planning software. The mean B/L hippocampus volume is 3.47 cc. The mean dose of PTV D98% in HA-WBRT plans is 27.45 Gy, whereas in HA-WBRT with S.I.B. is 27.36 Gy (p = 0.90). V30 mean dose in HA-WBRT plans is 93.35%, and the mean dose in HA-WBRT SIB is 91.87% (p = 0.12). PTV D2% mean dose in HA-WBRT Is 36.06 Gy, and in HA-WBRT -S.I.B., it is 40.58 (p< 0.001). The mean bilateral hippocampus Dmax in HA-WBRT is 14.85 Gy, and in HA-WBRT-SIB is 14.25 Gy (p = 0.35). The mean Bilateral hippocampus D100% is 9.14 Gy in HA-WBRT and 9.01 Gy in HA-WBRT-SIB (p = 0.54). The mean brainstem Dmax in HA-WBRT is 36.82 Gy compared to 38.55 Gy in HA-WBRT-SIB (p = 0.02). In patients planned for a simultaneous boost along with hippocampal sparing whole brain radiotherapy, the mean dose to the hippocampal region did not increase. The Dmax of Brainstem, optic chiasma is significantly higher in HA-WBRT-). Our study, the mean dose to PTVmets is more than 45 Gy and more than 50 Gy to GTV with a BED of more than 65 Gy (α/ß = 10) to the metastases, which is equivalent to some ablative dose regimens. Simultaneous integrated boost along with hippocampal sparing radiotherapy thus helps in sparing the hippocampus and delivering higher doses to the metastases and intermediate doses to the rest of the brain, addressing the microscopic disease.

Dosimetric Quality of Artificial Intelligence Based Organ at Risk Segmentation

to compare dosimetric parameters between Artificial intelligence (AI) generated organ at risks (OAR) and Radiation Oncologist approved OARs and evaluation of appropriateness unedited AI- OARs in routine clinical plan optimization and evaluation. The OARs (lung, spinal cord and heart) for twenty SBRT (stereotactic body radiotherapy) lung CT simulation datasets were derived by AI based segmentation algorithms. These AI- OARs were edited by a staff Radiation Oncologist and then subjected to our SBRT peer-review process at our institution. A SBRT plan based on the approved contours was created. Dosimetric parameters for the unedited AI-OARs and edited physician-approved OARs were then compared. Lung V20 differences between AI- OAR and physician- OAR varied from 0.01% - 0.7% with a mean value of 0.1% difference (p-value 0.004). Spinal cord D0.03cc varied from 0.02 Gy - 0.9 Gy with a mean value of 0.3 Gy difference (p-value 0.002). Heart D0.03cc varied from 0.01 Gy - 4.3 Gy with mean value 0.9 Gy difference (p-value 0.02). Dosimetric parameters for AI-based lung, spinal cord and heart OARs vs physician approved OARs were different, overall, the differences were generally small. These differences are likely on par with inter-observer differences seen between individual radiation oncologists. Unedited OARs have the promise for routine use in plan optimization and evaluation to further improve efficiency.