The impact of advancing the standard of care in radiotherapy on operational treatment resources.

PURPOSE: To demonstrate the impact of implementing hypofractionated prescription regimens and advanced treatment techniques on institutional operational hours and radiotherapy personnel resources in a multi-institutional setting. The study may be used to describe the impact of advancing the standard of care with modern radiotherapy techniques on patient and staff resources. METHODS: This study uses radiation therapy data extracted from the radiotherapy information system from two tertiary care, university-affiliated cancer centers from 2012 to 2021. Across all patients in the analysis, the average fraction number for curative and palliative patients was reported each year in the decade. Also, the institutional operational treatment hours are reported for both centers. A sub-analysis for curative intent breast and lung radiotherapy patients was performed to contextualize the impact of changes to imaging, motion management, and treatment technique. RESULTS: From 2012 to 2021, Center 1 had 42 214 patient plans and Center 2 had 43 252 patient plans included in the analysis. Averaged over both centers across the decade, the average fraction number per patient decreased from 6.9 to 5.2 (25%) and 21.8 to 17.2 (21%) for palliative and curative patients, respectively. The operational treatment hours for both institutions increased from 8 h 15 min to 9 h 45 min (18%), despite a patient population increase of 45%. CONCLUSION: The clinical implementation of hypofractionated treatment regimens has successfully reduced the radiotherapy workload and operational treatment hours required to treat patients. This analysis describes the impact of changes to the standard of care on institutional resources.

MRI-TRUS registration methodology for TRUS-guided HDR prostate brachytherapy.

PURPOSE: High-dose-rate (HDR) prostate brachytherapy is an established technique for whole-gland treatment. For transrectal ultrasound (TRUS)-guided HDR prostate brachytherapy, image fusion with a magnetic resonance image (MRI) can be performed to make use of its soft-tissue contrast. The MIM treatment planning system has recently introduced image registration specifically for HDR prostate brachytherapy and has incorporated a Predictive Fusion workflow, which allows clinicians to attempt to compensate for differences in patient positioning between imaging modalities. In this study, we investigate the accuracy of the MIM algorithms for MRI-TRUS fusion, including the Predictive Fusion workflow. MATERIALS AND METHODS: A radiation oncologist contoured the prostate gland on both TRUS and MRI. Four registration methodologies to fuse the MRI and the TRUS images were considered: rigid registration (RR), contour-based (CB) deformable registration, Predictive Fusion followed by RR (pfRR), and Predictive Fusion followed by CB deformable registration (pfCB). Registrations were compared using the mean distance to agreement and the Dice similarity coefficient for the prostate as contoured on TRUS and the registered MRI prostate contour. RESULTS: Twenty patients treated with HDR prostate brachytherapy at our center were included in this retrospective evaluation. For the cohort, mean distance to agreement was 2.1 ± 0.8 mm, 0.60 ± 0.08 mm, 2.0 ± 0.5 mm, and 0.59 ± 0.06 mm for RR, CB, pfRR, and pfCB, respectively. Dice similarity coefficients were 0.80 ± 0.05, 0.93 ± 0.02, 0.81 ± 0.03, and 0.93 ± 0.01 for RR, CB, pfRR, and pfCB, respectively. The inclusion of the Predictive Fusion workflow did not significantly improve the quality of the registration. CONCLUSIONS: The CB deformable registration algorithm in the MIM treatment planning system yielded the best geometric registration indices. MIM offers a commercial platform allowing for easier access and integration into clinical departments with the potential to play an integral role in future focal therapy applications for prostate cancer.

Structure guided deformable image registration for treatment planning CT and post stereotactic body radiation therapy (SBRT) Primovist® (Gd-EOB-DTPA) enhanced MRI.

The purpose of this study was to assess the performance of structure-guided deformable image registration (SG-DIR) relative to rigid registration and DIR using TG-132 recommendations. This assessment was performed for image registration of treatment planning computed tomography (CT) and magnetic resonance imaging (MRI) scans with Primovist® contrast agent acquired post stereotactic body radiation therapy (SBRT). SBRT treatment planning CT scans and posttreatment Primovist® MRI scans were obtained for 14 patients. The liver was delineated on both sets of images and matching anatomical landmarks were chosen by a radiation oncologist. Rigid registration, DIR, and two types of SG-DIR (using liver contours only; and using liver structures along with anatomical landmarks) were performed for each set of scans. TG-132 recommended metrics were estimated which included Dice Similarity Coefficient (DSC), Mean Distance to Agreement (MDA), Target Registration Error (TRE), and Jacobian determinant. Statistical analysis was performed using Wilcoxon Signed Rank test. The median (range) DSC for rigid registration was 0.88 (0.77-0.89), 0.89 (0.81-0.93) for DIR, and 0.90 (0.86-0.94) for both types of SG-DIR tested in this study. The median MDA was 4.8 mm (3.7-6.8 mm) for rigid registration, 3.4 mm (2.4-8.7 mm) for DIR, 3.2 mm (2.0-5.2 mm) for SG-DIR where liver structures were used to guide the registration, and 2.8 mm (2.1-4.2 mm) for the SG-DIR where liver structures and anatomical landmarks were used to guide the registration. The median TRE for rigid registration was 7.2 mm (0.5-23 mm), 6.8 mm (0.7-30.7 mm) for DIR, 6.1 mm (1.1-20.5 mm) for the SG-DIR guided by only the liver structures, and 4.1 mm (0.8-19.7 mm) for SG-DIR guided by liver contours and anatomical landmarks. The SG-DIR shows higher liver conformality as per TG-132 metrics and lowest TRE compared to rigid registration and DIR in Velocity AI software for the purpose of registering treatment planning CT and post-SBRT MRI for the liver region. It was found that TRE decreases when liver contours and corresponding anatomical landmarks guide SG-DIR.

Development and clinical implementation of eclipse scripting-based automated patient-specific collision avoidance software.

PURPOSE: Increased use of Linac-based stereotactic radiosurgery (SRS), which requires highly noncoplanar gantry trajectories, necessitates the development of efficient and accurate methods of collision detection during the treatment planning process. This work outlines the development and clinical implementation of a patient-specific computed tomography (CT) contour-based solution that utilizes Eclipse Scripting to ensure maximum integration with clinical workflow. METHODS: The collision detection application uses triangle mesh structures of the gantry and couch, in addition to the body contour of the patient taken during CT simulation, to virtually simulate patient treatments. Collision detection is performed using Binary Tree Hierarchy detection methods. Algorithm accuracy was first validated for simple cuboidal geometry using a calibration phantom and then extended to an anthropomorphic phantom simulation by comparing the measured minimum distance between structures to the predicted minimum distance for all allowable orientations. The collision space was tested at couch angles every 15° from 90 to 270 with the gantry incremented by 5° through the maximum trajectory. Receiver operating characteristic curve analysis was used to assess algorithm sensitivity and accuracy for predicting collision events. Following extensive validation, the application was implemented clinically for all SRS patients. RESULTS: The application was able to predict minimum distances between structures to within 3 cm. A safety margin of 1.5 cm was sufficient to achieve 100% sensitivity for all test cases. Accuracy obtained was 94.2% with the 5 cm clinical safety margin with 100% true positive collision detection. A total of 88 noncoplanar SRS patients have been currently tested using the application with one collision detected and no undetected collisions occurring. The average time for collision testing per patient was 2 min 58 s. CONCLUSIONS: A collision detection application utilizing patient CT contours was developed and successfully clinically implemented. This application allows collisions to be detected early during the planning process, avoiding patient delays and unnecessary resource utilization if detected during delivery.

Hyperpolarized choline as an MR imaging molecular probe: feasibility of in vivo imaging in a rat model.

PURPOSE: To assess the feasibility of choline MRI using a new choline molecular probe for dynamic nuclear polarization (DNP) hyperpolarized MRI. MATERIALS AND METHODS: Male Sprague-Dawley rats with an average weight of 400 ± 20 g (n = 5), were anesthetized and injection tubing was placed in the tail vein. [1,1,2,2-D4 , 1-(13) C]choline chloride (CMP1) was hyperpolarized by DNP and injected into rats at doses ranging from 12.6 to 50.0 mg/kg. Coronal projection (13) C imaging was performed on a 3 Tesla clinical MRI scanner (bore size 60 cm) using a variable flip angle gradient echo sequence. Images were acquired 15 to 45 s after the start of bolus injection. Signal intensities in regions of interest were determined at each time point and compared. RESULTS: (13) C MRI images of hyperpolarized CMP1 at a 50 mg/kg dose showed time-dependent organ distribution patterns. At 15 s, high intensities were observed in the inferior vena cava, heart, aorta, and kidneys. At 30 s, most of the signal intensity was localized to the kidneys. These distribution patterns were reproduced using 12.6 and 25 mg/kg doses. At 45 s, only signal in the kidneys was detected. CONCLUSION: Hyperpolarized choline imaging with MRI is feasible using a stable-isotope labeled choline analog (CMP1). Nonradioactive imaging of choline accumulation may provide a new investigatory dimension for kidney physiology. J. Magn. Reson. Imaging 2015;41:917-923. © 2014 Wiley Periodicals, Inc.

Anatomical, functional and metabolic imaging of radiation-induced lung injury using hyperpolarized MRI.

MRI of hyperpolarized (129)Xe gas and (13)C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized (129)Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (T(tr)) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-(13)C]pyruvate. In this work, the application of hyperpolarized (129)Xe and (13)C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, T(tr) and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis.

Construction and evaluation of a switch-tuned (13) C - (1) H birdcage radiofrequency coil for imaging the metabolism of hyperpolarized (13) C-enriched compounds.

PURPOSE: To construct a switch-tuned (13) C - (1) H birdcage radiofrequency (RF) coil system capable of metabolic imaging of hyperpolarized (13) C-enriched metabolic probes for co-registration with MRI morphology using protons. MATERIALS AND METHODS: The switch-tuned coil was constructed using PIN diodes for rapid switching of the resonant frequency of the coil. Identical, single-tuned, (1) H and (13) C birdcage RF coils have also been constructed for comparison of imaging performance. A (13) C receive-only surface RF coil has been integrated with the switch-tuned coil for transmit-only, receive-only operation (TORO) to increase local (13) C signal for improved signal-to-noise ratio (SNR). RESULTS: The SNR achieved with the switch-tuned coil in transmit/receive mode was 87% that of the single-tuned (1) H coil. For (13) C imaging, the SNR for the switch-tuned coil was 55% that of the single-tuned (13) C coil. TORO operation of the switch-tuned coil with the surface coil increased SNR for by a factor of 4.2 over transmit/receive operation of the switch-tuned coil alone. CONCLUSION: A surface coil can be integrated with a switch-tuned (13) C - (1) H coil for (13) C TORO operation producing improved SNR. In vivo metabolic imaging of [1-(13) C]pyruvate in a rat model of glioma is demonstrated using TORO operation, which is co-registered with (1) H-imaged anatomy.

Longitudinal anatomical and metabolic MRI characterization of orthotopic xenograft prostate tumors in nude mice.

PURPOSE: To assess anatomic and functional magnetic resonance imaging (MRI) for monitoring of tumor volume and metabolism of orthotopic xenograft prostate cancer tumors. MATERIALS AND METHODS: Human-derived PC-3M cells were implanted into the prostate in 22 nude mice. Tumor volume and MRI appearance were monitored for up to 29 days. Histology was performed to detect metastases. Hyperpolarized [1-(13) C]pyruvate MRI was used to measure tumor metabolism on day 22. RESULTS: Tumors were visible by MRI 9 days after tumor cell implantation. Tumor volume increased to 720 ± 190 mm(3) on day 29 of imaging. Metastasis was seen in the iliac lymph nodes at all timepoints, and in more distant lymph nodes at later timepoints, but was not detectable by MRI. Regions with low pyruvate uptake corresponded to regions with necrosis and had a higher lactate/pyruvate ratio (0.98 ± 0.4 vs. 1.6 ± 1.1). CONCLUSION: MRI using the balanced steady-state free precession (bSSFP) sequence can be used to monitor tumor growth in orthotopic PC-3M tumors as early as 9 days post-injection. Hyperpolarized pyruvate MRI has potential to assess tumor metabolism and necrosis.

Development of an EGSnrc multi-leaf collimator component module and treatment head model for a low-field MRI linear accelerator.

BACKGROUND: Monte Carlo (MC) modeling of MR-guided radiotherapy (MRgRT) treatment machines enables the characterization of photon/electron interactions in the presence of a magnetic field. The EGSnrc MC code system is a well-established system for radiation dose calculations. The multi-leaf collimator (MLC) component modules presently available within the EGSnrc MC code system do not include a model of the double-focused MLC available on a low-field (0.35T) MRI linear accelerator (MR linac). PURPOSE: Here we developed and validated a new component module (CM) for the low-field MRgRT MLC using the EGSnrc/BEAMnrc/DOSXYZnrc code system. We performed detailed modeling of the treatment head and validated the model using measurements and calculations from the vendor-specific treatment planning system (TPS). METHODS: The detailed geometry of the low-field MR linac MLC and other treatment head structures were modeled using BEAMnrc. Comparisons of DOSXYZnrc simulated dose against measurements and the low-field MR linac TPS for a variety of AAPM TG-53 task group report suggested square and shaped fields, as well as a step-and-shoot intensity-modulated radiotherapy (IMRT) plan, are presented. RESULTS: Our model agrees with both measured and TPS calculated data on average within 2%/2 mm (dose/DTA) criterion for square field profiles. Output factors agreed within 1% for field sizes down to 2.49 × 2.49 cm2 and within 2% of TPS data for the smallest field size of 0.83 × 0.83 cm2. Shaped field and IMRT MC calculations agreed with measured and TPS data such that the gamma pass rates (3%/2 mm) were 99.5% and (3%/3 mm) 96.2%, respectively. CONCLUSIONS: We developed and validated an MLC CM (SYNCVRMLC) for the low-field MR linac using the EGSnrc MC code systems. This new CM will facilitate MC computation of fluence and dose distributions using BEAMnrc/DOSXYZnrc for patients treated on the low-field MR linac.

Acute toxicity outcomes from salvage high-dose-rate brachytherapy for locally recurrent prostate cancer after prior radiotherapy.

Purpose: Isolated intra-prostatic recurrence of prostate adenocarcinoma after definitive radiotherapy presents a challenging clinical scenario. Salvage options require specialized expertise and pose risks of harm. This study aimed to present the acute toxicity results from using salvage high-dose-rate brachytherapy (sHDR-BT) as treatment in locally recurrent prostate cancer cases. Material and methods: Seventeen consecutive patients treated with sHDR-BT between 2019 and 2022 were evaluated retrospectively. Eligible patients had to have received curative intent prostate radiotherapy previously, and showed evidence of new biochemical failure. Evaluation with American Urological Association (AUA) and Common Terminology Criteria for Adverse Events (CTCAE) symptom assessments were performed for each case. Results: The median (inter-quartile range) age prior to salvage treatment was 68 (66-74) years. The median post-sHDR-BT follow-up time was 20 (13-24) months. At baseline prior to sHDR-BT, 8 (47%) patients had significant lower urinary tract symptoms. The median AUA score prior to sHDR-BT was 7 (3-18). Three (18%) patients reported irregular bowel function and 2 (12%) reported hematochezia prior to sHDR-BT. One-month post-treatment, the median AUA score was 13 (8-21, p = 0.21). Using CTCAE scoring, there were no cases of grade 2+ bowel or rectal toxicity, and no cases of grade 3+ urinary toxicity. Reported grade 2 urinary toxicities included 10 (59%) cases of bladder spasms, 2 (12%) cases of incontinence, 1 (6%) urinary obstruction, and 4 (24%) reports of urinary urgency. All these adverse events were temporary. Conclusions: This study adds to the existing literature by demonstrating that the acute toxicity profile of sHDR-BT is acceptable even without intra-operative magnetic resonance (MR) guidance or image registration. Further study is ongoing to determine long-term efficacy and toxicity of treatment.

Stereotactic Optimized Automated Radiotherapy (SOAR): a novel automated planning solution for multi-metastatic SRS compared to HyperArc™.

Objective.Automated Stereotactic Radiosurgery (SRS) planning solutions improve clinical efficiency and reduce treatment plan variability. Available commercial solutions employ a template-based strategy that may not be optimal for all SRS patients. This study compares a novel beam angle optimized Volumetric Modulated Arc Therapy (VMAT) planning solution for multi-metastatic SRS to the commercial solution HyperArc.Approach.Stereotactic Optimized Automated Radiotherapy (SOAR) performs automated plan creation by combining collision prediction, beam angle optimization, and dose optimization to produce individualized high-quality SRS plans using Eclipse Scripting. In this retrospective study 50 patients were planned using SOAR and HyperArc. Assessed dose metrics included the Conformity Index (CI), Gradient Index (GI), and doses to organs-at-risk. Complexity metrics evaluated the modulation, gantry speed, and dose rate complexity. Plan dosimetric quality, and complexity were compared using double-sided Wilcoxon signed rank tests (α= 0.05) adjusted for multiple comparisons.Main Results.The median target CI was 0.82 with SOAR and 0.79 with HyperArc (p < .001). Median GI was 1.85 for SOAR and 1.68 for HyperArc (p < .001). The median V12Gy normal brain volume for SOAR and HyperArc were 7.76 cm3and 7.47 cm3respectively. Median doses to the eyes, lens, optic nerves, and optic chiasm were statistically significant favoring SOAR. The SOAR algorithm scored lower for all complexity metrics assessed.Significance.In-house developed automated planning solutions are a viable alternative to commercial solutions. SOAR designs high-quality patient-specific SRS plans with a greater degree of versatility than template-based methods.

Probabilistic Nested Model Selection in Pharmacokinetic Analysis of DCE-MRI Data in Animal Model of Cerebral Tumor.

Purpose: Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace. This study introduces an unsupervised feature engineering technique (Kohonen-Self-Organizing-Map (K-SOM)) to estimate the voxel-wise probability of each nested model. Methods: Sixty-six immune-compromised-RNU rats were implanted with human U-251N cancer cells, and DCE-MRI data were acquired from all the rat brains. The time-trace of change in the longitudinalrelaxivity Δ R 1 for all animals' brain voxels was calculated. DCE-MRI pharmacokinetic (PK) analysis was performed using NMS to estimate three model regions: Model-1: normal vasculature without leakage, Model-2: tumor tissues with leakage without back-flux to the vasculature, Model-3: tumor vessels with leakage and back-flux. Approximately two hundred thirty thousand (229,314) normalized Δ R 1 profiles of animals' brain voxels along with their NMS results were used to build a K-SOM (topology-size: 8×8, with competitive-learning algorithm) and probability map of each model. K-fold nested-cross-validation (NCV, k=10) was used to evaluate the performance of the K-SOM probabilistic-NMS (PNMS) technique against the NMS technique. Results: The K-SOM PNMS's estimation for the leaky tumor regions were strongly similar (Dice-Similarity-Coefficient, DSC=0.774 [CI: 0.731-0.823], and 0.866 [CI: 0.828-0.912] for Models 2 and 3, respectively) to their respective NMS regions. The mean-percent-differences (MPDs, NCV, k=10) for the estimated permeability parameters by the two techniques were: -28%, +18%, and +24%, for v p , K trans , and v e , respectively. The KSOM-PNMS technique produced microvasculature parameters and NMS regions less impacted by the arterial-input-function dispersion effect. Conclusion: This study introduces an unsupervised model-averaging technique (K-SOM) to estimate the contribution of different nested-models in PK analysis and provides a faster estimate of permeability parameters.

Estimated absolute percentage of biopsied tissue positive for Gleason pattern 4 (eAPP4) in low dose rate prostate brachytherapy: Evaluation of prognostic utility in a large cohort.

PURPOSE: To determine whether a system to estimate Absolute Percentage of Biopsied Tissue Positive for Gleason Pattern 4 (eAPP4) is useful as a prognostication tool for patients with intermediate risk prostate cancer (IR-PCa) undergoing low dose rate prostate brachytherapy. METHODS: 497 patients with IR-PCa and known grade group 2 or 3 disease treated with low dose rate seed brachytherapy (LDR-BT) at a quaternary cancer centre were retrospectively reviewed. Prostate biopsies for each patient included Gleason grading with synoptic reporting that did not include percentage of pattern 4 disease found within the sample. Each core was assigned a grade grouping, however, and that was used with optimized estimates of percentage of pattern four disease to estimate eAPP4. Outcomes including cumulative incidence of recurrence (CIR), treatment of recurrent disease (RRX), and metastasis-free survival (MFS) were then reviewed and the prognostic value of eAPP4 evaluated. RESULTS: 428 (86%) patients had Gleason grade group 2 and 69 (14%) patients had Gleason grade group 3 disease. 230 (46%) patients had National Comprehensive Cancer Network (NCCN) favourable intermediate at baseline, while 267 (54%) of patients had NCCN unfavourable intermediate at baseline. Median follow-up was 7.3 (5.5-9.6) years. eAPP4 was predictive of CIR (p = 0.003), RRX (p = 0.003), or MFS (p = 0.001) events, while Gleason grade grouping alone was not. eAPP4 was strongest as a predictor for MFS when estimates of 30% (grade group 2) and 80% (grade group 3) were used [HR 1.07 (1.03-1.12); p = 0.001]. CONCLUSIONS: eAPP4 was strongly predictive of recurrence and metastasis-free survival in a large cohort of patients receiving LDR-BT treatment for IR-PCa. Treatment of future patients with IR-PCa could include the use of eAPP4 prognostication.

Fast stereotactic radiosurgery planning using patient-specific beam angle optimization and automation.

BACKGROUND AND PURPOSE: Linac-based stereotactic radiosurgery (SRS) planning for multi-metastatic cases is a complex and intensive process. A manual planning strategy starts with a template-based set of beam angles and applies modifications though a trial and error process. Beam angle optimization uses patient specific geometric heuristics to determine beam angles that provide optimal target coverage and avoid treating through Organs-at-Risk (OARs). This study expands on a collision prediction application developed using an application programming interface, integrating beam angle optimization and collision prediction into a Stereotactic Optimized Automated Radiotherapy (SOAR) planning algorithm. MATERIALS AND METHODS: Twenty-five patient plans, previously treated with SRS for multi-metastatic intracranial tumors, were selected for a retrospective plan study comparing the manual planning strategy to SOAR. The SOAR algorithm was used to select isocenters, table, collimator, and gantry angles, and target groupings for the optimized plans. Dose-volume metrics for relevant OARs and PTVs were compared using double-sided Wilcoxon signed rank tests (α = 0.05). A subset of five patients were included in an efficiency study comparing manual planning times to SOAR automated times. RESULTS: OAR dose metrics compared between planning strategies showed no statistical difference for the dataset of twenty-five plans. Differences in maximum PTV dose and the conformity index were improved for SOAR planning and statistically significant. The median SOAR planning time was 9.8 min compared to 55 min for the manual planning strategy. CONCLUSIONS: SOAR planning was comparable in plan quality to a manual planning strategy with the possibility for greatly improving planning efficiency through automation.

Auto-delineation framework for the focal liver reaction observed in post Stereotactic Body Radiation Therapy (SBRT) Primovist MRI scans.

Development of a novel auto-delineation methodology for observed hypointensity from focal liver reaction in hepatobiliary-specific contrast (Primovist) enhanced MRI acquired post Stereotactic Body Radiation Therapy (SBRT). Additionally, the methodology for the quantification of the threshold dose associated with the observed focal liver reaction was also established. An auto-delineation algorithm was created based on the correlation between intensity and radiation dose information. The error associated with the auto-delineation was quantified using virtual FLRs, as well as clinical patient scans. Patients underwent liver SBRT with a total dose prescription of 50 Gy in 5 fractions. An inherent correlation was established between the contrast-to-noise ratio (CNR) on MRI scans and expected performance of the algorithm using centre-of-mass (COM). Threshold dose associated with focal liver reaction was quantified for all ten patients and verified with associated most conformal isodose line. Based on the CNR vs COM error relationship, the expected median (range) auto-delineation COM error for ten patients was 0.5 (0 to 3.2) mm. The median threshold dose for ten clinical cases was 21.3 Gy based on the auto-delineation framework. This threshold dose was compared to the most conformal isodose line with the hypointensity; there was no significant difference observed (p = 0.6). We developed a framework for post-SBRT Primovist observed focal liver reaction localization. Furthermore, this study established an automated approach for the determination of the threshold dose associated with the hypointense region.

Competency-Based Medical Education in Radiation Therapy Treatment Planning.

PURPOSE: To develop a technology-enhanced education methodology with competency-based evaluation for radiation therapy treatment planning. The education program is designed for integration in the existing framework of Commission on Accreditation of Medical Physics Education Programs (CAMPEP) accredited medical physics residency programs. METHODS AND MATERIALS: This education program pairs an accessible, multi-institutional infrastructure with established medical education evaluation tools to modernize treatment planning education. This program includes 3 evaluation components: (1) competency-based evaluation, (2) inter- and intramodality comparison, and (3) learner feedback. For this study, synchronous bilateral breast cancer was selected to demonstrate a complex treatment site and nonstandardized technique. Additionally, an online study was made available to a public cohort of worldwide participants of certified Medical Dosimetrists and Medical Physicists to benchmark performance. Before evaluation, learners were given a disease site-specific education session on potential clinical treatment strategies. During the assessment, learners generated treatment plans in their institutional planning system under the direct observation of an expert evaluator. Qualitative proficiency was evaluated for all learners on a 5-point scale of graduated task independence. Quantitative dosimetry was compared between the learner cohort and public cohort. A feedback session provided learners context of multi-institutional experience through multimodality and technique comparison. After study completion, learners were provided a survey that was used to gauge their perception of the education program. RESULTS: In the public study, 34 participants submitted treatment plans. Across 3 CAMPEP-accredited residency programs, 6 learners participated in the education and evaluation program. All learners successfully completed treatment plans that met the dosimetric constraints described in the case study. All learners favorably reviewed the study either comprehensively or in specified domains. CONCLUSIONS: The competency-based education and evaluation program developed in this work has been incorporated in CAMPEP-accredited residency programs and is adaptable to other residency programs with minimal resource commitment.

Increasing Demand on Human Capital and Resource Utilization in Radiation Therapy: The Past Decade.

PURPOSE: To quantify the change resource utilization in radiation therapy in the context of advancing technologies and techniques over the last decade. METHODS AND MATERIALS: Prospectively, the time to complete radiation therapy workflow tasks was captured between January 1, 2020, and December 31, 2020. The institutional task workflows are specific to each technique and broadly organized into 4 categories: 3-dimenstional conformal radiation therapy, intensity modulated radiation therapy, volumetric modulated arc therapy simple, and volumetric modulated arc therapy complex. These discipline-specific task times were used to quantify a resource utilization factor, which is the median time taken to complete all tasks for each category divided by the median time for 3-dimensional conformal radiation therapy treatments. Retrospectively, all plans treated between January 1, 2012, and December 31, 2019, were quantified and categorized. The resource factor was applied to determine resource utilization. For context, institutional staffing levels were captured across the same decade for medical dosimetrists, medical physicists, and radiation oncologists. RESULTS: This analysis includes 30,229 patient plans in the retrospective data set and 4747 patient plans in the prospective data set. This analysis demonstrates that over this period, patient numbers increased by approximately 45%, whereas time-based human resources increased by almost 150%. The resource allocation factors for 3-dimenstional conformal radiation therapy, intensity modulated radiation therapy, volumetric modulated arc therapy simple, and volumetric arc therapy complex were 1.0, 2.4, 2.9, and 4.3, respectively. Across the 3 disciplines, staffing levels increased from 15 to 17 (13%) for medical dosimetrists, from 10 to 13 (30%) for medical physicists, and from 16 to 23 (44%) for radiation oncologists. CONCLUSIONS: This work demonstrates the increase in resource utilization due to the introduction of advanced technologies and changes in radiation therapy techniques over the past decade. Human resource utilization is the predominant factor and should be considered with increasing patient volume for operational planning.

Technical Note: A standardized automation framework for monitoring institutional radiotherapy protocol compliance.

PURPOSE: To establish a framework for the standardization of monitoring radiotherapy protocol compliance. METHODS: An automated protocol compliance tool was developed using best practice in software design and a flexible framework to easily adapt to changing institutional standards. The Eclipse scripting environment was used to develop the application with the scripting application programing interface (API) and direct data extraction from ARIA. For each institutional protocol, external validation was specified in a JavaScript Object Notation (JSON) file that stores protocol specific constraints and evaluates compliance of the data from Eclipse and Aria. This tool was applied prospectively to a cohort of prostate cancer patients undergoing radiotherapy with a prescription regimen of 60 Gy in 20 fractions. RESULTS: The prospective evaluation was performed on 58 prostate cancer patients. For this cohort, the mean (standard deviation) pass rate is 92.3% (6.1%). The overall fail rate is 6.0% (5.8%); the percentage of these failures is in 2.6% in Patient Assessment, 0% in Simulation, and 97.4% in Treatment Planning. CONCLUSIONS: A protocol compliance application is developed and implemented in a standard radiotherapy information system. The application functionality is demonstrated on a cohort of 58 patients undergoing prostate radiotherapy, which highlights the utility of assessing adherence to institutional protocols. A unified method must be available for the community to ensure consistency in compliance reporting.

Excessive waitlists and delays to treatment with low-dose-rate brachytherapy predict an increased risk of recurrence and metastases in intermediate-risk prostatic carcinoma.

PURPOSE: It has previously been shown that increased wait times for prostatectomy are associated with poorer outcomes in intermediate-risk prostatic carcinoma (PCa). However, the impact of wait times on PCa outcomes following low-dose-rate brachytherapy (LDR-BT) are unknown. METHODS AND MATERIALS: We retrospectively reviewed 466 intermediate-risk PCa patients that underwent LDR-BT at a single comprehensive cancer center between 2003 and 2016. Wait times were defined as the time from biopsy to LDR-BT. The association of wait times with outcomes was evaluated using Cox and Fine-Gray regression in both univariate and multivariate models. RESULTS: Median (interquartile range) follow-up and wait time for all patients were 8.1 (6.3-10.4) years and 5.1 (3.9-6.9) months, respectively. Among NCCN unfavourable intermediate-risk (UIR) patients (n = 170; 36%), increased wait times predicted both a greater cumulative incidence of recurrence [MHR = 1.01/month of wait time (95% CI: 1.00-1.03); P = 0.044] and metastases [MHR = 1.04/month of wait time (95% CI: 1.02-1.06); P < 0.001] in multivariate modeling. In NCCN favourable intermediate-risk (FIR) patients, there was no significant association between wait time and recurrence or metastases risk. Among all intermediate-risk patients, wait time was associated with an increase in the incidence of metastases [MHR = 1.03/month of wait time (95% CI: 1.02-1.05); P < 0.001], but not recurrence in multivariate models. There was no association between wait time and overall survival in the UIR, FIR, or all intermediate-risk cohorts. CONCLUSIONS: Resource constraints within this center's public healthcare system have contributed to waitlists exceeding 5-months in length. This study finds that patients with UIR PCa experience a 1% increase in the risk of recurrence and 4% increase in the risk of metastases with each additional month of delay in definitive disease management. Preventing such extended management delays in LDR-BT may improve disease-related outcomes in patients with PCa.

Clinical Outcomes from Dose-Reduced Radiotherapy to the Prostate in Elderly Patients with Localized Prostate Cancer.

Radical treatment of localized prostate cancer in elderly patients may lead to unacceptable treatment-associated toxicities that adversely impact quality of life without improving survival outcomes. This study reports on a cohort of 54 elderly (>70 years) patients that received 4000-5000 cGy of palliative external beam radiotherapy (EBRT) as an alternative to androgen deprivation therapy (ADT). The primary outcome of interest was the period of ADT-free survival, and secondary outcomes included overall survival (OS) and metastases-free survival (MFS). Kaplan-Meier regression was used to estimate survival outcomes. Thirty-six (67%) patients achieved a break in ADT post-radiotherapy, with a median time to ADT reinitiation of 20 months. Common Terminology Criteria for Adverse Events (CTCAE) were limited to low-grade gastrointestinal (GI) or genitourinary (GU) toxicities, with no skin toxicities observed. Grade 1 GI toxicity was observed in 9 (17%) patients, and grades 1 and 2 GU toxicities were observed in 13 (24%) and 3 (6%) patients, respectively, with no higher-grade toxicities reported. Five-year MFS and OS were 56% and 78%, respectively. In summary, the treatment regimen was well-tolerated and achieved durable ADT-free survival in most patients. Dose-reduced EBRT appears to be a viable alternative to ADT in elderly patients with localized prostate cancer.