Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study.

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown. In this proof-of-concept study, we showed, for the first time, the neuroepigenetic biomarker capability of non-invasive imaging of class I histone deacetylase (HDAC) epigenetic enzymes in the in vivo brain for classifying AUD patients from healthy controls using a machine learning approach in the context of precision diagnosis. Eleven AUD patients and 16 age- and sex-matched healthy controls completed a simultaneous positron emission tomography-magnetic resonance (PET/MR) scan with the HDAC-binding radiotracer [11C]Martinostat. Our results showed lower HDAC expression in the anterior cingulate region in AUD. Furthermore, by applying a genetic algorithm feature selection, we identified five particular brain regions whose combined [11C]Martinostat relative standard uptake value (SUVR) features could reliably classify AUD vs. controls. We validate their promising classification reliability using a support vector machine classifier. These findings inform the potential of in vivo HDAC imaging biomarkers coupled with machine learning tools in the objective diagnosis and molecular translation of AUD that could complement the current diagnostic and statistical manual of mental disorders (DSM)-based intervention to propel precision medicine forward.

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.

Assessment of dose to vaginal mucosa for gynecologic template interstitial high-dose-rate brachytherapy using Monte Carlo simulation.

Purpose: This study investigated reliable vaginal mucosa dose-volume histogram (DVH) metrics in gynecologic template interstitial high-dose-rate brachytherapy (HDR-BT) for the purpose of standardized dose reporting. Material and methods: Gynecologic template (Syed/Neblett) interstitial HDR-BT patients treated from September 2016 to November 2022 at the study institute were included in the cohort. Each patient implant included a vaginal mucosa contour defined by a 5 mm expansion from vaginal cylinder, then another volume with clinical target volume subtracted. DVH metrics were investigated between D0.1cc to D4cc. Clinical plans were re-calculated using Monte Carlo (MC) simulations both in heterogeneous material and in water. Results: The patient cohort included 61 patients with clinical plans using conventional homogeneous dose calculation (TG43). Heterogeneous vs. water MC dose differences were between -1.1% and -1.4% for all metrics investigated. DVH metrics D1cc and smaller resulted in > 5% discrepancies between TG43 and MC dose (to water) calculation due to the proximity of source positions in/nearby the vaginal mucosa. Reliability improved when DVH metric volume was larger (D2cc and D4cc). Both D2cc and D4cc presented very high linear correlation between TG43 and MC reported doses for the vagina, and average ± standard deviation dose difference was 4.6 ±2.9% and -3.0 ±1.9%, respectively. Dose differences decreased when the clinical target volume was removed: -1.5 ±3.5% and -0.8 ±2.1% for D2cc and D4cc, respectively. Conclusions: For perineal template gynecologic HDR-BT procedures, the 2 cc volume is the smallest representative volume that reliably reports vaginal dose and at minimum should be reported to establish dose and outcome evaluation.

Clinical implementation of 3D transvaginal ultrasound for intraoperative guidance of needle implant in template interstitial gynecologic high-dose-rate brachytherapy.

PURPOSE: To demonstrate novel clinical implementation of a 3D transvaginal ultrasound (3DTVUS) system for intraoperative needle insertion guidance in perineal template interstitial gynecologic high-dose-rate brachytherapy and assess its impact on implant quality. METHODS AND MATERIALS: Interstitial implants began with preimplant 3DTVUS to visualize the tumor and anatomy, with intermittent 3DTVUS to assess the implant and guide needle adjustment. Analysis includes visualization of the implant relative to anatomy, identification of cases where 3DTVUS is beneficial, dosimetry, and a survey distributed to 3DTVUS clinicians. RESULTS: Seven patients treated between November 2021 and October 2022 were included in this study. Twenty needles were inserted under 3DTVUS guidance. The tumor and vaginal wall were well-differentiated in four and all seven patients, respectively. Patients with tumours below the superior aspect of the vagina are suited for 3DTVUS. Four radiation oncologists responded to the survey. There was general agreement that 3DTVUS improves implant and anatomy visualization and is preferred over standard 2D ultrasound guidance techniques. CONCLUSIONS: Based on qualitative feedback from primary users and a small preliminary patient cohort, 3DTVUS imaging improves tumor and vaginal wall visualization during gynecologic perineal template interstitial needle implant and is a powerful tool for implant assessment in an intraoperative setting.

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.

An updated approach for deriving PTV margins using image guidance and deformable dose accumulation.

Objective.To demonstrate an updated approach for deriving planning target volume (PTV) margins for a patient population treated with volumetric image-guided radiotherapy.Approach.The approach uses a semi-automated workflow within commercial radiotherapy applications that combines dose accumulation with the bidirectional local distance (BLD) metric. The patient cohort is divided into derivation and validation datasets. For each patient in the derivation dataset, a treatment plan is generated with a 0 mm PTV margin (the idealized treatment scenario without the influence of the standard margin). Deformable image registration enabled dose accumulation of these zero-margin plans. PTV margins are derived by using the BLD to calculate the geometric extent of underdosed regions of the clinical target volume (CTV). The PTV margin is validated by ensuring the specified CTV coverage criterion is met when the margin is applied to the validation dataset.Main results.The methodology was applied to two cohorts: 40 oropharyngeal cancer patients and 50 early-stage breast cancer patients. Ten patients from each cohort were used for validation. PTV margins derived for the oropharyngeal and early-stage breast cancer patient cohorts were 3 and 5 mm, respectively, and ensure that 95% of the prescription dose is delivered to 98% of the CTV for 90% of patients. Dose accumulation showed that the CTV coverage criterion was achieved for at least 90% of patients when the margins were applied.Significance.This methodology can be used to derive appropriate PTV margins for realistic treatment scenarios and any disease site, which will improve our understanding of patient outcomes.

Technical note: Commissioning of an ultrasound-compatible surrogate vaginal cylinder for transvaginal ultrasound-based gynecologic high-dose-rate brachytherapy.

PURPOSE: To provide a comprehensive set of commissioning tests for clinical implementation of three-dimensional transvaginal ultrasound (3D TVUS) as a replacement of computed tomography (CT) for applicator reconstruction in gynecologic (GYN) intracavitary high-dose-rate brachytherapy (HDRBT) with a multi-channel vaginal cylinder (MCVC). METHODS: We introduce an ultrasound-compatible "surrogate" vaginal cylinder (SVC) for reconstruction of Elekta's CT-MR Multi Channel Applicator (MCVC) in 3D TVUS. The MCVC is digitized over the SVC in 3DUS using digital library model overlay. Consulting guidelines from various sources (CPQR, GEC-ESTRO, AAPM), we identify and describe three tests specific to commissioning the SVC: (1) verification of SVC outer dimensions, (2) source position accuracy of MCVC digitization over the SVC in 3D TVUS, and (3) MRI/US registration error. RESULTS: The SVC outer dimensions (diameter and A-D marker locations) were well matched to the MCVC, however a 0.6 mm discrepancy in length between cylinder tips was observed. Source position accuracy was within 1 mm (tolerance recommended by CPQR) when reconstructing the MCVC in 3D TVUS. Dice similarity coefficients and target registration error for MRI/3D TVUS registration was similar to MRI/CT registration, which is the clinical standard. CONCLUSIONS: These commissioning tests are performed using institutional equipment but provide the framework for any practitioner to repeat in their own setup, to demonstrate safe adoption of the 3D TVUS system for patient treatments. We demonstrate that MRI/US-based workflow achieves similar source position accuracy and image registration error as standard MRI/CT, which is consistent with standard tolerances. This is a critical step toward replacement of CT with US in GYN HDRBT treatments with the MCVC.

Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography.

We report the development of the first positron emission tomography (PET) radiotracer, [18F]CNY-07, based on a highly specific and potent RIPK1 inhibitor, Nec-1s, for RIPK1/necroptosis brain imaging in rodents. [18F]CNY-07 was synthesized through copper-mediated 18F-radiolabeling from an aryl boronic ester precursor and studied in vivo PET imaging in rodents. PET imaging results showed that [18F]CNY-07 can penetrate the blood-brain barrier with a maximum percent injected dose per unit volume of 3 at 10 min postinjection in the brain in vivo. Self-blocking studies of [18F]CNY-07 by pretreating with unlabeled molecules in rodents showed reduced radioactivity in animal brains (30% radioactivity decreased), indicating the binding specificity of our radiotracer. Our studies demonstrate that [18F]CNY-07 has provided a useful PET radioligand enabling brain RIPK1 imaging, which could be a valuable research tool in studying RIPK1-related neurological disorders in animals and potentially humans.

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.

Robotic Ultrasound Scanning With Real-Time Image-Based Force Adjustment: Quick Response for Enabling Physical Distancing During the COVID-19 Pandemic.

During an ultrasound (US) scan, the sonographer is in close contact with the patient, which puts them at risk of COVID-19 transmission. In this paper, we propose a robot-assisted system that automatically scans tissue, increasing sonographer/patient distance and decreasing contact duration between them. This method is developed as a quick response to the COVID-19 pandemic. It considers the preferences of the sonographers in terms of how US scanning is done and can be trained quickly for different applications. Our proposed system automatically scans the tissue using a dexterous robot arm that holds US probe. The system assesses the quality of the acquired US images in real-time. This US image feedback will be used to automatically adjust the US probe contact force based on the quality of the image frame. The quality assessment algorithm is based on three US image features: correlation, compression and noise characteristics. These US image features are input to the SVM classifier, and the robot arm will adjust the US scanning force based on the SVM output. The proposed system enables the sonographer to maintain a distance from the patient because the sonographer does not have to be holding the probe and pressing against the patient's body for any prolonged time. The SVM was trained using bovine and porcine biological tissue, the system was then tested experimentally on plastisol phantom tissue. The result of the experiments shows us that our proposed quality assessment algorithm successfully maintains US image quality and is fast enough for use in a robotic control loop.

Intraoperative optimization of seed implantation plan in breast brachytherapy.

PURPOSE: Low-dose-rate permanent-seed (LDR-PS) brachytherapy has shown a great potential for treating breast cancer. An implantation scheme indicating the template pose and needle trajectories is determined before the operation. However, when performing the pre-planned scheme intraoperatively, a change of the patient's posture will cause seed placements away from the desired locations. Hence, the implantation scheme should update based on the current patient's posture. METHODS: A numerical method of optimizing the implantation scheme for the LDR-PS breast brachytherapy is presented here. The proposed algorithm determines the fewest needle trajectories and template poses for delivering the seeds to the intraoperative desired locations. The clinical demand, such as the minimum distance between the chest wall and the needle, is considered in the optimization process. RESULTS: The method was simulated for a given LDR-PS brachytherapy procedure to evaluate the optimal scheme as the number of the template poses changing. The optimization parameters of the needles' number and the implantation errors are used to adjust the algorithm outcome. The results show that the implantation schemes obtained by our method have a satisfactory accuracy in the cases of 2 or 3 template poses. The computation time is about 76s to 150s according to the number of the template poses from 1 to 3. CONCLUSION: The proposed method can find the optimal implantation scheme corresponding to the current desired seed locations immediately once there is a change of patient's posture. This work can be applied to the robot-assisted LDR-PS breast brachytherapy for improving the operation accuracy and efficiency.

Dosimetric consequences of seed placement accuracy in permanent breast seed implant brachytherapy.

PURPOSE: This study quantifies the dosimetric impact of implant accuracy and derives a quantitative relationship relating implant accuracy to target dosimetry. METHODS AND MATERIALS: A framework was developed to simulate multiple implants for error combinations. Spherical clinical target volumes (CTVs) were modeled with volumes 1.4 cm3, 9.2 cm3, and 20.6 cm3, representing the range seen clinically. Each CTV was expanded 10 mm isotropically to create a planning target volume (PTV).. Random and systematic seed placement errors were simulated by shifting needles from their planned positions. Implant errors were simulated over the range of clinically practical errors in permanent breast seed implant. The relative effect on target coverage was evaluated. Regression analysis was performed to derive relationships between CTV dosimetry and the magnitude of implant accuracy. The validity of the clinically used 10 mm PTV margin for each of the CTVs was assessed. RESULTS: Introducing practical implant errors resulted in CTV V90% median (10th and 90th percentile) of 97.7% (85.9% and 100%), 96.2% (86.8% and 99.7%), and 100% (77.8% and 100%) for the typical, large, and small CTV, respectively. All CTVs show similar trends in target coverage. Polynomials were derived relating seed placement accuracy to median (R2 = 0.82) and 10th percentile (R2 = 0.78) CTV V90%.. CONCLUSIONS: This work quantitatively describes the relationship between implant accuracy and CTV coverage. Based on simulations, the 10 mm PTV margin is adequate to maintain target coverage. These equations can be used with institutional seed placement accuracy to estimate coverage.

Dosimetry of a sonolucent material for an ultrasound-compatible gynecologic high-dose-rate brachytherapy cylinder using Monte Carlo simulation and radiochromic film.

PURPOSE: he purpose of this study was to study the dosimetric characterization of sonolucent material "TPX" to be used toward gynecologic high-dose-rate brachytherapy treatments using ultrasound-compatible cylinders in non-model-based dose calculation workflows. METHODS: Monte Carlo simulations were performed using EGSnrc application egs_brachy in cylinders of polymethylpentene (TPX) plastic, water, and PMMA. Simulations were performed of five 192Ir sources placed longitudinally in ∼3.7 cm diameter, 5.0 cm length cylinders (matching physical cylinders used in film measurements). TPX and PMMA dose distributions and percentage depth dose curves were compared relative to water. Film measurements were performed to validate egs_brachy simulations. TPX and PMMA cylinders were placed in a water tank using 3D-printed supports to position film radially and touching the surface of the cylinders. The same five 192Ir dwell positions were delivered as simulated in egs_brachy. RESULTS: The egs_brachy and film percentage depth doses agreed within film uncertainties. The egs_brachy relative dose difference between TPX and water was (0.74 ± 0.09)% and between PMMA and water was (-0.79 ± 0.09)% over the dose scoring phantom. Dose differences for TPX and PMMA relative to water were less than ± 1% within 5 cm of the cylinder surface. CONCLUSIONS: In a solid sonolucent sheath of TPX, the dosimetric differences are comparable with PMMA and other applicator materials in clinical use. No additional uncertainty to dose calculation is introduced when treating through TPX cylinders compared with current applicator materials, and therefore, it is acceptable to perform gynecologic brachytherapy treatments with a sonolucent sheath inserted during radiation delivery.

Implementation of high-dose-rate brachytherapy for prostatic carcinoma in an unshielded operating room facility.

PURPOSE: The purpose of the study was to describe our approach towards safe delivery of single-fraction high-dose-rate (HDR) brachytherapy (BT) boost in patients with prostate cancer in the setting of an unshielded operating room (OR). METHODS AND MATERIALS: A total of 95 patients received 15 Gy HDR BT boost. The procedure involved transrectal ultrasound-based catheter insertion and planning in the OR, after which the patient was moved to a shielded treatment room for radiation. This required three vital components: (1) an OR table capable of transporting the patient in lithotomy position, (2) robust motion management checks to ensure reproducibility of prostate and catheter positions in the treatment room before radiation delivery, (3) remote monitoring of patient vitals while under anesthesia, during the radiation. Initial viability of this approach was confirmed by assessing acute toxicities using the Common Terminology Criteria for Adverse Events v4.0 and American Urologic Association symptom scores. RESULTS: We found good stability in prostate and catheter position, with less than 1 mm shifts in each direction due to patient transfer. The median baseline American Urologic Association score was 7 (3-11), which increased to 12 (7-17) at 4 weeks and 9 (5-14) at 3 months (p = 0.003). Common Terminology Criteria for Adverse Events ≥ grade 2 genitourinary and gastrointestinal toxicities were experienced by 7% and 0% patients, respectively, at 3 months posttreatment completion. CONCLUSIONS: Single-fraction HDR prostate BT can be delivered safely in an unshielded OR facility with a distant shielded treatment room using rigorous motion management checks and supplementary procedural equipment.

Analysis of outcomes after non-contour-based dose painting of dominant intra-epithelial lesion in intra-operative low-dose rate brachytherapy.

PURPOSE: To compare the outcomes of patients with intermediate risk prostate cancer (IR-PCa) treated with low-dose rate I-125 seed brachytherapy (LDR-BT) and targeted dose painting of a histologic dominant intra-epithelial lesion (DIL) to those without a DIL. METHODS: 455 patients with IR-PCa were treated at a single center with intra-operatively planned LDR-BT, each following the same in-house dose constraints. Patients with a DIL on pathology had hot spots localized to that region but no specific contouring during the procedure. RESULTS: 396 (87%) patients had a DIL. Baseline tumor characteristics and overall prostate dosimetry were similar between patients with and without DIL except the median number of biopsy cores taken: 10 (10-12) vs 12 (10-12) (p = 0.002).19 (5%) and 18 (5%) of patients with and 1 (2%) and 0 (0%) of those without DIL experienced CTCAE grade 2 and 3 toxicity respectively. Overall, toxicity grade did not significantly correlate with presence of DIL (p = 0.10).Estimated 7-year freedom from biochemical failure (FFBF) was 84% (95% confidence interval: 79-89) and 70% (54-89) in patients with and without a DIL (log-rank p = 0.315). In DIL patients, cox regression revealed location of DIL ("Base" vs "Apex" HR: 1.03; 1.00-1.06; p = 0.03) and older age (70 vs 60 HR: 1.62; 1.06-2.49; p = 0.03) was associated with poor FFBF. CONCLUSIONS: Targeting DIL through dose painting during intraoperatively planned LDR-BT provided no statistically significant change in FFBF. Patients with DILs in the prostate base had slightly lower FFBF despite DIL boost.

Peer-based credentialing for brachytherapy: Application in permanent seed implant.

PURPOSE: The purpose of the study was to establish a quantitative method for implant quality evaluation in permanent seed implant brachytherapy for credentialing. Delivery-based credentialing will promote consistency in brachytherapy seed delivery and improve patient outcomes. METHODS: A workflow for delivery-based credentialing was outlined and applied to permanent breast seed implant brachytherapy. Delivery simulations were performed on implantable anthropomorphic breast phantoms. Two institutions experienced in permanent seed implant brachytherapy demonstrated the peer credentialing process. Each delivery was evaluated for seed placement accuracy as the measure of implant quality, both for implant accuracy and across five simulations to assess implant variation. Initial credentialing criteria are set based on two factors; the mean seed placement accuracy (implant accuracy) and the mean standard deviation (seed variation) with the threshold for each set with the addition of two standard deviations. RESULTS: Across two institutions, seed placement accuracy (±standard deviation) was calculated for all five delivery simulations to yield 6.1 (±2.6) mm. To set credentialing criteria, the implant accuracy (6.1 mm) plus two standard deviations (2.0 mm) and the seed variation (2.6 mm) plus two standard deviations (0.8) mm yield a threshold of 8.1 ± 3.4 mm. It is expected that 95% of experienced institutions would perform the phantom simulation within this threshold. CONCLUSION: Brachytherapy programs should validate delivery accuracy by formal credentialing, which is standard in external beam programs. This quantitative implant evaluation should be combined with current credentialing standards for permanent seed brachytherapy to form a comprehensive validation of institutional brachytherapy program quality.

Establishing a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy: Building validation evidence.

PURPOSE: The purpose of this study was to establish a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy. The first step in formalizing any education program is a validation process that builds evidence-based verification that the learning environment is appropriate. METHODS AND MATERIALS: The primary education task allowed practitioners to use an anthropomorphic breast phantom to simulate a permanent seed implant brachytherapy delivery. Validation evidence is built by generating data to assess learner and expert cohorts according to their proficiency. Each practitioner's performance during the simulation was evaluated by seed placement accuracy, procedural time-to-complete, and two qualitative evaluation tools-a global rating scale and procedural checklist. RESULTS: The average seed placement accuracy (±SD) was 8.1 ± 3.5 mm compared to 6.1 ± 2.6 mm for the learner and expert cohort, respectively. The median (range) procedural time-to-complete was 64 (60-77) minutes and 43 (41-50) minutes for the learner and expert cohort, respectively. Seed placement accuracy (student t-test, p < 0.05) and procedural time-to-complete (Mann-Whitney U-test, p < 0.05) were statistically different between the cohorts. In both the global rating scale and procedural checklist, the expert cohort demonstrated improved proficiency compared to the learner cohort. CONCLUSIONS: This validation evidence supports the utilization of this simulation environment toward appropriately capturing the delivery experience of practitioners. The results demonstrate that, in all areas of evaluation, expert cohort proficiency was superior to learner cohort proficiency. This methodology will be used to establish a simulation-based education program for radiation oncology learners in permanent seed implant brachytherapy.

A Framework for Clinical Validation of Automatic Contour Propagation: Standardizing Geometric and Dosimetric Evaluation.

PURPOSE: The objective of this work was to outline and demonstrate a standardized framework for evaluating automatically propagated contour quality against expert contours. A 2-pronged approach is used to evaluate contour quality: a geometric evaluation to identify geometric and spatial discrepancies between propagated and expert contours, and a comprehensive dosimetric comparison to provide clinical context for the results. METHODS AND MATERIALS: The standardized framework requires a primary image, with reference contours and a radiation therapy treatment plan, and a secondary image. Reference contours are automatically propagated onto the secondary image anatomy and compared with expert contours obtained in an interobserver study. The standardized framework outlines geometric and dosimetric evaluation methodologies for determining indistinguishability between propagated and expert contours in a cohort analysis. Propagated contours are geometrically compared with expert contours in terms of the Dice similarity coefficient and the mean distance to agreement. Statistical analysis is performed on the central tendency and variability of Dice similarity coefficient and mean distance to agreement values over the patient cohort. Dosimetric evaluation involves computing the mean and 95% confidence intervals for the differences in cumulative dose-volume histograms for propagated and expert contours. A case study in accelerated partial breast irradiation was shown to demonstrate the framework. RESULTS: The standardized framework was applied to a case study of 24 patient data sets with 3 radiation oncologists providing the expert contours. Cohort analysis indicated that propagated contours were geometrically indistinguishable and dosimetrically distinguishable from expert contours. CONCLUSIONS: The recommended framework standardizes the comparison of geometric and dosimetric parameters to demonstrate indistinguishability of propagated contours from expert contours. Adoption of this framework is vital for consistent and comprehensive validation of automatic contour propagation for use in large-scale cohort analyses.

The impact of inter-fraction changes for perineal template-based interstitial gynecologic brachytherapy implants.

PURPOSE: Perineal template-based interstitial gynecologic brachytherapy (ISBT) treatments are evaluated to determine whether adaptive inter-fraction re-planning is beneficial and necessary to meet the treatment aims of the American Brachytherapy Society (ABS) consensus guidelines for interstitial brachytherapy. Adherence to the EMBRACE II protocol is also assessed. MATERIAL AND METHODS: Ten patients receiving radical intent treatment for locally advanced or recurrent gynecologic malignancies underwent a three-fraction ISBT treatment with an ABS-recommended prescription regimen of 21 to 24 Gy. Clinical treatment plans were created according to a computed tomography (CT) acquired immediately post-implant. The first fraction was delivered on the same day as the implant (Day 1). The remaining two fractions were delivered on the next day (Day 2), at least six hours apart. Prior to treating on Day 2, a verification CT was acquired, permitting assessment of over-night changes. The Day 2 CT was used to evaluate deviations in 2-Gy-per-fraction equivalent dose (EQD2) from the clinically intended dosimetry for clinical target volume (CTV), bladder, rectum, and sigmoid. RESULTS: For all patients, the median (range) difference between the intended and the delivered dosimetry for the CTV D90% was 1.4 Gy10 (0.3-4.4 Gy10). For all normal tissues, the median (range) difference from the intended normal tissue dose was 2.6 Gy3 (0.1-15.5 Gy3). In all cases, the deviation from clinically intended dosimetry did not lead to a violation of recommended normal tissue dose guidelines. For two of 10 patients with large normal tissue differences (> 10 Gy3 from the intended dose), inter-fraction adaptive planning did improve the plan quality, but was not strictly required to meet the normal tissue dose planning aims. CONCLUSIONS: The implementation of perineal template-based ISBT treatment without inter-fraction adaptive planning can be delivered to comply with the ABS normal tissue dose guidelines and EMBRACE II limits for prescribed dose.