Development and clinical implementation of SeedNet: A sliding-window convolutional neural network for radioactive seed identification in MRI-assisted radiosurgery (MARS).

PURPOSE: To develop and evaluate a sliding-window convolutional neural network (CNN) for radioactive seed identification in MRI of the prostate after permanent implant brachytherapy. METHODS: Sixty-eight patients underwent prostate cancer low-dose-rate (LDR) brachytherapy using radioactive seeds stranded with positive contrast MR-signal seed markers and were scanned using a balanced steady-state free precession pulse sequence with and without an endorectal coil (ERC). A sliding-window CNN algorithm (SeedNet) was developed to scan the prostate images using 3D sub-windows and to identify the implanted radioactive seeds. The algorithm was trained on sub-windows extracted from 18 patient images. Seed detection performance was evaluated by computing precision, recall, F1 -score, false discovery rate, and false-negative rate. Seed localization performance was evaluated by computing the RMS error (RMSE) between the manually identified and algorithm-inferred seed locations. SeedNet was implemented into a clinical software package and evaluated on sub-windows extracted from 40 test patients. RESULTS: SeedNet achieved 97.6 ± 2.2% recall and 97.2 ± 1.9% precision for radioactive seed detection and 0.19 ± 0.04 mm RMSE for seed localization in the images acquired with an ERC. Without the ERC, the recall remained high, but the false-positive rate increased; the RMSE of the seed locations increased marginally. The clinical integration of SeedNet slightly increased the run-time, but the overall run-time was still low. CONCLUSION: SeedNet can be used to perform automated radioactive seed identification in prostate MRI after LDR brachytherapy. Image quality improvement through pulse sequence optimization is expected to improve SeedNet's performance when imaging without an ERC.

A relationship between environmental pollutants and enteric viruses in mussels(Mytilus galloprovincialis).

Mussels can be affected by environmental contaminants, as non-dioxin-like polychlorinated biphenyls (NDL-PCBs), polycyclic aromatic hydrocarbons (PAHs) and cadmium (Cd). Moreover, mussels may concentrate human enteric viruses, like noroviruses (NoVGI/GII), astrovirus (AsV) and rotavirus (RV). Herein, to establish a relationship between environmental and viral contamination, with the aim to ensure human food safety, both chemical and microbiological analysis were carried out in mussels Mytilus galloprovincialis, farmed in Campania region (Italy). Chemical analysis revealed ranges below the European maximum limits, and were: ∑6 NDL-PCBs (28, 52, 101, 138, 153, 180) 0.579-16.857 ng g-1 wet weight (ww); BaP LOQ (<0.2 µg kg-1)- 2.9 µg kg-1 ww, and ∑4 PAHs (BaA, CHR, BbFA, BaP) 0.7-23.7 µg kg-1 ww; Cd LOQ (<0.005 mg kg-1)- 0.078 mg kg-1 ww. In addition, mussels exhibited a prevalence of NoVGI (18%), NoVGII (43%), AsV (40%), RV (30%) and the presence of more than one viruses resulted in about 35%. Overall, a simultaneous contamination, both chemical and viral, was found in 62% of samples. Interestingly, virus-positive mussels showed levels of chemicals higher than negative ones.

Evaluation of the MIM Symphony treatment planning system for low-dose-rate- prostate brachytherapy.

MIM Symphony is a recently introduced low-dose-rate prostate brachytherapy treatment planning system (TPS). We evaluated the dosimetric and planning accuracy of this new TPS compared to the universally used VariSeed TPS. For dosimetric evaluation of the MIM Symphony version 5.4 TPS, we compared dose calculations from the MIM Symphony TPS with the formalism recommended by the American Association of Physicists in Medicine Task Group 43 report (TG-43) and those generated by the VariSeed version 8.0 TPS for iodine-125 (I-125; Models 6711 and IAI-125A), palladium-103 (Pd-103; Model 200), and cesium-131 (Cs-131; Model Cs-1). Validation was performed for both line source and point source approximations. As part of the treatment planning validation, first a QA phantom (CIRS Brachytherapy QA Phantom Model 045 SN#D7210-3) containing three ellipsoid objects with certified volumes was scanned in order to check the volume accuracy of the contoured structures in MIM Symphony. Then the DICOM data containing 100 patient plans from the VariSeed TPS were imported into the MIM Symphony TPS. The 100 plans included 25 each of I-125 pre-implant plans, Pd-103 pre-implant plans, I-125 Day 30 plans (i.e., from 1 month after implantation), and Pd-103 Day 30 plans. The dosimetric parameters (including prostate volume, prostate D90 values, and rectum V100 values) of the 100 plans were calculated independently on the two TPSs. Other TPS tests that were done included verification of source input and geometrical accuracy, data transfer between different planning systems, text printout, 2D dose plots, DVH printout, and template grid accuracy. According to the line source formalism, the dosimetric results between the MIM Symphony TPS and TG-43 were within 0.5% (0.02 Gy) for r > 1 cm. In the line source approximation validation, MIM Symphony TPS values agreed with VariSeed TPS values to within 0.5% (0.09 Gy) for r > 1 cm. Similarly, in point source approximation validation, the MIM Symphony values agreed to within 1% of the TG-43 and VariSeed values for r > 1 cm. The volume calculations obtained from the MIM Symphony TPS for the CIRS Brachytherapy QA Phantom were within 1% of the actual volume of the phantom. For the clinical cases, the volume and dosimetric parameter calculations for the prostate and rectum did not differ substantially between the pre-implant and Day 30 plans. Overall, our investigations showed negligible differences in dosimetry calculations and planning parameters between the two TPSs. The tests done to check the performance of the MIM Symphony TPS, such as the library data, data transfer, isodose and DVH printout, were found to be satisfactory. On the basis of these results, we conclude that the MIM Symphony TPS can be used as an alternative to the VariSeed TPS for low-dose-rate prostate brachytherapy.

A Novel Positive-Contrast Magnetic Resonance Imaging Line Marker for High-Dose-Rate (HDR) MRI-Assisted Radiosurgery (MARS).

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.

Trace Elements and Persistent Organic Pollutants in Unhatched Loggerhead Turtle Eggs from an Emerging Nesting Site along the Southwestern Coasts of Italy, Western Mediterranean Sea.

Marine pollution is one of the major threats affecting loggerhead turtles, which due to their long life span, highly migratory behavior, and carnivorous diet, may be exposed to elevated levels of toxic elements throughout their life. The transfer of chemicals from mothers to their offspring is of particular conservation concern because it may affect embryonic development and hatching success. In this study, the concentrations of 16 toxic and potentially toxic trace elements, 6 indicator polychlorinated biphenyls (PCBs), and organochlorine pesticide residues (OCPs) were determined in 138 eggs from 46 loggerhead turtle nests laid during the 2021 nesting season in Campania, Italy, western Mediterranean Sea. The possible impact of pollutant levels on hatching success and early embryonic death was also investigated. Trace element analysis was performed using an ICP-MS, except for mercury, which was determined using a Direct Mercury Analyzer® (DMA). PCBs and OCPs were analyzed with high-resolution gas chromatography coupled with high-resolution mass spectrometry (HRGC-HRMS) and gas chromatography tandem quadrupole mass spectrometry GC-MS /MS, respectively. The concentrations of essential elements in the eggs were higher than those of non-essential elements. In addition, the highly chlorinated PCBs (153, 138, and 180) contributed the most to the total PCBs, while OCPs were not detected. No correlations were found between contaminant concentrations and reproductive parameters (hatching success and no obvious embryos). The results obtained suggest that the levels of contaminants found in the eggs do not affect the reproductive success of the species in the study area.

Uncertainty in magnetic resonance imaging-based prostate postimplant dosimetry: Results of a 10-person human observer study, and comparisons with automatic postimplant dosimetry.

PURPOSE: Uncertainties in postimplant quality assessment (QA) for low-dose-rate prostate brachytherapy (LDRPBT) are introduced at two steps: seed localization and contouring. We quantified how interobserver variability (IoV) introduced in both steps impacts dose-volume-histogram (DVH) parameters for MRI-based LDRPBT, and compared it with automatically derived DVH parameters. METHODS AND MATERIALS: Twenty-five patients received MRI-based LDRPBT. Seven clinical observers contoured the prostate and four organs at risk, and 4 dosimetrists performed seed localization, on each MRI. Twenty-eight unique manual postimplant QAs were created for each patient from unique observer pairs. Reference QA and automatic QA were also performed for each patient. IoV of prostate, rectum, and external urinary sphincter (EUS) DVH parameters owing to seed localization and contouring was quantified with coefficients of variation. Automatically derived DVH parameters were compared with those of the reference plans. RESULTS: Coefficients of variation (CoVs) owing to contouring variability (CoVcontours) were significantly higher than those due to seed localization variability (CoVseeds) (median CoVcontours vs. median CoVseeds: prostate D90-15.12% vs. 0.65%, p < 0.001; prostate V100-5.36% vs. 0.37%, p < 0.001; rectum V100-79.23% vs. 8.69%, p < 0.001; EUS V200-107.74% vs. 21.18%, p < 0.001). CoVcontours were lower when the contouring observers were restricted to the 3 radiation oncologists, but were still markedly higher than CoVseeds. Median differences in prostate D90, prostate V100, rectum V100, and EUS V200 between automatically computed and reference dosimetry parameters were 3.16%, 1.63%, -0.00 mL, and -0.00 mL, respectively. CONCLUSIONS: Seed localization introduces substantially less variability in postimplant QA than does contouring for MRI-based LDRPBT. While automatic seed localization may potentially help improve workflow efficiency, it has limited potential for improving the consistency and quality of postimplant dosimetry.

Outcomes after PD-103 versus I-125 for low dose rate prostate brachytherapy monotherapy: An international, multi-institutional study.

BACKGROUND AND PURPOSE: Pd-103 and I-125 are commonly used in low dose rate (LDR) brachytherapy for prostate cancer. Comparisons of outcomes by isotope type are limited, but Pd-103 has distinct radiobiologic advantages over I-125 despite its lesser availability outside the United States. We evaluated oncologic outcomes after Pd-103 vs I-125 LDR monotherapy for prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed databases at 8 institutions for men who received definitive LDR monotherapy with Pd-103 (n = 1,597) or I-125 (n = 7,504) for prostate cancer. Freedom from clinical failure (FFCF) and freedom from biochemical failure (FFBF) stratified by isotope were analyzed by Kaplan-Meier univariate and Cox multivariate analyses. Biochemical cure rates (prostate-specific antigen level ≤ 0.2 ng/mL between 3.5 and 4.5 years of follow-up) by isotype were calculated for men with at least 3.5 years of follow-up and compared by univariate and multivariate logistic regression. RESULTS: Compared with I-125, Pd-103 led to higher 7-year rates of FFBF (96.2% vs 87.6%, P < 0.001) and FFCF (96.5% vs 94.3%, P < 0.001). This difference held after multivariate adjustment for baseline factors (FFBF hazard ratio [HR] = 0.31, FFCF HR = 0.49, both P < 0.001). Pd-103 was also associated with higher cure rates on univariate (odds ratio [OR] = 5.9, P < 0.001) and multivariate (OR = 6.0, P < 0.001) analyses. Results retained significance in sensitivity analyses of data from the 4 institutions that used both isotopes (n = 2,971). CONCLUSIONS: Pd-103 monotherapy was associated with higher FFBF, FFCF, and biochemical cure rates, and suggests that Pd-103 LDR may lead to improved oncologic outcomes compared with I-125.

Levels of non-dioxin-like PCBs (NDL-PCBs) in liver of loggerhead turtles (Caretta caretta) from the Tyrrhenian Sea (Southern Italy).

The levels of six non-dioxin-like polychlorinated biphenyls (PCBs 28, 52, 101, 138, 153, and 180) were determined in the liver of 84 loggerhead turtles (Caretta caretta) stranded along the coasts of the Tyrrhenian Sea in Campania Region (Southern Italy), from 2017 to 2021. The average value of the sum (∑6PCBIND) was 28.0 ± 52.2 ng/g (w.w.). The hexachlorobiphenyls PCB 153 and PCB 138 and the heptachlorobiphenyl PCB 180 were the main contributors to the ∑6PCBIND. A weak positive correlation was found between CCL and highly chlorinated PCBs, with adult females having lower PCB concentrations than juvenile females and adult males. This study provides more comprehensive information on the levels of NDL-PCB in Mediterranean loggerhead turtles and sets the basis for assessing anthropogenic impacts on this species.

Computer-aided segmentation on MRI for prostate radiotherapy, part II: Comparing human and computer observer populations and the influence of annotator variability on algorithm variability.

BACKGROUND AND PURPOSE: Comparing deep learning (DL) algorithms to human interobserver variability, one of the largest sources of noise in human-performed annotations, is necessary to inform the clinical application, use, and quality assurance of DL for prostate radiotherapy. MATERIALS AND METHODS: One hundred fourteen DL algorithms were developed on 295 prostate MRIs to segment the prostate, external urinary sphincter (EUS), seminal vesicles (SV), rectum, and bladder. Fifty prostate MRIs of 25 patients undergoing MRI-based low-dose-rate prostate brachytherapy were acquired as an independent test set. Groups of DL algorithms were created based on the loss functions used to train them, and the spatial entropy (SE) of their predictions on the 50 test MRIs was computed. Five human observers contoured the 50 test MRIs, and SE maps of their contours were compared with those of the groups of the DL algorithms. Additionally, similarity metrics were computed between DL algorithm predictions and consensus annotations of the 5 human observers' contours of the 50 test MRIs. RESULTS: A DL algorithm yielded statistically significantly higher similarity metrics for the prostate than did the human observers (H) (prostate Matthew's correlation coefficient, DL vs. H: planning-0.931 vs. 0.903, p < 0.001; postimplant-0.925 vs. 0.892, p < 0.001); the same was true for the 4 organs at risk. The SE maps revealed that the DL algorithms and human annotators were most variable in similar anatomical regions: the prostate-EUS, prostate-SV, prostate-rectum, and prostate-bladder junctions. CONCLUSIONS: Annotation quality is an important consideration when developing, evaluating, and using DL algorithms clinically.

Computer-aided segmentation on MRI for prostate radiotherapy, Part I: Quantifying human interobserver variability of the prostate and organs at risk and its impact on radiation dosimetry.

BACKGROUND AND PURPOSE: Quantifying the interobserver variability (IoV) of prostate and periprostatic anatomy delineation on prostate MRI is necessary to inform its use for treatment planning, treatment delivery, and treatment quality assessment. MATERIALS AND METHODS: Twenty five prostate cancer patients underwent MRI-based low-dose-rate prostate brachytherapy (LDRPBT). The patients were scanned with a 3D T2-weighted sequence for treatment planning and a 3D T2/T1-weighted sequence for quality assessment. Seven observers involved with the LDRPBT workflow delineated the prostate, external urinary sphincter (EUS), seminal vesicles, rectum, and bladder on all 50 MRIs. IoV was assessed by measuring contour similarity metrics, differences in organ volumes, and differences in dosimetry parameters between unique observer pairs. Measurements from a group of 3 radiation oncologists (G1) were compared against those from a group consisting of the other 4 clinical observers (G2). RESULTS: IoV of the prostate was lower for G1 than G2 (Matthew's correlation coefficient [MCC], G1 vs. G2: planning-0.906 vs. 0.870, p < 0.001; postimplant-0.899 vs. 0.861, p < 0.001). IoV of the EUS was highest of all the organs for both groups, but was lower for G1 (MCC, G1 vs. G2: planning-0.659 vs. 0.402, p < 0.001; postimplant-0.684 vs. 0.398, p < 0.001). Large differences in prostate dosimetry parameters were observed (G1 maximum absolute prostate ΔD90: planning-76.223 Gy, postimplant-36.545 Gy; G1 maximum absolute prostate ΔV100: planning-13.927%, postimplant-8.860%). CONCLUSIONS: While MRI is optimal in the management of prostate cancer with radiation therapy, significant interobserver variability of the prostate and external urinary sphincter still exist.

Fully Balanced SSFP Without an Endorectal Coil for Postimplant QA of MRI-Assisted Radiosurgery (MARS) of Prostate Cancer: A Prospective Study.

PURPOSE: To investigate fully balanced steady-state free precession (bSSFP) with optimized acquisition protocols for magnetic resonance imaging (MRI)-based postimplant quality assessment of low-dose-rate (LDR) prostate brachytherapy without an endorectal coil (ERC). METHODS AND MATERIALS: Seventeen patients at a major academic cancer center who underwent MRI-assisted radiosurgery (MARS) LDR prostate cancer brachytherapy were imaged with moderate, high, or very high spatial resolution fully bSSFP MRIs without using an ERC. Between 1 and 3 signal averages (NEX) were acquired with acceleration factors (R) between 1 and 2, with the goal of keeping scan times between 4 and 6 minutes. Acquisitions with R >1 were reconstructed with parallel imaging and compressed sensing (PICS) algorithms. Radioactive seeds were identified by 3 medical dosimetrists. Additionally, some of the MRI techniques were implemented and tested at a community hospital; 3 patients underwent MARS LDR prostate brachytherapy and were imaged without an ERC. RESULTS: Increasing the in-plane spatial resolution mitigated partial volume artifacts and improved overall seed and seed marker visualization at the expense of reduced signal-to-noise ratio (SNR). The reduced SNR as a result of imaging at higher spatial resolution and without an ERC was partially compensated for by the multi-NEX acquisitions enabled by PICS. Resultant image quality was superior to the current clinical standard. All 3 dosimetrists achieved near-perfect precision and recall for seed identification in the 17 patients. The 3 postimplant MRIs acquired at the community hospital were sufficient to identify 208 out of 211 seeds implanted without reference to computed tomography (CT). CONCLUSIONS: Acquiring postimplant prostate brachytherapy MRI without an ERC has several advantages including better patient tolerance, lower costs, higher clinical throughput, and widespread access to precision LDR prostate brachytherapy. This prospective study confirms that the use of an ERC can be circumvented with fully bSSFP and advanced MRI scan techniques in a major academic cancer center and community hospital, potentially enabling postimplant assessment of MARS LDR prostate brachytherapy without CT.

MRI-assisted radiosurgery: A quality assurance nomogram for palladium-103 and iodine-125 prostate brachytherapy.

PURPOSE: We sought to develop an activity nomogram for magnetic resonance (MR)-planned permanent seed prostate brachytherapy to improve quality assurance through a secondary dosimetric check. METHODS AND MATERIALS: Patients undergoing MRI-assisted radiosurgery (MARS), whereby MRI is used for preoperative planning and postimplant dosimetry, were reviewed from May 2016 to September 2018. Planned activity (U) was fitted by MR-prostate volume (cc) via simple linear regression. Resulting monotherapy nomograms were compared with institutional nomograms from an ultrasound-planned cohort. Dosimetric coverage and external urinary sphincter (EUS) dose were also assessed for MR-planned patients. RESULTS: We identified 183 patients treated with MARS: 146 patients received palladium-103 (103Pd; 102 monotherapy and 44 boost), and 37 received iodine-125 (125I) monotherapy. Median prostate volume was 28 cc (interquartile range: 22-35). Lines of best fit for implant activity were U = 4.344 × (vol) + 54.13 (R2: 95%) for 103Pd monotherapy, U = 3.202 (vol) + 39.72 (R2: 96%) for 103Pd boost and U = 0.684 (vol) + 13.38 (R2: 96%) for 125I monotherapy. Compared with ultrasound, MR-planned nomograms had lower activity per volume (p < 0.05) for both 103Pd monotherapy (∼6%) and 125I monotherapy (∼11%), given a median size (30 cc) prostate. Across all MARS implants, postimplant dosimetry revealed a median V100% of 94% (interquartile range: 92-96%). Median EUS V125 was <1 cc for all patients, regardless of isotope. CONCLUSIONS: We developed a quality assurance nomogram for MR-planned prostate brachytherapy. When compared with ultrasound-planned, MR-planned monotherapy resulted in a lower activity-to-volume ratio while maintaining dosimetric coverage, likely secondary to EUS-sparing and reduced planning target margins.

Development, implementation, and outcomes of a simulation-based medical education (SBME) prostate brachytherapy workshop for radiation oncology residents.

PURPOSE: Despite a preponderance of data demonstrating strong clinical outcomes and cost-effectiveness, prostate brachytherapy use and competency continue to decline. Enhanced resident education may help reverse this trend. We therefore developed and implemented a simulation-based medical education course for low-dose-rate prostate brachytherapy (LDR-PB). MATERIALS AND METHODS: A 1-week LDR-PB course comprised four 1-h lectures on clinical outcomes, physics, radiobiology, and anatomy/contouring, followed by a 4.5-h simulation session on ultrasound-guided prostate phantom implantation, was developed for radiation oncology residents at an academic institution. A 10-statement Likert-scale survey and 20-question multiple-choice test were administered 1 week before and 4 weeks after the course. RESULTS: Precourse and postcourse instruments were completed by 24 and 20 residents, respectively. The median number of prior LDR-PB cases after at least one genitourinary rotation was 10.5 (range 5-20). Overall mean test scores were significantly improved (55% before the course vs 68% after the course; p = 0.010). Mean Likert scores significantly increased on nine of 10 survey statements and were significantly increased overall (2.4 before the course vs 3.3 after the course, p < 0.001). When asked about interest in performing brachytherapy after residency, 37.5% of residents "agreed" or "strongly agreed" before the course vs 50% after the course (p = 0.41). Those with higher postresidency brachytherapy interest (scores of 4-5 vs 1-3) had significantly more LDR-PB cases (11.2 vs 5.3 cases; p = 0.005). CONCLUSIONS: A 1-week simulation-based medical education course for LDR-PB can improve didactic performance and self-reported technical competence/confidence, and may increase overall enthusiasm for brachytherapy. Future studies at our institution will incorporate evaluation of implant quality and assessment of procedural competence into this framework. Residency programs should dedicate resources to this essential component of radiation oncology.

Quality comparison between three-dimensional T2-weighted SPACE and two-dimensional T2-weighted turbo spin echo magnetic resonance images for the brachytherapy planning evaluation of prostate and periprostatic anatomy.

PURPOSE: The purpose of this study was to compare an isotropic three-dimensional (3D) T2-weighted sequence sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with an axial two-dimensional T2-weighted turbo spin echo (TSE) sequence with regard to overall image quality and the delineation of normal prostate and periprostatic anatomy for low-dose-rate prostate cancer brachytherapy planning evaluation. METHODS AND MATERIALS: Patients (n = 69) with prostate cancer who had pelvic magnetic resonance imaging (MRI) for low-dose-rate brachytherapy treatment planning were included. Three radiologists independently assessed the visibility of nine anatomic structures on each sequence by using a 5-point scale and overall image quality by using a 4-point scale. The significance of the differences in diagnostic performance was tested with a Wilcoxon signed rank test. RESULTS: No significant intersequence differences were found for most (7/9) anatomical structures and overall image quality. The mean scores for visibility of anatomical structures on the 3D SPACE and 2D TSE sequences, respectively, were as follows: the zonal anatomy (3.7; 3.9, p = 0.05), prostate capsule (3.9; 4.0, p = 0.08), neurovascular bundle (2.9; 2.9, p = 0.9), rectoprostatic angle (3.8; 3.8, p = 0.35), rectum (4.2; 4.3, p = 0.26), urethra (3.8; 3.9, p = 0.12), urinary bladder (4.6; 4.6, p = 0.61), and overall image quality (2.9; 2.9, p = 0.33). 3D SPACE was superior for delineation of the genitourinary diaphragm (3.8; 3.6, p = 0.003), whereas 2D TSE was superior for delineation of the seminal vesicles (3.5; 4.0, p < 0.0001). CONCLUSIONS: Anatomic delineation of the prostatic and periprostatic anatomy provided by the 3D SPACE sequence is as robust in quality as that provided by a conventional 2D TSE sequence with superior delineation of the genitourinary diaphragm. For MRI-based brachytherapy treatment planning, the 3D SPACE sequence with subcentimeter isotropic resolution can replace the 2D TSE sequence and be incorporated into standard MRI protocols.

Machine Segmentation of Pelvic Anatomy in MRI-Assisted Radiosurgery (MARS) for Prostate Cancer Brachytherapy.

PURPOSE: To investigate machine segmentation of pelvic anatomy in magnetic resonance imaging (MRI)-assisted radiosurgery (MARS) for prostate cancer using prostate brachytherapy MRIs acquired with different pulse sequences and image contrasts. METHODS AND MATERIALS: Two hundred 3-dimensional (3D) preimplant and postimplant prostate brachytherapy MRI scans were acquired with a T2-weighted sequence, a T2/T1-weighted sequence, or a T1-weighted sequence. One hundred twenty deep machine learning models were trained to segment the prostate, seminal vesicles, external urinary sphincter, rectum, and bladder using the MRI scans acquired with T2-weighted and T2/T1-weighted image contrast. The deep machine learning models consisted of 18 fully convolutional networks (FCNs) with different convolutional encoders. Both 2-dimensional and 3D U-Net FCNs were constructed for comparison. Six objective functions were investigated: cross-entropy, Jaccard distance, focal loss, and 3 variations of Tversky distance. The performance of the models was compared using similarity metrics, including pixel accuracy, Jaccard index, Dice similarity coefficient (DSC), 95% Hausdorff distance, relative volume difference, Matthews correlation coefficient, precision, recall, and average symmetrical surface distance. We selected the highest-performing architecture and investigated how the amount of training data, use of skip connections, and data augmentation affected segmentation performance. In addition, we investigated whether segmentation on T1-weighted MRI was possible with FCNs trained on only T2-weighted and T2/T1-weighted image contrast. RESULTS: Overall, an FCN with a DenseNet201 encoder trained via cross-entropy minimization yielded the highest combined segmentation performance. For the 53 3D test MRI scans acquired with T2-weighted or T2/T1-weighted image contrast, the DSCs of the prostate, external urinary sphincter, seminal vesicles, rectum, and bladder were 0.90 ± 0.04, 0.70 ± 0.15, 0.80 ± 0.12, 0.91 ± 0.06, and 0.96 ± 0.04, respectively, after model fine-tuning. For the 5 T1-weighted images, the DSCs of these organs were 0.82 ± 0.07, 0.17 ± 0.15, 0.46 ± 0.21, 0.87 ± 0.06, and 0.88 ± 0.05, respectively. CONCLUSIONS: Machine segmentation of the prostate and surrounding anatomy on 3D MRIs acquired with different pulse sequences for MARS low-dose-rate prostate brachytherapy is possible with a single FCN.

The American Brachytherapy Society prostate brachytherapy LDR/HDR simulation workshops: Hands-on, step-by-step training in the process of quality assurance.

PURPOSE: Education and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician-physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs. METHODS: The ABS, in partnership with industry and academia, has held three radiation oncology team-based LDR/HDR workshops composed of physician-physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop. RESULTS: Of the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR). CONCLUSIONS: The ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years.

Clinical utility and value contribution of an MRI-positive line marker for image-guided brachytherapy in gynecologic malignancies.

PURPOSE: The purpose of this study was to investigate the utility of a novel MRI-positive line marker, composed of C4:S (cobalt chloride-based contrast agent) encapsulated in high-density polyethylene tubing, in permitting dosimetry and treatment planning directly on MRI. METHODS AND MATERIALS: We evaluated the clinical feasibility of the C4:S line markers in nine sequential brachytherapy procedures for gynecologic malignancies, including six tandem-and-ovoid and three interstitial cases. We then quantified the internal resource utilization of an intraoperative MRI-guided procedural episode via time-driven activity-based costing, identifying opportunities for cost-containment with use of the C4:S line markers. RESULTS: The C4:S line markers demonstrated the strongest positive signal visibility on 3D constructive interference in steady state (CISS)/FIESTA-C followed by T1-weighted sequences, permitting accurate delineation of the applicator lumen and thus the source path. These images may be fused along with traditional T2-weighted sequences for optimal tumor and anatomy contouring, followed by treatment planning directly on MRI. By eliminating postoperative CT for fusion and applicator registration from the procedural episode, use of the C4:S line markers could decrease workflow time and lower total delivery costs per procedure. CONCLUSIONS: This analysis supports the clinical utility and value contribution of the C4:S line markers, which permit accurate MRI-based dosimetry and treatment planning, thereby eliminating the need for postoperative CT for fusion and applicator registration.

Prostogram predicted brachytherapy outcomes are not universally accurate: an analysis based on the M. D. Anderson Cancer Center experience with (125)iodine brachytherapy.

PURPOSE: Many clinicians use Prostogram data to advise patients selecting prostate cancer therapy. We examined whether the Prostogram accurately predicted recurrence at 5 years in patients treated with (125)I brachytherapy at 1 tertiary cancer center. MATERIALS AND METHODS: We retrospectively reviewed the records of 208 consecutive patients with prostate cancer treated with a permanent (125)I implant without neoadjuvant androgen deprivation therapy at 1 tertiary cancer center during 1998 to 2006. In each patient the Prostogram brachytherapy formula was used to calculate 5-year biochemical recurrence-free survival probability based on clinical stage, Gleason sum score, prostate specific antigen and the receipt or not of external beam radiotherapy. Recurrence was defined as clinical relapse, death from disease, posttreatment androgen deprivation therapy, secondary treatments administered before prostate specific antigen failure or biochemical recurrence based on the Kattan modification of the American Society for Therapeutic Radiology and Oncology definition of biochemical recurrence after external beam radiation therapy. Patients were divided into quartiles based on Prostogram predicted 5-year recurrence-free survival probability and mean probability was compared to the actual 5-year recurrence-free survival rate in each quartile. Harrell's concordance statistic was used to assess the predictive accuracy of the nomogram. RESULTS: Actual 5-year biochemical recurrence-free survival rates were superior to Prostogram predicted probabilities, including 89% vs 80%, 87% vs 86%, 100% vs 89% and 100% vs 94% in quartiles 1 to 4, respectively. Harrell's concordance value was 0.487 (95% CI 0.369-0.605), indicating that the predictive accuracy of the nomogram in our patients was less than 50%. CONCLUSIONS: The Prostogram did not predict recurrence after permanent prostate brachytherapy in this series. Institutional variability requires that clinicians be cautious when using the Prostogram to counsel patients about the probability of success after permanent prostate brachytherapy.

Is a loose-seed nomogram still valid for prostate brachytherapy in a stranded-seed era?

PURPOSE: To characterize the amount of activity required to treat the prostate with stranded (125)I radioactive seeds and compare our stranded data with the amount of activity recommended when individual seeds are implanted using a Mick applicator. METHODS AND MATERIALS: Data from two groups of patients at The University of Texas M. D. Anderson Cancer Center who were treated with prostate brachytherapy as monotherapy were analyzed. The first group included 100 patients implanted with individual seeds in 2000 and 2001. The second group comprised 81 patients for whom stranded seeds were implanted in 2006 and 2007. Seeds in both groups were (125)I seeds with an air kerma strength of 0.497 U per seed (0.391 mCi per seed). The prescribed dose to planning target volume was 145 Gy. RESULTS: The total implanted activity and the number of seeds used were significantly lower in the second group (p < 0.0001) than in the first group. The reduction in activity in the stranded-seed group was approximately 23% for a 20-cm(3) prostate and approximately 15% for a 60-cm(3) prostate. With equivalent activity between the two groups, the stranded-seed treatment covered a larger treatment volume with the prescribed dose. CONCLUSIONS: The amount of activity required to effectively treat a prostate of a given volume was lower with stranded seeds than with loose seeds. Our experience suggests that prostate brachytherapy that uses stranded seeds leads to a more efficient implant with fewer seeds and lower overall activity, resulting in improved homogeneity.

Comparison of prostate distortion by inflatable and rigid endorectal MRI coils in permanent prostate brachytherapy imaging.

PURPOSE: To study the deformation of the prostate by a rigid reusable endorectal coil and a balloon-type endorectal coil (BTC) during MRI of the prostate in brachytherapy imaging. METHODS AND MATERIALS: The prostate gland was contoured on 157 MRI scans from 52 prostate cancer patients undergoing brachytherapy. The curvature of the posterior prostate surface deformation was computed as a measure of prostate distortion and compared between scans with a BTC, rigid endorectal coil (REC), or no endorectal coil. For the nine patients who had MRIs with all three endorectal scenarios, a mean prostate deformation vector was also calculated between scenarios using deformable image registration. These measures of prostate distortion were compared with the prostate anterior-to-posterior to left-to-right ratio (AP/LR) on the largest prostate axial slice. RESULTS: Significant differences in prostate curvature were found between scans without an endorectal coil versus a REC versus a BTC (p < 0.001). The mean prostate deformation was 3.9 mm due to the BTC and 2.0 mm for the REC (p = 0.012). The mean AP/LR ratio was 0.62 with a BTC versus 0.76 without a coil or 0.73 with a REC (p < 0.001), but no difference existed between scans with a REC versus no coil (p = 0.7). The AP/LR ratio showed moderate correlation with prostate curvature (r = 0.48), and with mean prostate deformation (r = -0.64 to 0.68). CONCLUSIONS: The REC caused minimal deformation of the prostate compared with a BTC with adequate MR image quality, and calculation of the cross-sectional AP/LR ratio on the largest axial prostate slice can serve as a simple measure of prostate distortion.