Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival After Stereotactic Ablative Radiation in Oligometastatic Prostate Cancer.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

Cascaded cross-attention transformers and convolutional neural networks for multi-organ segmentation in male pelvic computed tomography.

Purpose: Segmentation of the prostate and surrounding organs at risk from computed tomography is required for radiation therapy treatment planning. We propose an automatic two-step deep learning-based segmentation pipeline that consists of an initial multi-organ segmentation network for organ localization followed by organ-specific fine segmentation. Approach: Initial segmentation of all target organs is performed using a hybrid convolutional-transformer model, axial cross-attention UNet. The output from this model allows for region of interest computation and is used to crop tightly around individual organs for organ-specific fine segmentation. Information from this network is also propagated to the fine segmentation stage through an image enhancement module, highlighting regions of interest in the original image that might be difficult to segment. Organ-specific fine segmentation is performed on these cropped and enhanced images to produce the final output segmentation. Results: We apply the proposed approach to segment the prostate, bladder, rectum, seminal vesicles, and femoral heads from male pelvic computed tomography (CT). When tested on a held-out test set of 30 images, our two-step pipeline outperformed other deep learning-based multi-organ segmentation algorithms, achieving average dice similarity coefficient (DSC) of 0.836±0.071 (prostate), 0.947±0.038 (bladder), 0.828±0.057 (rectum), 0.724±0.101 (seminal vesicles), and 0.933±0.020 (femoral heads). Conclusions: Our results demonstrate that a two-step segmentation pipeline with initial multi-organ segmentation and additional fine segmentation can delineate male pelvic CT organs well. The utility of this additional layer of fine segmentation is most noticeable in challenging cases, as our two-step pipeline produces noticeably more accurate and less erroneous results compared to other state-of-the-art methods on such images.

Clinical VMAT machine parameter optimization for localized prostate cancer using deep reinforcement learning.

BACKGROUND: Volumetric modulated arc therapy (VMAT) machine parameter optimization (MPO) remains computationally expensive and sensitive to input dose objectives creating challenges for manual and automatic planning. Reinforcement learning (RL) involves machine learning through extensive trial-and-error, demonstrating performance exceeding humans, and existing algorithms in several domains. PURPOSE: To develop and evaluate an RL approach for VMAT MPO for localized prostate cancer to rapidly and automatically generate deliverable VMAT plans for a clinical linear accelerator (linac) and compare resultant dosimetry to clinical plans. METHODS: We extended our previous RL approach to enable VMAT MPO of a 3D beam model for a clinical linac through a policy network. It accepts an input state describing the current control point and predicts continuous machine parameters for the next control point, which are used to update the input state, repeating until plan termination. RL training was conducted to minimize a dose-based cost function for prescription of 60 Gy in 20 fractions using CT scans and contours from 136 retrospective localized prostate cancer patients, 20 of which had existing plans used to initialize training. Data augmentation was employed to mitigate over-fitting, and parameter exploration was achieved using Gaussian perturbations. Following training, RL VMAT was applied to an independent cohort of 15 patients, and the resultant dosimetry was compared to clinical plans. We also combined the RL approach with our clinical treatment planning system (TPS) to automate final plan refinement, and creating the potential for manual review and edits as required for clinical use. RESULTS: RL training was conducted for 5000 iterations, producing 40 000 plans during exploration. Mean ± SD execution time to produce deliverable VMAT plans in the test cohort was 3.3 ± 0.5 s which were automatically refined in the TPS taking an additional 77.4 ± 5.8 s. When normalized to provide equivalent target coverage, the RL+TPS plans provided a similar mean ± SD overall maximum dose of 63.2 ± 0.6 Gy and a lower mean rectum dose of 17.4 ± 7.4 compared to 63.9 ± 1.5 Gy (p = 0.061) and 21.0 ± 6.0 (p = 0.024) for the clinical plans. CONCLUSIONS: An approach for VMAT MPO using RL for a clinical linac model was developed and applied to automatically generate deliverable plans for localized prostate cancer patients, and when combined with the clinical TPS shows potential to rapidly generate high-quality plans. The RL VMAT approach shows promise to discover advanced linac control policies through trial-and-error, and algorithm limitations and future directions are identified and discussed.

Identification of a Predictive Genomic Biomarker for Prostate-directed Therapy in Synchronous Low-volume Metastatic Castration-sensitive Prostate Cancer.

BACKGROUND: Standard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC. OBJECTIVE: To evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT. DESIGN, SETTING, AND PARTICIPANTS: We performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated. RESULTS AND LIMITATIONS: A total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study. CONCLUSIONS: Here, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted. PATIENT SUMMARY: In this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation.

Comparison of Multiple Segmentation Methods for Volumetric Delineation of Primary Prostate Cancer with Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment.

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.

Synthetic mucus barrier arrays as a nanoparticle formulation screening platform.

A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris (2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to N-acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.

Induction of double-strand breaks with the non-steroidal androgen receptor ligand flutamide in patients on androgen suppression: a study protocol for a randomized, double-blind prospective trial.

BACKGROUND: Prostate cancer remains the most prevalent malignancy and the second-leading cause of cancer-related death in men in the USA. Radiation therapy, typically with androgen suppression, remains a mainstay in the treatment of intermediate- and high-risk, potentially lethal prostate cancers. However, local recurrence and treatment failure remain common. Basic and translational research has determined the potential for using androgen receptor (AR) ligands (e.g., dihydrotestosterone and flutamide) in the context of androgen-deprived prostate cancer to induce AR- and TOP2B-mediated DNA double-strand breaks (DSBs) and thereby synergistically enhance the effect of radiation therapy (RT). The primary aim of this study is to carry out pharmacodynamic translation of these findings to humans. METHODS: Patients with newly diagnosed, biopsy-confirmed localized prostatic adenocarcinoma will be recruited. Flutamide, an oral non-steroidal androgen receptor ligand, will be administered orally 6-12 h prior to prostate biopsy (performed under anesthesia prior to brachytherapy seed implantation). Key study parameters will include the assessment of DNA double-strand breaks by γH2A.x foci and AR localization to the nucleus. The initial 6 patients will be treated in a single-arm run-in phase to assess futility by establishing whether at least 2 subjects from this group develop γH2A.x foci in prostate cancer cells. If this criterion is met, the study will advance to a two-arm, randomized controlled phase in which 24 participants will be randomized 2:1 to either flutamide intervention or placebo standard-of-care (with all patients receiving definitive brachytherapy). The key pharmacodynamic endpoint will be to assess whether the extent of γH2A.x foci (proportion of cancer cells positive and number of foci per cancer cell) is greater in patients receiving flutamide versus placebo. Secondary outcomes of this study include an optional, exploratory analysis that will (a) describe cancer-specific methylation patterns of cell-free DNA in plasma and urine and (b) assess the utility of serum and urine samples as a DNA-based biomarker for tracking therapeutic response. DISCUSSION: This study will confirm in humans the pharmacodynamic effect of AR ligands to induce transient double-strand breaks when administered in the context of androgen deprivation as a novel therapy for prostate cancer. The findings of this study will permit the development of a larger trial evaluating flutamide pulsed-dose sequencing in association with fractionated external beam RT (+/- brachytherapy). The study is ongoing, and preliminary data collection and recruitment are underway; analysis has yet to be performed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03507608. Prospectively registered on 25 April 2018.

Post-operative Baseplate Radiographic Evaluation Using Routine pre-Operative CT.

Background: There is limited data evaluating post-operative component position and fixation in reverse shoulder arthroplasty (RSA). Therefore, the purpose of this study was to evaluate baseplate position and fixation using routine pre-operative CT and post-operative radiographs. Methods: A retrospective analysis of a series consecutive patient who underwent primary RSA was performed. Pre-operative and post-operative glenoid retroversion and inclination were measured using radiographs aligned with projection silhouettes of 3D scapula models in Mimics software. Baseplate retroversion and inclination were measured followed by evaluating for the presence of radiolucent lines (RLLs). Results: Twenty-four patients met inclusion criteria. The average age was 73.4 ± 10.7 years (range, 45-89 years). Radiographic follow-up was 3.4 ± 1.3 years. Post-operative glenoid baseplate retroversion was 2 ± 10 degrees (range, 30 to -9). Post-operative glenoid baseplate inclination was 3.8 ± 9.1 (range, -13 to 19). Five (21%) RSAs had baseplate retroversion >10 degrees. Follow-up radiographs revealed no RLLs around the baseplate, central post, or peripheral screws in any patient. Conclusions: Pre-operative CT imaging enabled evaluation of baseplate component placement and fixation on post-operative radiographs. Baseplate version was within 10 degrees of neutral in 79% (19/24) of patients. No RLLs or loss of fixation were found in any cases. Level of Evidence: Level IV: Diagnostic Study.

Effect of Transperineal Versus Transrectal Prostate Biopsy on the Quality of Hydrogel Spacer Placement in Men Prior to Radiation Therapy for Prostate Cancer.

OBJECTIVE: To determine whether prostate biopsy type affects spacer placement quality using a large sample of patients treated in the ambulatory setting. METHODS: A retrospective cohort study was conducted on patients diagnosed with prostate cancer who underwent hydrogel spacer placement before primary radiation treatment between 2018 and 2023 after transperineal (TP) or transrectal (TR) prostate biopsy. Study outcomes were Spacer Quality Score (SQS) (0-2, with greater values indicating better placement), Rectal Wall Infiltration (RWI) (0-3, with lower values indicating lack of RWI), and the occurrence of other hydrogel complications. RESULTS: A total of 395 patients were included. A pre-hydrogel TR biopsy was performed in 273 patients (69.1%), while TP biopsy was performed in 122 (30.9%). A SQS ≥1 occurred in 308 (77.9%) patients. A greater proportion of TP patients had a favorable SQS (≥1) compared to those who underwent TR (87.7 vs 73.5%, P <.002). An RWI score ≥2 was found in 180 (45.6%) patients. The proportion of patients with an unfavorable RWI score (≥2) did not differ significantly by type of biopsy performed. Patients who had an interval of >70 days between biopsy and hydrogel placement had significantly decreased odds of an RWI score ≥2 (odds ratio = 0.42, 95% confidence interval: 0.21-0.83). Only one infection was found after hydrogel placement. CONCLUSION: The quality of hydrogel placement was significantly better in men who had undergone TP biopsy. Rectal wall infiltration was more common than previously reported but did not differ between TP and TR biopsies.

Prediction of isometric forces from combined epidural spinal cord and neuromuscular electrical stimulation in the rat lower limb.

Both epidural spinal cord and muscle stimulation have been widely used for restoration of movement after spinal cord injury. However, using both approaches simultaneously could provide more flexible control compared to using either approach alone. We evaluate whether responses evoked by combined spinal and muscle stimulation can be predicted by the linear summation of responses produced by each individually. Should this be true, it would simplify the prediction of co-stimulation responses and the development of control schemes for spinal cord injury rehabilitation. In anesthetized rats, we measured hindlimb isometric forces in response to spinal and muscle stimulation across a range of amplitudes. Force prediction errors were calculated as the difference between predicted co-stimulation vectors and observed co-stimulation vectors whereby small errors signified evidence for linear summation. We found that the errors for spinal and muscle co-stimulation were significantly larger than expected. Using a bootstrapping analysis, we find that these larger errors do not reflect a nonlinear interaction between spinal and muscle responses. Instead, they can be attributed to the variability of spinal stimulation responses. We discuss the implications of these results to the use of combined muscle and spinal stimulation for the restoration of movement following spinal cord injury.

Minimally Invasive Distal Biceps Tendon Reconstruction With Semitendinosus Allograft and Dual Unicortical Button Fixation.

Complete rupture of the distal biceps tendon is routinely treated with direct repair; however, chronic, mid-substance, or musculotendinous tears are challenging clinical scenarios for surgeons. Although attempts at direct repair should be considered, in cases of severe retraction or tendon deficiency, a reconstruction may be warranted. Herein the authors describe a technique for distal biceps reconstruction using allograft with a Pulvertaft weave via a standard anterior incision, similar to primary repair, with a small catchment incision more proximally for tendon retrieval. Use of this technique with dual unicortical buttons allows for early range of motion, restoration of the distal footprint, and improved biomechanical construct strength, which has proven invaluable in a population of elite and highly active military servicemembers.

Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology.

Histopathology and clinical staging have historically formed the backbone for allocation of treatment decisions in oncology. Although this has provided an extremely practical and fruitful approach for decades, it has long been evident that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. As efficient and affordable DNA and RNA sequencing have become available, the ability to provide precision therapy has become within grasp. This has been realized with systemic oncologic therapy, as targeted therapies have demonstrated immense promise for subsets of patients with oncogene-driver mutations. Further, several studies have evaluated predictive biomarkers for response to systemic therapy within a variety of malignancies. Within radiation oncology, the use of genomics/transcriptomics to guide the use, dose, and fractionation of radiation therapy is rapidly evolving but still in its infancy. The genomic adjusted radiation dose/radiation sensitivity index is one such early and exciting effort to provide genomically guided radiation dosing with a pan-cancer approach. In addition to this broad method, a histology specific approach to precision radiation therapy is also underway. Herein we review select literature surrounding the use of histology specific, molecular biomarkers to allow for precision radiotherapy with the greatest emphasis on commercially available and prospectively validated biomarkers.

Children with Rolandic epilepsy have micro- and macrostructural abnormalities in white matter constituting networks necessary for language function.

INTRODUCTION: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS. METHODS: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing. RESULTS: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036). CONCLUSION: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder.

Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.

Improving visualization in shoulder arthroscopy.

Arthroscopic shoulder procedures are one of the most common procedures used to restore function through minimally invasive techniques. With the demand for shoulder arthroscopic procedures comes the need for safe, effective, and efficient surgery that maximizes patient outcomes while minimizing complications. Many variables contribute to visualization in shoulder arthroscopy including vascular anatomy, blood pressure control, arthroscopic pump systems, turbulence control, epinephrine, and tranexamic acid. Furthermore, patient positioning can have a dramatic effect on visualization with both the beach chair position and lateral decubitus positioning having various strengths and weaknesses depending on the intended procedure being performed. The purpose of this review is to examine the benefits and complications reported in the literature for improving visualization in shoulder arthroscopy.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Improving Quality Metrics in Radiation Oncology: Implementation of Pretreatment Peer Review for Stereotactic Body Radiation Therapy in Patients with Thoracic Cancer.

Purpose: Traditional peer reviews occur weekly, and can take place up to 1 week after the start of treatment. The American Society for Radiation Oncology peer-review white paper identified stereotactic body radiation therapy (SBRT) as a high priority for contour/plan review before the start of treatment, considering both the rapid-dose falloff and short treatment course. Yet, peer-review goals for SBRT must also balance physician time demands and the desire to avoid routine treatment delays that would occur in the setting of a 100% pretreatment (pre-Tx) review compliance requirement or prolonging the standard treatment planning timeline. Herein, we report on our pilot experience of a pre-Tx peer review of thoracic SBRT cases. Methods and Materials: From March 2020 to August 2021, patients undergoing thoracic SBRT were identified for pre-Tx review, and placed on a quality checklist. We implemented twice-weekly meetings for detailed pre-Tx review of organ-at-risk/target contours and dose constraints in the treatment planning system for SBRT cases. Our quality metric goal was to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. We used a statistical process control chart with sigma limits (ie, standard deviations [SDs]) to access compliance rates with pre-Tx review implementation. Results: We identified 252 patients treated with SBRT to 294 lung nodules. When comparing pre-Tx review completion from initial rollout to full implementation, our rates improved from 19% to 79% (ie, from 1 sigma limit [SDs]) below to >2 sigma limits (SDs) above. Additionally, early completion of any form of contour/plan review (defined as any pre-Tx or standard review completed before exceeding 25% of the dose delivered) increased from 67% to 85% (March 2020-November 2020) to 76% to 94% (December 2020-August 2021). Conclusions: We successfully implemented a sustainable workflow for detailed pre-Tx contour/plan review for thoracic SBRT cases in the context of twice-weekly disease site-specific peer-review meetings. We reached our quality improvement objective to peer review ≥90% of SBRT cases before exceeding 25% of the dose delivered. This process was feasible to conduct in an integrated network of sites across our system.

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.