Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy.

BACKGROUND: Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency. METHODS: An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six "experts" (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts. RESULTS: Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM ( P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) ( P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; ( P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM ( P <0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM ( P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM ( P < 0.001). CONCLUSION: FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.

Fetuin-A adsorption to tunable polydimethylsiloxane and subsequent macrophage response.

Surface modifications can be applied to biomaterials to alter the various surface properties that influence protein-material interactions and the cellular response. The plasma protein fetuin-A has been found to adsorb to many biomaterials but details of its interactions with polydimethylsiloxane (PDMS) and roles in regulating the immune response are not clear. Here, PDMS modifications are achieved by altering the ratio of PDMS formulations to control elastic modulus, and by coating PDMS with polydopamine (PDA) to attach fetuin-A. Surface characterization confirmed that altering the PDMS formulation changed the elastic modulus without affecting surface wetting properties. Surface roughness was measured using atomic force microscopy and surface chemistry was determined using X-ray photoelectron spectroscopy, with only minor changes detected on the softest samples. PDA deposition on PDMS was confirmed and contact angle measurements demonstrated an increase in hydrophilicity. Fetuin-A adsorption was influenced by the PDMS formulations, adsorption changed in a competitive plasma environment, and PDA was able to immobilize the greatest amount of fetuin-A. The inflammatory effects of fetuin-A were investigated, and data suggests that the elastic modulus influences cytokine secretion from macrophages at certain timepoints, a result likely due to varied protein amounts and orientations/conformations in response to material stiffness. The addition of a PDA layer demonstrated the potentially cytokine mitigating effect upon fetuin-A immobilization when compared to unmodified PDMS samples. The results provide new insight into the interactions of fetuin-A with PDMS and PDA, and the potential immune regulatory properties of fetuin-A modified materials.

Unsealed Source: Scope of Practice for Radiopharmaceuticals Among United States Radiation Oncologists.

Purpose: Our purpose was to determine the utilization of and barriers to implementation of radiopharmaceutical therapy (RPT) among U.S. radiation oncologists. Methods and Materials: An anonymous, voluntary 21-item survey directed toward attending radiation oncologists was distributed via social media platforms (Twitter, LinkedIn, Facebook, Student Doctor Network). Questions assessed practice characteristics, specific RPT prescribing patterns, RPT prescribing interest, and perceived barriers to RPT implementation. Nonparametric χ2 test was used for correlation statistics. Results: Of the 142 respondents, 131 (92.3%) practiced in the United States and were included for this analysis. Respondents were well balanced in terms of practicing region, population size served, practice setting, and years in practice. Forty-eight percent (n = 63) reported prescribing at least 1 RPT. An additional 7% (n = 8) participate in RPT administration without billing themselves. Among those that actively prescribed RPT, the mean cumulative cases per month was 4.2 (range, 1-5). The most commonly prescribed radionuclides were radium-223 (40%; mean 2.8 cases/mo), iodine-131 (18%; mean 2.3 cases/mo), yttrium-90 (13%; mean 3.4 cases/mo), "other" (8%), samarium-153 (6%; mean 1.0 cases/mo), and strontrium-89 and phosphorous-32 (2% each; mean 1.8 and 0.4 cases/mo, respectively). Of those who answered "other," lutetium-177 dotatate was most commonly prescribed (8%). No significant (P < .05) association was noted between practice type, practice location, years of practice, or practice volume with utilization of any RPTs. Most radiation oncologists (56%, n = 74) responded they would like to actively prescribe more RPT, although 27% (n = 35) were indifferent, and 17% (n = 22) said they would not like to prescribe more RPT. Perceived barriers to implementation were varied but broadly categorized into treatment infrastructure (44%, n = 57), interspecialty relations (41%, n = 53), lack of training (23%, n = 30), and financial considerations (16%, n = 21). Conclusions: Among surveyed U.S. radiation oncologists, a significant number reported prescribing at least 1 RPT. The majority expressed interest in prescribing additional RPT. Wide-ranging barriers to implementation exist, most commonly interspecialty relations, treatment infrastructure, lack of training, and financial considerations.

Immune Reconstitution Inflammatory Syndrome Complicating Cryptococcal Meningitis in a Pediatric Heart Transplant Patient.

Immune reconstitution inflammatory syndrome can be a complication of cryptococcal meningitis after immune reconstitution from antiretroviral therapy in HIV or reduced immune suppression in transplant recipients. In this case report, the authors discuss the diagnosis and management of cryptococcal-associated immune reconstitution inflammatory syndrome in a 10-year-old pediatric heart transplant recipient.

Validating Modern NRG Oncology Pelvic Nodal and Groupe Francophone de Radiothérapie Urologique Prostate Bed Contouring Guidelines for Post-Prostatectomy Salvage Radiation: A Secondary Analysis of the LOCATE Trial.

PURPOSE: We used the patterns of recurrence on 18F-fluciclovine positron emission tomography (PET)-computed tomography (CT) in patients enrolled in the LOCATE trial after prostatectomy to evaluate how well the most recent NRG Oncology and Groupe Francophone de Radiothérapie Urologique (GFRU) contouring recommendations encompassed all sites of recurrence in the prostate fossa and pelvic nodes in comparison to former Radiation Therapy Oncology Group (RTOG) recommendations. METHODS AND MATERIALS: Patients with biochemically recurrent prostate cancer after radical prostatectomy with a positive finding within the prostate fossa or pelvic nodes on 18F-fluciclovine PET/CTs were identified from the LOCATE patient population. Areas of gross disease were delineated. Prostate fossa contours were delineated using both the 2010 RTOG consensus guidelines and the recently published 2020 GFRU consensus guidelines. Pelvic nodes were contoured with both the 2009 RTOG consensus guidelines and the 2020 NRG consensus guidelines. The performance of the contouring guidelines was assessed by determining what proportion of gross recurrent lesions were encompassed completely or marginally. RESULTS: Of the 213 patients within the LOCATE trial, 45 patients were eligible for analysis with positive 18F-fluciclovine PET findings. Of the 30 total prostate fossa recurrences, the 2010 RTOG contour covered 20 (67%) and missed or marginally covered 10 (33%). The 2020 GFRU contour covered 27 recurrences (90%), and missed or marginally covered 3 (10%). Of the 43 total nodal recurrences, the 2009 RTOG pelvic nodal contour covered 29 nodes (67%), and missed or marginally covered 14 (32%). The 2020 NRG pelvic nodal contour covered 43 nodes (100%), with no misses or marginal coverage. CONCLUSIONS: This secondary analysis of the LOCATE trial exemplifies the improved coverage of the latest prostate fossa contouring recommendations from the GFRU. Similarly, it also validates the updated 2020 NRG pelvic nodal contouring guidelines by demonstrating improved coverage of recurrent disease in this patient population.

Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-ß oligomerizes.

Pleiotropic roles are proposed for brain extracellular vesicles (EVs) in the development of Alzheimer's disease (AD). Our previous studies have suggested a beneficial role for EVs in AD, where the endosomal system in vulnerable neurons is compromised, contributing to the removal of accumulated material from neurons. However, the involvement of EVs in propagating AD amyloidosis throughout the brain has been considered because the amyloid-ß precursor protein (APP), APP metabolites, and key APP cleaving enzymes were identified in association with EVs. Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs isolated from the brains of wild-type and APP overexpressing Tg2576 mice. We found that full-length APP is cleaved in EVs incubated in the absence of cells. The resulting metabolites, both α- and ß-APP carboxyl-terminal fragments and APP intracellular domain accumulate in EVs over time and amyloid-ß dimerizes. Thus, EVs contribute to the removal from neurons and transport of APP-derived neurotoxic peptides. While this is potentially a venue for propagation of the pathology throughout the brain, it may contribute to efficient removal of neurotoxic peptides from the brain.

3-(4-Iodo-phen-yl)-2,3-di-hydro-1H-benzo[f]chromen-1-one.

In the title compound, C19H13IO2, the dihedral angle between the naphthyl ring system and the pendant iodo-phenyl ring is 72.48 (11)°. In the crystal, C-H⋯π inter-actions and I⋯O [3.293 (2) Å] halogen bonds are observed, which combine to generate a herringbone packing motif.

Successful Full-term Pregnancies After High-dose Pelvic Radiotherapy for Ewing Sarcoma: A Case Report.

Survivors of childhood cancer are at risk of long-term sequelae that arise as a consequence of cancer treatment. Radiation and chemotherapy treatment in pediatric female patients can have detrimental impacts on fertility, particularly in those with pelvic tumor involvement. We report 2 successful natural full-term pregnancies with vaginal delivery in a woman 12 years after biopsy, irradiation (55.5 Gy), and multi-agent chemotherapy for treatment of pelvic Ewing sarcoma. Both children were born healthy, with no complications in pregnancy or delivery. Fertility preservation and risk assessment following chemotherapy/radiation therapy is evolving, providing new data to effectively counsel and treat young women.

Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I to IIA Non-Small-Cell Lung Cancer.

PURPOSE: The use of stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality for patients with early-stage non-small-cell lung cancer (NSCLC), with excellent local control rates. Despite this, there is a predominant pattern of distant failure. We sought to identify factors that help predict which patients with stages I to IIA NSCLC treated with SBRT are at highest risk of distant failure, so that we may utilize these factors in the future to help determine which patients may benefit from the addition of systemic therapies. PATIENTS AND METHODS: We retrospectively reviewed 292 patients treated with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients were classified by T stage, tumor size, location and histology, pretreatment positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV), smoking status, and age. The primary endpoint of the study was distant failure. We aimed to analyze if patient characteristics could be identified that predicted for distant failure through the use of competing risk analysis. RESULTS: The median follow-up was 21.9 months. The median dose of radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions (range, 3-13 fractions). The median patient age was 72.8 years (interquartile range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall survival at 2 years was found to be 61.0%. For every 1-year increase in patient age, the hazard of distant failure at any given time was 3% lower (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining characteristics emerged as significant risk factors for distant failure on univariable or multivariable analysis. CONCLUSIONS: Overall, our cohort had distant failure and survival rates comparable with what has been described in the literature. Although we were unable to identify factors outside of age that correlated to risk of distant failure, this topic warrants further investigation, as distant failure is the primary pattern of failure with SBRT when used as the primary management for early-stage NSCLC. Additional molecular studies are needed to further inform on the role of systemic therapy in patients with early-stage NSCLC to improve clinical outcomes.

Reconstructed and Real Proton Radiographs for Image-Guidance in Proton Beam Therapy.

One of the major challenges to proton beam therapy at this time is the uncertainty of the true range of a clinical treatment proton beam as it traverses the various tissues and organs in a human body. This uncertainty necessitates the addition of greater "margins" to the planning target volume along the direction of the beam to ensure safety and tumor target coverage. Proton radiography holds promise as both an image-guidance method for proton beam therapy and as a means of estimating particle beam range in the clinic. In this brief report, we present some of the first real and reconstructed proton radiographs using our particular system. Our qualitative review of these images indicates that this method has excellent potential as a proton radiography-based image guidance system. Based on the encouraging results of our preliminary work, more rigorous and quantitative analyses will be performed shortly and we shall continue to explore the potential of this approach for addressing the particle beam range uncertainty issue.

Interactions of manganese with iron, zinc, and copper in neonatal C57BL/6J and parkin mice following developmental oral manganese exposure.

High dose manganese (Mn) exposure can result in changes in tissue concentrations of other essential metals due to Mn-induced alterations in metal absorption and competition for metal transporters and regulatory proteins. We evaluated responses in mice with a Parkin gene defect (parkin mice) and a wildtype strain (C57BL/6J) following neonatal Mn exposure. Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25 mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. We report liver, femur, olfactory bulb, striatum, and frontal cortex iron, copper, and zinc concentrations and changes in hepatic gene expression of different metal transporters in PND 29 parkin and C57BL/6J mice. A companion manuscript (Foster et al., 2017) [1] describes the primary study findings. This data provides insights into strain differences in the way Mn interacts with other trace metals in mice.