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OBJECTIVE The aim of this study was to evaluate mortality and progression outcomes in patients undergoing stereotactic radiosurgery (SRS) for breast cancer brain metastases and to identify associated risk factors using a national quality registry. METHODS The NeuroPoint Alliance (NPA) SRS Registry was employed for this study, which conducted prospective enrollment of patients undergoing SRS at 16 participating centers from 2017 to 2024. Outcomes of interest included the post-SRS EQ-5D score change, overall survival, local progression, out-of-field progression, and overall intracranial progression. For all time-to-event analyses, Kaplan-Meier curves and multivariable Cox regressions with hazard ratios were used. RESULTS A total of 138 patients (127 female, mean age 59.8 years) were identified; 46.4% had a single lesion, 42.0% had 2–4 lesions, and 11.6% had ≥ 5 lesions, while 87.0% had a Karnofsky Performance Status (KPS) score between 80 and 100. The median overall survival was 17.9 months, and independent predictors of all-cause mortality included a KPS score ≤ 90 (HR 6.73) and diabetes mellitus (HR 3.35). The median time to local progression was 19.8 months. More than 5 lesions at baseline (HR 9.03) and a marginal dose ≤ 17.6 Gy (HR 8.00) were predictive of local recurrence. The median was not reached for out-of-field progression, and predictors included ≥ 2 lesions at the time of SRS (HR 3.20) and a marginal dose ≤ 17.6 Gy (HR 4.61). At the final follow-up assessment, 17.1% of patients experienced no change according to the EQ-5D, while 34.3% had improvement, 11.4% had mixed results, and 37.1% had worsened health. In the multivariable linear regression model, pre-SRS resection (r = 1.92) and baseline EQ-5D score (r = 1.29) were statistically significant predictors of quality of life at the final follow-up assessment. CONCLUSIONS Using real-world data from the NPA SRS Registry, this study demonstrated comparable outcomes in patients who underwent SRS for breast cancer brain metastases compared with those of previous literature. The number of lesions at the time of SRS and the marginal dose were independent risk factors for local recurrence, out-of-field progression, and overall intracranial progression. Pre-SRS resection and baseline EQ-5D score were independent predictors of quality of life following SRS.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

AbstractNeuroendocrine neoplasms (NENs) with peritoneal metastases (PM) represent a complex clinical challenge because of low incidence and heterogeneous phenotypes. This commentary describes the results of a national consensus aimed at addressing clinical management of patients with NENs and PM. An update of the 2018 Chicago consensus guidelines was conducted with a modified Delphi technique, which encompassed two rounds of voting. The levels of agreement for various pathway blocks were assessed, and key systemic therapy concepts were summarized by content experts. Supporting evidence was evaluated via a rapid literature review. Overall, the level of evidence for the management of PM in this disease was universally low. In total, 107 participants responded in the first round, with 88 of 107 (82%) participating in the second round. Strong consensus (>90%) was achieved in five of seven (71%) and seven of seven (100%) blocks in rounds 1 and 2, respectively. A multidisciplinary approach including psychosocial and wellness assessments received a strong positive recommendation. Management of NENs with PM was organized according to disease grade and symptom profiles. In grade 1 and 2 well‐differentiated NENs, cytoreductive surgery received strong support (>95%) after the management of functional syndromes (if present). For grade 3 well‐differentiated NENs, systemic therapy is the primary recommendation, with surgical resection considered in select cases. Given the limited evidence, the consensus‐driven clinical pathway offers vital clinical guidance for the management of NENs with PM. The need for high‐quality evidence remains critical to the field.

Background: Autonomic dysfunction is common after spinal cord injury (SCI). There are currently limited tools to comprehensively characterize its deficits. While individual established autonomic tests have a long history and sound scientific background, translating these autonomic testing results to inform clinical understanding is a major barrier. Objectives: To assess a strategic battery of autonomic tests to characterize and act as a biomarker of autonomic regulation for individuals with SCI and to develop a novel graphical representation of these data to facilitate understanding of autonomic dysfunction after SCI. Methods: We outline a battery of six laboratory autonomic tests that were curated to collectively describe the ability of individuals with SCI to inhibit and recruit sympathetic activity through the injured spinal cord. Heart rate/blood pressure variability, bolus phenylephrine, hand and foot cold pressor, Valsalva maneuver, and bladder pressor are herein described. Incorporating normative control data for 30 uninjured individuals completing this testing battery, we further demonstrate the utility of a composite biomarker, comparing these control results to 11 individuals with SCI. Results: Results demonstrate strong normality of data with testing psychometrics, suggesting stable reproducibility with repeat testing. Even in this preliminary sample of individuals with SCI, clear differences begin to emerge compared to uninjured norms. This illustrates the ability of this collective testing battery to characterize autonomic regulation after SCI. To aid in clinical translation, we further present a graphical representation, an autonomic phenotype , which serves as a snapshot of how normal or abnormal sympathetic inhibition and recruitment of activation may be after SCI. Conclusion: Utilizing these autonomic phenotypes, three example cases of individuals with SCI highlight evidence of varied degrees of autonomically complete SCI. Together, this represents a key advancement in our understanding of autonomic function after SCI.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

Introduction Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a high 5-year survival rate of approximately 98%. Despite advances in diagnosis and treatment, up to 20% of patients experience recurrence, adversely affecting their quality of life. Predictive models have been developed to assess recurrence risk and guide clinical decision-making, but these models often face limitations such as retrospective design, lack of diversity in study populations and absence of external validation. The primary aim is to externally validate existing predictive models for DTC recurrence using prospective data from a diverse Latin American cohort. The secondary aim is to explore opportunities for model recalibration to improve their performance in our population. Methods and analysis The CaTaLiNA study is a multicentre prospective observational study conducted across 10 hospitals in five Latin American countries, including Ecuador, Peru, Uruguay and Mexico. Patients aged 18 years or older receiving treatment for DTC, such as the first thyroid surgery, active surveillance or radiofrequency ablation will be included. Recruitment will occur from November 2023 to June 2025, with follow-up extending until June 2028. Data collection will include baseline clinical, surgical and histological characteristics, treatment details and follow-up outcomes. Statistical analysis will follow the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis guidelines, using imputation strategies for missing data and evaluating calibration and discrimination of the prediction models. Calibration measures include the ratio of expected and observed events, calibration slope and calibration plot, while discrimination will be assessed using the C-index and area under the receiver operating characteristic curve. Ethics and dissemination This study protocol was approved by Comité de Ética de Investigación en Seres Humanos de la Universidad San Francisco de Quito USFQ ‘CEISH-USFQ’ APO-010–2023-CEIHS-USFQ Oficio No. 161-2023-CA-23030M-CEISH-USFQ. Results will be disseminated via peer-reviewed publications.

Objectives: This practice parameter was revised collaboratively by the American College of Radiology (ACR), and American Radium Society (ARS). Image-guided radiation therapy (IGRT) uses various imaging modalities to maximize the accuracy and precision of radiation treatment delivery. Methods: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters–Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Results: This practice parameter for IGRT addresses qualifications and responsibilities of personnel, clinical IGRT implementation, documentation, quality control and improvement, safety, and patient education. Since the publication of the ACR–ASTRO Practice Parameter in 2019, there is now more clarity as to what criteria and parameters need to be documented in the medical record, a better appreciation of the large amount of imaging data, how to interpret such data, as well as the complex interactions of multiple systems in the implementation of IGRT. Conclusions: This practice parameter assists practitioners in the clinical use of IGRT. IGRT should complement and be used in combination with other quality assurance processes. IGRT is a rapidly evolving field, and practitioners should have a thorough understanding of its strengths and potential limitations.

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.

Abstract Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder infrequently complicated by delayed-onset pituitary disease. A 41-year-old female presented with papular, acneiform skin lesions. Shave biopsy demonstrated a superficial dermal epithelioid cell proliferation with S100, CD1a, and langerin positivity on immunohistochemistry and a BRAF p.N486_P490del inframe deletion-gain of function pathogenic variant on next-generation sequencing. The skin lesions spontaneously resolved. One year later, she developed progressive fatigue, fevers, anorexia, menstrual irregularities, polyuria, and polydipsia. Laboratory workup was consistent with panhypopituitarism. Pituitary magnetic resonance imaging noted mass-like thickening and enhancement of the infundibulum extending toward the hypothalamus. After treatment with cobimetinib, magnetic resonance imaging findings resolved but endocrinopathies persisted, requiring indefinite hormone therapy. This case demonstrates the full spectrum of endocrinopathies of LCH-induced pituitary disease and is an unusual circumstance of LCH with delayed-onset panhypopituitarism.

Abstract Objective This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS). Methods Infants aged 2–24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high‐dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis. Treatment groups included hormonal therapy followed by vigabatrin (reference), hormonal‐to‐hormonal, hormonal‐to‐nonstandard, vigabatrin‐to‐hormonal, and vigabatrin‐to‐nonstandard. Nonstandard treatments included other antiseizure medications and dietary therapy. Treatment groups were tested for differences in 3‐month clinical remission using a binary logistic regression to estimate odds ratios (ORs). Results There were 153 infants with IESS who received second treatments. The highest rates of 3‐month remission were among infants in the hormonal‐to‐vigabatrin (22/65, 34%) and vigabatrin‐to‐hormonal (9/26, 35%) groups, followed by vigabatrin‐to‐nonstandard (3/10, 30%), hormonal‐to‐hormonal (4/22, 18%), and hormonal‐to‐nonstandard (1/30, 3.3%). Compared to the hormonal‐to‐vigabatrin group (reference), fewer infants had remission in the hormonal‐to‐nonstandard group (OR = .07, 95% confidence interval [CI] = .01–.53), and there was a trend toward fewer infants in the hormonal‐to‐hormonal group (OR = .43, 95% CI = .13–1.4, p = .17). Following initial hormonal treatment, the number needed to treat was three infants for one additional infant to have remission when treated with vigabatrin compared to nonstandard therapy as the second treatment. Significance This updated analysis with an expanded sample size provided power for additional subgroup analysis. Overall response rates were low, and at best only one third had remission after second treatment. Results support a clinical strategy of switching mechanism of action when selecting a second medication for epileptic spasms (i.e., use vigabatrin after hormonal therapy, or hormonal therapy after vigabatrin). Our findings also support the use of standard over nonstandard therapies.