Citations

Abstract Background: Solitary fibrous tumors (SFT) make up less than 5% of sarcomas. The Demicco model stratifies risk of metastasis based on age, tumor size, mitotic count, and necrosis. Patients (pts) with relapsed disease have limited options. We evaluated outcomes of systemic therapies (tx) to treat SFT. Methods: A retrospective analysis was performed of pts with intermediate-to-high risk SFT confirmed by soft tissue pathologists at a multi-site health system from 1999 – 2024. Demographics, tx, and pt outcomes were analyzed. Radiographic response was abstracted from documentation by treating provider. Results: Sixty pts had intermediate-to-high risk SFT, of which 21 pts received systemic tx. Of these, 12 were male, median age at diagnosis 62.8 years (41.0 – 82.7 yrs). Tumors originated from chest (11, 52.4%), abdomen (5, 23.8%), pelvis (4, 19.0%), and skull (1, 4.8%). All pts had surgery for primary tumor, median size 16.0 cm (7.8 – 43.0), and 14 (66.7%) had surgery at relapse. Eight pts (38.1%) had perioperative radiation therapy (RT); 12 (57.1%) had palliative RT. Five (23.8%) had ablation. Of the 21 pts, 2 (9.5%) had perioperative chemotherapy (chemo). Twenty pts (95.2%) received median 2 lines (1 – 6) of palliative systemic tx (1 pt did not pursue any). One pt had partial response on dacarbazine, otherwise best clinical response was stable disease (SD, 53.1% vascular endothelial growth factor inhibitors (VEGFi), 40% chemo) or disease progression (PD). Most pts received VEGFi: 11 pts had sunitinib (median 3.1 months, range 1.0 – 10.6 mo), 11 pts had pazopanib (4.1 mo, 0.1 – 38.7), and 10 pts had temozolomide/bevacizumab (5.6 mo, 1.0 – 15.8). VEGFi was dose reduced or held in 59.4% . Discontinuation due to toxicity occurred in 34.4% of pts treated with VEGFi vs 26.7% of pts treated with chemo. Five pts received liposomal doxorubicin (median 4.8 mo, range 3.5 – 11.3). Four pts had doxorubicin with dacarbazine, ifosfamide or olaratumab (2.8 mo, 0.7 – 8.5). Two pts received dacarbazine (1.9 and 9.6 mo, respectively), and 2 pts received gemcitabine/docetaxel (0.9 and 4 mo). Eribulin and trabectedin (1 pt, respectively) were used for less than 1 mo. Tx was held or dose reduced for 1 pt on doxorubicin/dacarbazine and 1 pt on gemcitabine/docetaxel. Three pts had immunotherapy (IO, 2 pts pembrolizumab, 1 pt nivolumab/ipilimumab) and stopped for PD (2 pts) or toxicity (1 pt) after 2 mo or less. Two pts participated in clinical trials. Median time from primary surgery to relapse was 2.0 yrs (0.0 – 12.3). Sixteen pts died (76.2%), 14 from SFT. Median time from relapse to death or last contact was 4.1 yrs (0.5 – 14.7). Median overall survival from diagnosis to death/last contact was 6.6 yrs (0.6 – 27.0). Conclusion: Perioperative chemo was rarely used to treat intermediate-to-high risk SFT. For relapse, VEGFi use was more common than chemo, with more pts achieving SD and receiving longer duration of tx. VEGFi had greater toxicity and subsequent discontinuation. No benefit was observed in few pts who received IO. Clinical trial participation was uncommon. Citation Format: Miranda Lin, Brittany Siontis, Steven Robinson, Scott Okuno, Thanh Ho. Systemic Therapy and Outcomes in Patients with Intermediate or High-Risk Solitary Fibrous Tumor [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr B054.

ABSTRACT Objective Weight loss is frequently considered a cardinal presenting symptom for patients with Zenker diverticulum (ZD). We hypothesized that weight loss in patients with cricopharyngeal muscle dysfunction (CPMD), with or without diverticula, was associated with the length of symptoms and size of diverticulum. Methods Prospective, multicenter observational study of CPMD patients with and without diverticula reporting unintentional weight loss (+WL) or no weight loss (−WL) prior to enrollment in the Prospective Outcomes of Cricopharyngeal Hypertonicity (POuCH) database. Complications and symptom response using a patient reported outcome measure, the Eating Assessment Tool (EAT‐10), were compared. Results Of 427 patients, 101 (23.6%) were +WL. Median weight loss was 14 pounds (interquartile range [IQR] 10–25). +WL cohort had a mean age of 71.5 (standard deviation [SD] 11.5) vs. 67.9 in −WL (SD 11.6, p = 0.007). Mean preoperative EAT‐10 score was 24.7 in +WL (SD 9.7) and 14.8 in −WL (SD 8.8, p < 0.0001). Higher preoperative weight loss was associated with higher preoperative EAT‐10 ( p < 0.0001, Spearman's ρ = 0.43). Size of diverticulum was associated with WL ( p = 0.003), but weight loss was highest in both large diverticula and CP bars. Duration of symptoms was not associated with weight loss ( p = 0.30). Postoperative complications in +WL and −WL patients were similar ( p = 0.78). Conclusion Unintentional weight loss is common with ZD. Patients with worse dysphagia are more likely to have more weight loss. Weight loss does not increase with the size of the diverticulum or length of symptoms. Surgery has a similar safety profile with greater improvement in dysphagia in patients reporting weight loss. Level of Evidence 3.

Abstract This article summarizes data for 13 investigational treatments for which at least preliminary seizure outcome data in patients with epilepsy were reported at the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices held in Madrid, Spain, on May 3–6, 2026. The treatments reviewed include bexicaserin, a selective 5‐hydroxytryptamine (5‐HT, serotonin) type 2C (5‐HT 2C ) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB‐101, a selective 5‐HT 2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early‐onset SCN2A ‐DEE; EPX‐100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5‐HT 2A and 5‐HT 2B receptors, repurposed as a treatment for DEEs; ES‐481, an antagonist of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP‐γ8), under investigation for the treatment of drug‐resistant epilepsy; ETX‐101, a gene therapy in development for the treatment of SCN1A ‐positive Dravet syndrome; PrevEp‐006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A (SV2A) ligand under investigation as an acute seizure rescue therapy; radiprodil, a negative allosteric modulator that binds to the GluN2B subunit of the N ‐methyl‐ D ‐aspartate (NMDA) receptor, in development for the treatment of seizures and other symptoms associated with GRIN‐related neurodevelopmental disorder, tuberous sclerosis complex, and focal cortical dysplasia type II; RAP‐219, a selective negative allosteric modulator of TARP‐γ8, in development for drug‐resistant focal epilepsy; relutrigine, a selective disease‐state sodium channel modulator investigated as a treatment for SCN2A ‐ and SCN8A ‐DEE; Staccato Alprazolam, a breath‐actuated device that delivers alprazolam to the lungs for rapid seizure termination; vormatrigine, a functionally selective sodium channel modulator in development for the treatment of focal seizures; and zorevunersen, an antisense oligonucleotide engineered to restore endogenous Nav1.1 protein expression, investigated for the treatment of Dravet syndrome. Overall, the evidence reviewed justifies expectations for improved health outcomes for the millions of children and adults with epilepsy who do not fully benefit from existing therapies.

Abstract Over the last 34 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided an interactive forum for stakeholders to discuss investigational and recently licensed treatments for seizures and epilepsy. The Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII) took place in Madrid, Spain, on May 3–6, 2026. This article provides summaries of eight treatments in preclinical and early clinical development that were presented at EILAT XVIII. These include AUT00206, a positive allosteric modulator of Kv3.1 and Kv3.2 voltage‐gated potassium channels in development for the treatment of rare epilepsy syndromes as well as neurodevelopmental and neuropsychiatric disorders; ION283, an antisense oligonucleotide designed to suppress the expression of glycogen synthase 1, under investigation for the treatment of Lafora disease; MSCA‐7136, a selective allosteric RAS/mitogen‐activated protein kinase—extracellular signal regulated kinase (MEK) inhibitor being developed for the treatment of focal seizures associated with mesial temporal lobe epilepsy and seizures associated with tuberous sclerosis complex; OV329, a selective inhibitor of γ‐aminobutyric acid (GABA) aminotransferase, in development for the treatment of drug‐resistant focal seizures; PTI5803 (probenecid), an uricosuric agent and a blocker of pannexin 1 channels, repurposed as a treatment for seizures associated with focal cortical dysplasia; simufilam, a filamin A modulator under investigation for the treatment of tuberous sclerosis complex‐related epilepsy; SN‐2000, a selective allosteric phosphodiesterase 4B inhibitor, in development for the treatment of focal seizures; and sodium selenate, a promoter of the dephosphorylation of pathological hyperphosphorylated tau in the brain, under investigation as a disease‐modifying agent in mesial temporal lobe epilepsy. Treatments in more advanced clinical development are discussed in an accompanying article.

Abstract Aims Nutritional counselling is a core component of cardiac rehabilitation (CR), yet the evidence base for specific dietary interventions within CR remains fragmented. This scoping review aimed to map the range of nutritional interventions evaluated in adult CR programmes, characterize their reported outcomes, and identify key gaps in current evidence and practice. Methods and results Following the Arksey and O’Malley framework and reporting according to PRISMA-ScR, a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception to June 2026. Eligible studies included randomized controlled trials, non-randomized trials, and observational studies evaluating an explicitly described nutritional intervention within a structured CR programme in adults with established cardiovascular disease. Of 2765 identified records, 35 studies met eligibility criteria. Interventions spanned Mediterranean and heart-healthy dietary patterns, calorie-restriction and weight-loss programmes, comprehensive lifestyle interventions, structured nutrition education and counselling, supplementation, functional foods, and individualized diet prescriptions. Across categories, improvements in body weight, central adiposity, and adherence to cardioprotective dietary recommendations were commonly reported, particularly when nutrition was delivered with repeated contact and individualized support. Effects on lipid profiles, inflammatory markers, blood pressure, functional capacity, and clinical outcomes were more variable. Conclusion Nutritional interventions within CR were most consistently associated with improvements in intermediate behavioural, anthropometric, and cardiometabolic outcomes, particularly when structured and reinforced over time. However, heterogeneity in study design, intervention delivery, comparator groups, outcome reporting, and follow-up duration precludes definitive conclusions about comparative efficacy, optimal intervention format, or the magnitude of benefit. Greater standardization, longer follow-up, and further evaluation of personalized nutritional strategies are needed to strengthen the nutritional component of CR.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) &lt;0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend&lt;0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

ABSTRACT We examined the prognostic value of routine NGS data in newly diagnosed acute myeloid leukemia (AML) treated with intensive (7 + 3 backbone) induction, specified by AML subtype. A contemporary (2015–2025) series of 545 Mayo Clinic patients (median age 56 years, females 44%) was considered. Median follow‐up was 49 months with 341 (63%) allogeneic hematopoietic stem cell transplantations (AHSCT) recorded. AML subtypes included core‐binding factor (CBF; N = 72; 13%), primary non‐CBF ( N = 403; 74%), post‐myelodysplastic syndromes (MDS) or post‐myelodysplastic/myeloproliferative neoplasms (post‐MDS‐MDS/MPN; N = 28; 5%), post‐MPN ( N = 15; 3%), and therapy‐related (t‐AML; N = 27; 5%). Corresponding complete remission rates, with/without count recovery (CR/CRi), were 89%, 76%, 64%, 27%, and 78% ( p < 0.01) and 5‐year transplant‐censored survival rates 68%, 57%, 21%, 0%, and 55% ( p < 0.01). In multivariable analyses, the prognostic value of specific mutations was mostly limited to primary non‐CBF AML where adverse karyotype (OR 1.9; p = 0.04) predicted inferior and FLT3 ‐ITD (OR 0.4; p < 0.01) or NPM1 MUT / FLT3 WT (OR 0.1; p < 0.01) superior CR/CRi while KRAS MUT (HR 8.8; p < 0.01), TP53 MUT (HR 5.4; p < 0.01), and TET2 MUT (HR 2.3; p = 0.01) predicted inferior and NPM1 MUT / FLT3 WT (HR 0.3; p = 0.01) superior survival. Prognostication in intensively‐treated AML should start with subtype specification and recognition of the limited value of NGS in non‐primary AML. Post‐MPN AML is particularly associated with dismal outcomes and should be prognostically distinguished from post‐MDS‐MDS/MPN AML. In primary non‐CBF AML, in addition to previously established risk factors, the favorable impact of FLT3 ‐ITD on achieving CR/CRi and the unfavorable impact of KRAS MUT and TET2 MUT on transplant‐censored survival were noted and require confirmation from additional studies.

Abstract Summary The proliferation of pathogen bioinformatics pipelines has outpaced the community’s ability to compare them on common ground. Self-reported performance numbers, ad-hoc evaluation datasets, and inconsistent metrics make pipeline selection difficult for clinical and public-health researchers. We present PathoBench , an open web platform that addresses this gap through three coordinated mechanisms: (i) a curated registry of 26 standard benchmark datasets across 10 human pathogens, each with persistent identifiers and direct download links; (ii) pathogen-specific evaluation metrics that submissions must report, allowing direct head-to-head comparison only on the same dataset; and (iii) a credibility framework combining mandatory dataset attestation, ORCID-linked attribution, public peer comments, and administrator verification. As a case study, four published Mycobacterium tuberculosis drug-resistance pipelines were evaluated against the WHO TB mutation catalogue, demonstrating the framework’s discriminating power. PathoBench is open for community contributions across all ten supported pathogens. Availability and implementation PathoBench is freely available at https://pathobench.vercel.app . Source code is released under the MIT license at https://github.com/BPHL-Molecular/pathobench . The platform requires no installation for end users; programmatic access is available via a Supabase REST API. Contact yibo.dong@flhealth.gov Supplementary information Supplementary data are available at Bioinformatics online.

Objective Magnetic resonance imaging (MRI)‐visible enlarged perivascular spaces (PVS) are markers of cerebral small vessel disease (SVD) and aging, processes implicated in both neurodegenerative and cerebrovascular pathologies. However, longitudinal positron emission tomography (PET) studies examining PVS as a mechanism underlying Alzheimer's disease (AD) pathophysiological progression are lacking. Our overall objective was to investigate the associations of baseline PVS burden with white matter hyperintensity (WMH) volume, amyloid‐PET, and tau‐PET, both cross‐sectionally and longitudinally. Methods We examined 2,229 participants across the aging‐AD spectrum from the Mayo Clinic Study of Aging (MCSA) and the Mayo Alzheimer's Disease Research Center (ADRC) (mean age = 68.59 ± 12.70 and 48.94% women). PVS and WMH were quantified using a novel in‐house algorithm. Amyloid on [ 11 C]Pittsburgh Compound B (PiB)‐PET and tau on AV1451‐PET were measured. Cross‐sectional regional and global associations were examined using canonical correlation analysis (CCA). Longitudinal associations were examined using age‐ and sex‐adjusted linear mixed effect (LME) models with natural splines and subject‐wise 10‐fold cross‐validation. Result Three distinct associations were observed: (1) PVS in the basal ganglia (PVS‐BG) was associated with greater WMH volume both cross‐sectionally and longitudinally; (2) PVS‐BG covaried with higher PiB standardized uptake value ratio (SUVR) cross‐sectionally, with longitudinal trajectory associations limited to amyloid‐negative individuals; (3) PVS in the centrum semiovale (PVS‐CSO) was not associated with amyloid or tau, but was associated with occipital WMH, a pattern characteristic of CAA. Interpretation Findings lend support for PVS‐BG as an early indicator of small vessel dysfunction and WMH pathogenesis. Individuals with higher PVS‐BG burden exhibited higher WMH burden and faster WMH progression, suggesting that PVS‐BG may identify individuals at increased risk of progressive SVD. Evidence linking PVS to downstream AD biomarker progression was weaker. Findings support the relevance of PVS‐CSO to CAA, suggesting that they may reflect changes occurring early in the disease process. ANN NEUROL 2026