This study describes and evaluates the acceptance procedure for a ViewRay (VR) MRIdian 0.35T MR-Linac, emphasizing key challenges, limitations, and recommendations to enhance clinical performance and accuracy.

A comprehensive acceptance test was conducted at a single institution, following the manufacturer's protocols and aligned with established acceptance guidelines. Specific tools and phantoms were used to assess three primary components: mechanical, dosimetric, and Magnetic Resonance Imaging (MRI).

Overall, the test outcomes satisfied the manufacturer's specifications. However, certain issues were identified: high couch attenuation at specific gantry angles (leading to their exclusion from treatment), variations in magnetic field homogeneity at different gantry angles, and discrepancies between TPS calculations and measurements for field output factors smaller than 0.83 cm × 0.83 cm.

This work provides a detailed account of the acceptance testing procedure and establishes a QA baseline for 0.35T MR-Linac systems. In doing so, it also identifies key system limitations, such as couch attenuation, magnetic field inhomogeneity, and small-field output discrepancies, underscoring the need for careful gantry angle selection, field homogeneity optimization, and meticulous validation of very small fields.

Heart failure remains one of the leading causes of cardiovascular morbidity and mortality, impairing the quality of life. Based on randomized, controlled clinical trials, SGLT2 inhibitors significantly improve outcomes and reduce symptoms. However, real-world evidence is essential to better assess their effectiveness and safety in everyday clinical practice.

To evaluate the effects of empagliflozin therapy on the quality of life and functional status, as well as to assess its safety profile in the Hungarian cohort of the international Emp-Activity study, covering the full spectrum of heart failure.

This prospective, non-interventional, multicenter, observational study involved symptomatic heart failure patients enrolled from 11 Hungarian centers. A total of 106 patients were enrolled, of whom 101 were assigned to the empagliflozin cohort and 5 to the non-empagliflozin cohort. Patients received empagliflozin as part of routine heart failure therapy and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at baseline and after 24 weeks. Functional status was assessed using the New York Heart Association (NYHA) classification.

101 patients were enrolled to the empagliflozin cohort (median age 69 years, 28.7% female), primarily in NYHA class II and III. Among them, 57% had HFrEF, 19% HFmrEF, and 22% HFpEF. The most frequent etiology was ischemic heart disease (42%). The most common comorbidities included hypertension (58%), atrial fibrillation (33%), diabetes mellitus (26%), and hyperlipidemia (25%). A significant improvement was observed in the KCCQ-12 overall score (74.3 ± 19.5 vs. 67.1 ± 19.5, p<0.01), with clinically meaningful improvement (≥5-point increment) in 53% of patients. The NYHA class improved significantly. Systolic blood pressure decreased (131 ± 16 mmHg vs. 127 ± 17 mmHg, p = 0.02), while diastolic blood pressure, serum creatinine, and potassium levels remained stable during the 24-week follow-up.

In Hungarian patients with heart failure, 24-week empagliflozin treatment resulted in significant improvements in the quality of life and functional capacity, while being well tolerated. These findings support the effectiveness and safety of empagliflozin in routine clinical practice across the full spectrum of heart failure. Orv Hetil. 2026; 167(7): 257-264.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistent nephroprotective effects across diverse patient populations, including those with glomerular disease without diabetes mellitus. These somehow unexpected benefits cannot be solely explained by glycosuria and intrarenal hemodynamic effects. Experimental evidence largely supports the effects of SGLT2 inhibitors on several pathways, many of them outside the kidneys. This review explores the mechanisms underlying these benefits, focusing on those of importance in primary and secondary glomerulonephritis. In addition to glucose homeostasis, SGLT2 inhibitors exert local and systemic effects that mimic nutrient deprivation, impacting inflammation, immunity, autophagy, hypoxia responses, ferroptosis, lipotoxicity, and energy metabolism. Sodium-glucose cotransporter 2 inhibitors modulate inflammatory pathways through suppression of cytokines and NLR family pyrin domain containing 3 inflammasome activity, mechanisms relevant to immunoglobulin A glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody-associated vasculitis. They also influence immune cell metabolism, inhibit T-cell activation, and potentially modulate B-cell and macrophage polarization. There is evidence that autophagy may show a dual role in glomerular disease. It could activate innate and adaptive immunity, so triggering the disease, or may protect podocytes, so reducing proteinuria and the risk of progression. Sodium-glucose cotransporter 2 inhibition also modulates the hypoxia inducible factor axis and reduces ferroptosis, possibly contributing to attenuate hypoxia-induced kidney damage. The upregulation of ketogenesis and activation of nutrient-sensing pathways (adenosine monophosphate-activated protein kinase-activated protein kinase, sirtuins, and mammalian target of rapamycin) further supports their role in metabolic reprogramming. Finally, they contribute to preserve gerosuppressor functions by increasing kidney Klotho, a protein with anti-aging, and-inflammatory, and antifibrotic effects, and liver betaine. Although direct clinical evidence on the specific molecular pathways targeted by SGLT2 inhibitors in glomerulonephritis remains limited, preclinical data and emerging human observations suggest SGLT2 inhibitors may offer therapeutic advantages beyond non-specific kidney-cardiovascular protection.

Identify factors influencing audiological care for chemotherapy-induced ototoxicity from the perspectives of oncology providers in the Veterans Health Administration (VA), and quantify audiology service use among Veterans receiving ototoxic chemotherapies.

We surveyed VA oncology providers to identify barriers and facilitators to ototoxicity management (OtoM). We also conducted a VA-wide retrospective cohort analysis over a 5-year period to quantify audiology service use among Veterans who received cisplatin, carboplatin, or oxaliplatin chemotherapy.

A total of 30,643 Veterans received platinum-based chemotherapy from 2014 to 2019. Few of them (< 10% on cisplatin, < 5% on carboplatin or oxaliplatin) accessed audiology services within a year of treatment. Of the 8702 patients on cisplatin, only 9.6% had two or more audiology encounters. Thirty-six oncology providers completed our survey. Most providers believed OtoM should be routine for patients on cisplatin (97%) or carboplatin (70%), but they overestimated audiology service provision levels relative to our analysis. Most providers would consider giving a different chemotherapy drug (73%) or decrease the dose (56%) for patients with ototoxicity, yet only 36% routinely referred patients to audiology. Access, perceived need, and resources were major barriers to OtoM, while care coordination was a primary facilitator.

OtoM is a care-gap for Veterans with cancer, despite its perceived value to VA oncology providers. Cisplatin and carboplatin frequently add hearing loss and tinnitus to survivors' treatment burdens. This study offers insights into oncology providers' views on OtoM, guiding efforts to address the identified care gap.

To analyze the correlation between lipid levels and the severity of polycystic ovary syndrome (PCOS) and its predictive value for pregnancy outcome.

This retrospective study included 275 PCOS patients treated with ovulation induction therapy and 234 healthy controls (used only for baseline comparisons). Lipid levels were correlated with disease phenotype and sex hormones using Spearman/Pearson coefficients. Binary logistic regression and ROC curves assessed the predictive value of lipid levels for pregnancy failure.

There were statistically significant differences between the two groups in glycemic indexes (fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR)) and sex hormone indexes (testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), anti-Müllerian hormone (AMH)). The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) were significantly elevated in patients with PCOS and were closely correlated with the severity of the disease. In addition, these four lipid parameters were significantly positively correlated with T, LH, FSH, and AMH, and significantly negatively correlated with E2. Elevated levels of T, LH, TG, LDL-C, and Apo B were independent risk factors for pregnancy failure after ovulation induction treatment. TG assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.861 (sensitivity 75.61%, specificity 85.53%); LDL-C assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.868 (sensitivity 75.61%, specificity 83.55%); and Apo B assisted in predicting pregnancy failure after ovulation induction therapy in PCOS patients with an AUC of 0.836 (sensitivity 74.80%, specificity 86.84%).

Lipid levels were significantly correlated with the severity of disease in PCOS patients, and TG, LDL-C, and Apo B levels assisted in predicting the occurrence of pregnancy failure after ovulation induction therapy.

Although prostate magnetic resonance imaging (MRI) enhances the detection of high-grade prostate cancer (PCa), its predictive role in active surveillance (AS) of favorable risk PCa is unclear. We examined the association between baseline MRI Prostate Imaging-Reporting and Data System (PI-RADS) score and Gleason Grade Group (GG) upgrade risk among patients managed with AS.

We systematically searched eight databases to identify studies evaluating the association between baseline PI-RADS score and the risk of GG upgrade in patients managed with AS for PCa (PROSPERO: CRD42024567762). We pooled the hazard ratios (HR)using Hartung-Knapp random-effects meta-analysis models. We assessed the risk of bias using the ROBINS-I tool.

We included eleven studies (n = 6309) in the meta-analysis. The risk of bias was moderate, attributed to the retrospective and unblinded design of seven included studies. Among studies reporting baseline PI-RADS, 2,640 patients (52.1%) had PI-RADS 1-3 lesions, and 2,421 patients (47.9%) had PI-RADS 4-5 lesions. Baseline PI-RADS 4-5 was associated with an increased risk of upgrade compared to those with PI-RADS 1-3 lesions (HR:2.21, 95%CI: 1.66-2.93, p<.001). Compared to PI-RADS 1-2, the presence of PI-RADS 3 (HR:1.88, 95%CI: 1.29-2.74, p=.008), PI-RADS 4 (HR:2.73, 95%CI: 2.08-3.58, p<.001), or PI-RADS 5 (HR:3.69, 95%CI: 2.50-5.45, p<.001) lesions were associated with an increased risk of upgrade.

Baseline prostate MRI finding as assessed with PI-RADS is highly prognostic for GG upgrading among patients with favorable risk PCa managed with AS. These findings support further study of tailored surveillance strategies based on initial MRI findings.

Project Optimus has been reforming the dose selection and optimization paradigm in oncology. In this context, model-informed drug development (MIDD) approaches were utilized to validate the optimal dose selection of 6 mg/kg every 3 weeks (Q3W) for datopotamab deruxtecan (Dato-DXd) in patients with HR-positive/HER2-negative breast cancer (HR+/HER2- BC). A Tumor Growth Inhibition (TGI)-Progression-Free Survival (PFS) modeling framework was developed to assess the relationship between Dato-DXd PK exposure, tumor dynamics, and PFS, and support virtual trial simulations at different Dato-DXd dose levels. Simulations suggested that Dato-DXd at 6 mg/kg Q3W provide superior tumor control and improved PFS compared to a lower dose in patients with HR+/HER2- BC. This work underscores the importance of integrating advanced modeling techniques into the dose optimization paradigm.

Merging two radiation oncology information systems (ROISs) is often necessary due to system changes or hospital integrations. ROIS integration is a high-risk procedure, that requires clear procedural guidelines and comprehensive QA methods to ensure safe practice.

This paper presents checklists, procedures, and challenges associated with integrating a ROIS into a centralized system, providing procedural guidelines and QA methods. It also shares our experience of merging with one ROIS into another.

The integration process comprised five major components: machine information; under-treatment patients' information (treatment plans, history, images, and electronic medical records [EMR]); user-generated workflows; ROIS user information; and beam-related information, if any (e.g., beam calibration). The procedures were divided into three parts: site survey and preparation-phase activities, QA during integration, and QA after integration. Software tools were developed to compare data before and after the merger. Integration of legacy data was not considered in this process.

We successfully integrated a standalone practice site into a main ROIS, which may serve multiple sites, over the course of a single weekend using the developed tools and checklists. By the following Monday, after 45-person hours of integration work by therapists, dosimetrists and physicists, the newly integrated practice site was able to seamlessly use the centralized ROIS to continue radiation treatment for its patients already under care. The entire procedure was completed without any downtime at any site.

We have developed and successfully tested a structured set of checklists, procedures, and tools for the seamless integration of a practice site into an existing ROIS. This approach provides the radiation oncology community with a framework for achieving safe and efficient practice integration.

Little is known about the genetic background of individuals with familial pancreatic cancer (PC). Integrating germline testing into surveillance may uncover previously unrecognized hereditary susceptibility and expand prevention strategies beyond BRCA testing alone. This study evaluated the genetic landscape of high-risk individuals due to familiality (HRI-FHs) enrolled in a national surveillance program.

Five hundred HRI-FHs from seven centers underwent surveillance and germline testing with a 41-gene NGS panel. Pathogenic/likely pathogenic variants (PGVs) and variants of unknown significance (VUS) were identified and correlated with clinical and imaging findings.

Overall, forty-four (8.8%) out of 500 HRI-FHs carried at least one PGV, including 3.4% in high-penetrance genes (ATM, BRCA1/2, PALB2, BRIP1). Notably, 8 out of 17 (47%) of ATM, BRCA1/2, PALB2 carriers would not have met the national testing criteria based solely on their family history. An additional 5.4% (27/500) carried PGVs in genes linked to other hereditary conditions (CFTR, MUTYH, CTRC, SPINK1, APC), and 39.6% harbored at least one VUS. PGV status, age, and female gender were independent predictors of radiological abnormalities. Two PCs were diagnosed, both in mutation-negative individuals.

Integrating germline testing into surveillance redefines the management of familial PC. It uncovers hereditary susceptibility beyond classical criteria and supports cascade testing. PC also arises in mutation-negative HRI. #NCT05724992.

Human papillomavirus (HPV) vaccination effectively reduces the risk of HPV-attributable cancers, including cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers. Concerns for a lower-than-expected vaccine impact, as defined as an increase in the prevalence of precancer by nonvaccine types, compared to that anticipated based on attribution studies, have been raised in the postvaccination era. Three distinct and nonmutually exclusive processes-HPV type replacement, clinical unmasking, and viral unmasking-could be responsible for this apparent increase of nonvaccine types. HPV type replacement, in which nonvaccine types fill a niche left vacant after the elimination of vaccine types, is unlikely to occur due to the remarkable genetic stability of the virus and the lack of natural competition between individual HPV types. However, clinical unmasking, in which the absence of clinical interventions aimed at eliminating cervical disease caused by vaccine types permits uninterrupted progression of nonvaccine types, may occur since HPV coinfections are common. Alternatively, the observed shift could be completely erroneous due to the false discovery of type replacement via viral unmasking, a diagnostic assay artifact. In this chapter, we describe these processes and the mechanisms underlying them.