Background and purpose:Stereotactic radiotherapy (SRT) is a standard approach for treating multiple brain metastases. However, variation in planning practices may impact treatment quality. This study assessed planning consistency and dose-volume-based outcomes across radiation oncology centers. Materials and methods:A Computed Tomography (CT) scan of an anthropomorphic phantom with structure set was distributed to participating centers. Each center created SRT plans as for a clinical case. Dose distributions were evaluated based on Planning Target Volume (PTV) coverage (V100% (PTV)), dose to 95% of Gross Target Volume (GTV) volume (D95% (GTV)), maximal PTV dose (Dmax), conformity index (CI), gradient index (GI), brain volume receiving different percentages of the prescribed dose, and doses delivered to 0.035 cm3 and 0.5 cm3 of the brainstem. Results:Twenty-four centers, using 30 treatment units, submitted plans. The V100% (PTV) ranged from 95% to 100%, with Dmax between 110% and 150% of the prescribed dose. Mean GTV dose ranged from 110% to 135%, and 81% of GTVs had D95% between 110% and 120%. High conformity was achieved in 74% of plans (CI < 1.1), while 67% had a GI between 3.4 and 5. All plans met clinical dose constraints for the brainstem and uninvolved brain. Conclusion:This interinstitutional comparison demonstrated high plan quality and adherence to critical organ constraints, despite variability in planning strategies. These findings support nationwide planning and quality assurance standards to ensure consistently high-quality SRT.
Patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) face a high risk of disease progression. While radical cystectomy (RC) remains the recommended standard of care, many patients are unfit for or unwilling to undergo radical surgery, leading to bladder-sparing strategies spreading in real-world practice. This study aims to describe the oncological outcomes of patients diagnosed with BCG-unresponsive NMIBC treated with gemcitabine/docetaxel (Gem/Doce), electromotive drug administration of mitomycin C (EMDA/MMC), further BCG, or upfront RC. We included patients diagnosed with BCG-unresponsive NMIBC treated across 21 European centers (2009–2024) with either intravesical Gem/Doce, EMDA/MMC, further BCG, or upfront RC. Cumulative incidence curves were used to estimate the risk of recurrence, high-grade recurrence, progression, cancer-specific and overall mortality. Multivariable Cox regression models were used to assess the association between treatment type and the risk of recurrence and progression. Of the 361 patients, 104 (28
SARS-CoV-2 evolution has reduced the efficacy of clinical monoclonal antibodies, underscoring the need for therapeutics targeting conserved viral regions. The Spike (S) heptad repeat 2 (HR2) stem helix is highly conserved across SARS-CoV-2 variants and related betacoronaviruses. Although antibodies to this region can neutralize infection, their natural occurrence and evolution remain poorly understood. We previously identified human neutralizing antibodies to a conserved peptide within this region (HR2 coldspot). Here, we show that plasma IgG reactivity to this region remains rare, even after repeated antigen exposure. Longitudinal analysis over 30 months revealed continued somatic hypermutation of HR2-specific antibodies, yet none surpassed the potency or breadth of hr2.016, which emerged shortly after primary infection. Crystal structures of four HR2 stem helix antibodies revealed convergent recognition across distinct antibody lineages. Comparison of hr2.016 with its non-neutralizing clonal relative hr2.086 showed that structural convergence masks distinct binding kinetics. Surface plasmon resonance and molecular dynamics simulations revealed a more stable interaction network for hr2.016, with slower dissociation and prolonged S residence time. Neutralization required the IgG format, supporting an avidity-driven mechanism. Together, these findings define kinetic and avidity constraints governing neutralization at the HR2 stem helix and position hr2.016 as a resilient therapeutic candidate.
Onset of the symptoms in patients with ulcerative colitis and Crohn's disease is some- times characterized by osteoarticular manifestations. The usual presentation of periph- eral arthritis is asymmetric, polyarticular and migrant, often involving large joints of the upper and lower limbs, unlike rheumatoid arthritis. This study analyses the statistical incidence of arthritic manifestations in elderly patients with inflammatory bowel disease.
