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Abstract Background Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma. Methods/design GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland. Trial registration NCT05664464. Registered 23 December 2022.

Objectives: The proliferative activity of the Ki-67 index is important in decision-making of adjuvant treatments in early breast cancer. Its reliability can be reduced by inter-observer variability. This analysis’ objective is to evaluate the robustness of Ki-67 values within one center over 5 years and to compare its distribution with a published dataset. Materials and methods: Ki-67 indices of early breast cancers treated at St. Gallen Breast Center were collected (2010–2014; 1154 patients). Distribution of Ki-67 values was analyzed for each year, along with histologic subtype and grading. Tumors were classified into intrinsic subtypes using two definitions: 2013 St. Gallen Consensus and the refined definition by Maisonneuve (“Milano Group”). Our institution’s Ki-67 cut-off value was adjusted to obtain the same distribution of luminal subtypes as published data of the Milano Group. Results: Ki-67 index frequency distributions were comparable between years (mean 26–30%, median 22–26%). Shape and position of the distribution curves were nearly identical. Ki-67 values correlated with tumor grade (median Ki-67: G1: 12.0%, G2: 21%, G3: 38%). Standard deviation of Ki-67 increased with higher grading (G1: 6.9; G2: 9.2; G3: 18.2; p