Wolfgang Wick

Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard of care for newly diagnosed GB involves surgical resection followed by radiochemotherapy with temozolomide, with or without tumor‐treating fields. In recent years, various efforts have been made to identify suitable molecularly targeted treatment options for malignant brain tumors. This meta‐analysis provides an overview of recently published randomized controlled trials (RCTs) with and without molecular stratification, analyzing targeted agents in patients with newly diagnosed GB. The Cochrane Library, MEDLINE (Ovid), ClinicalTrials.gov , WHO's International Clinical Trials Registry Platform, and Google Scholar were searched for RCTs on targeted therapies in patients with newly diagnosed glioblastoma. Hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS) were extracted and pooled in a random‐effects meta‐analysis. Twelve RCTs (n = 3941 patients) involving protein kinase inhibitors, proteasome and histone deacetylase inhibitors, anti‐angiogenic approaches and poly (ADP‐ribose) polymerase (PARP) inhibitors were included in the meta‐analysis. None of the targeted agents achieved a significant benefit with regard to OS (HR = 0.98 [95% confidence interval (CI) 0.86‐1.11, P = .7731]). By comparison, targeted therapy showed a benefit for PFS (HR = 0.83 [95% CI 0.74‐0.94, P = .0037]), especially for patients with an unmethylated O6‐methylguanine‐DNA‐methyltransferase (MGMT) promoter (0.75 [95% CI 0.56‐0.99, P = .0440]). Prolongation of PFS was largely driven by VEGF inhibition with bevacizumab (HR = 0.70 [95% CI 0.61‐0.80, P = .0000]). VEGF inhibition with bevacizumab prolonged PFS in patients with newly diagnosed glioblastoma compared to standard care. However, no improvement in OS was observed with any of the targeted agents.

Background and purpose Population‐based studies suggest severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines may trigger neurological autoimmunity including immune‐mediated thrombotic thrombocytopenia. Long‐term characterization of cases is warranted to facilitate patient care and inform vaccine‐hesitant individuals. Methods In this single‐center prospective case study with a median follow‐up of 387 days long‐term clinical, laboratory and imaging characteristics of patients with neurological autoimmunity diagnosed in temporal association (≤6 weeks) with SARS‐CoV‐2 vaccinations are reported. Results Follow‐up data were available for 20 cases (central nervous system demyelinating diseases n = 8, inflammatory peripheral neuropathies n = 4, vaccine‐induced immune thrombotic thrombocytopenia n = 3, myositis n = 2, myasthenia n = 1, limbic encephalitis n = 1, giant cell arteritis n = 1). Following therapy, the overall disability level improved (median modified Rankin Scale at diagnosis 3 vs. 1 at follow‐up). The condition of two patients worsened despite immunosuppressants possibly related to their autoimmune diagnoses (limbic encephalitis n = 1, giant cell arteritis n = 1). At 12 months’ follow‐up, 12 patients achieved complete clinical remissions with partial responses in five and stable disease in one case. Correspondingly, autoimmune antibodies were non‐detectable or titers had significantly lowered in all, and repeat imaging revealed radiological responses in most cases. Under vigilant monitoring 15 patients from our cohort underwent additional SARS‐CoV‐2 vaccinations (BNT162b2 n = 12, mRNA‐1273 n = 3). Most patients ( n = 11) received different vaccines than prior to diagnosis of neurological autoimmunity. Except for one short‐lasting relapse, which responded well to steroids, re‐vaccinations were well tolerated. Conclusions In this study long‐term characteristics of neurological autoimmunity encountered after SARS‐CoV‐2 vaccinations are defined. Outcome was favorable in most cases. Re‐vaccinations were well tolerated and should be considered on an individual risk/benefit analysis.