Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.
Advances in molecular profiling and the application of advanced imaging techniques are currently refreshing diagnostic considerations in meningioma patients. Not only technical refinements but also sophisticated histopathological and molecular studies have the potential to overcome some of the challenges during meningioma management. Exact tumor delineation, assessment of tumor growth, and pathophysiological parameters were recently addressed by "advanced" MRI and PET. In the field of neuropathology, high-throughput sequencing and DNA methylation analysis of meningioma tissue has greatly advanced the knowledge of molecular aberrations in meningioma patients. These techniques allow for more reliable prediction of the biological behavior and clinical course of meningiomas and subsequently have the potential to guide individualized meningioma therapy. However, higher costs and longer duration of full molecular work-up compared with histological assessment may delay the implementation into clinical routine.This review highlights the diagnostic challenges of meningiomas from both the neuroimaging as well as the neuropathological side and presents the latest scientific achievements and studies potentially helping in overcoming these challenges. It complements the recently proposed European Association of Neuro-Oncology guidelines on treatment and diagnosis of meningiomas by integrating data on nonstandard imaging and molecular assessments most likely impacting the future.
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