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Background Glioblastoma (GBM) is the most aggressive and among the most common primary brain malignancies in adults. The current standard of care for primary GBM consists of maximal surgical resection, followed by radiation therapy with concurrent temozolomide (TMZ) for six weeks and six subsequent cycles of adjuvant TMZ. The prognosis remains poor with a median overall survival of 14.6 months. The mean age at diagnosis is 62 years. This study aimed to analyse the demographics and clinicopathological features of a cohort of patients by reviewing their electronic medical records. Furthermore, we investigated if known prognostic factors described in literature had a significant influence on the survival time of the patients in this cohort. Methods We reviewed the electronic medical records of 53 patients with primary or secondary GBM who underwent multiple resections over the past 20 years at the University Hospitals Leuven. 36 primary GBM patients were included for statistical analysis. Results The median OS of the primary GBM patients, with a mean age of 55 years, was 22 months. Primary GBM patients who had a postoperative treatment with 6 adjuvant TMZ cycles survived significantly longer than patients with less than 6 adjuvant TMZ cycles (p=0.0324) or no adjuvant TMZ therapy (p=0.0162). Other known prognostic features, including EOR, age at diagnosis and clinical performance status had no significant prognostic value in this cohort. Conclusion Based on the results of this study, primary GBM patients with multiple resections are younger patients with a remarkably longer median OS compared to the findings in literature. Median OS is significantly longer in patients who receive 6 adjuvant TMZ cycles as postoperative treatment.

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Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. It remains to be a largely incurable disease with devastating outcomes, indicated by its 5-year survival rate of a dismal 7%. Additionally, no tangible changes have been made in the treatment of GBM since the Stupp protocol was published in 2005, despite many studies showing promising preclinical results. Preclinical research still largely depends on in vitro models that poorly represent the disease. This can be attributed to a lack of three-dimensional cues and to the fact that most of these models lack influences of the microenvironment of the tumor. In vivo models on the other hand can better recapitulate the genomic and transcriptomic profiles of tumors but are notoriously expensive and demanding. The creation of clinically relevant models that retain the complexity of the disease, remain high-throughput and are amenable to detailed analysis will allow us to better understand and therapeutically manipulate complex tumors such as GBM. Hydrogels, a scaffold-based cell culture platform, gain in popularity because of their biocompatibility and chemical flexibility for modeling the extracellular matrix (ECM). They allow for a consensus between the physiological relevance of in vivo and the cost-effectiveness and throughput of simplified two-dimensional (2D) in vitro models. To model the brain ECM, we make use of glycosaminoglycan-based hydrogels which represent fundamental building blocks of the GBM microenvironment. We employ patient-derived cell lines (PDCLs) as they enable a more accurate image of the complex molecular landscape of GBM. We show the biocompatibility of this platform with our PDCLs and their shift towards a more mesenchymal subtype upon encapsulation in the hydrogel scaffold, which is also retained over time. Additionally, we illustrate that although hydrogels present a promising novel and highly biologically relevant cell culture model, their implementation into routine preclinical practice presents several challenges. We show their discordance with standard biochemical assays and sample processing methods indicating a need for specialized protocols and equipment. Nonetheless, hydrogels are useful for selectively mimicking certain biological processes with incredible tunability as indicated by our addition of macrophages into a co-culture system within the brain ECM. We were able to reliably distinguish both cell types in this system and draw conclusions on their spatial localization and polarization stage using multiplex immunohistochemistry. The transition towards three-dimensional (3D) culture methods has proven to have the potential to completely change the way preclinical platforms are used. A paradigm shift is currently underway, expediting the technological advances needed to overcome the limitations that are still present. Nevertheless, the future of 3D culturing is bright, and the first major successes are imminent.