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Simple Summary: Incidence of brain metastases from genito-urinary cancers has increased over the last years due to improved imaging techniques and better survival outcomes for patients even at an advanced metastatic stage thanks to therapeutic advances. However, no clear consensus exists on their management, and every case ought to be discussed in a multidisciplinary panel. We perform a single-centre retrospective study to report on incidence, patient demographics, clinicopathological characteristics, and treatment modalities. We also manage to identify predictive factors of outcome. Background: Incidence of brain metastases is precisely unknown and there is no clear consensus on their management. We aimed to determine the incidence of brain metastases among patients with genito-urinary primaries, present patients' characteristics and identify prognostic factors. Method: We identified 51 patients treated in Geneva University Hospitals between January 1992 and December 2019. We retrospectively correlated their overall survival with 23 variables. We repeated a multivariate analysis with significant variables. Results: Overall incidence of Brain Metastases (BMs) among Genito-Urinary (GU) patients is estimated to be 1.76% (range per primary GU tumour type: 0.00–6.65%). BMs originate from germ cell tumours in two cases (3.92%), from urothelial cell carcinoma in 15 cases (29.41%), from prostate cancer in 13 cases (25.49%), and from renal cell carcinoma in 21 cases (41.18%); there are no BMs from penile cancer in our cohort. The median age at BM diagnosis is 67 years old (range: 25–92). Most patients (54%) have a stage IV disease at initial diagnosis and 11 patients (22%) have BM at initial diagnosis. Only six patients (12%) are asymptomatic at BM diagnosis. The median Overall Survival (OS) from BM diagnosis is 3 months (range: 0–127). Five patients (10%) are long survivors (OS > 24 months). OS is significantly influenced by patient performance status and administration of systemic treatment. In the absence of meningeal carcinomatosis, OS is influenced by systemic treatment and stereotactic radiosurgery. We also apply the Graded Prognostic Assessment (GPA) score to our cohort and note significant differences between groups. Conclusion: Brain metastases from solid tumours is not a uniform disease, with a prognosis varying a lot among patients. The optimal management for patients with genito-urinary malignancies with brain metastases remain unclear and further research is needed. [ABSTRACT FROM AUTHOR]

Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, characterized by a high degree of intertumoral heterogeneity. However, a common feature of the GBM microenvironment is hypoxia, which can promote radio- and chemotherapy resistance, immunosuppression, angiogenesis, and stemness. We experimentally defined common GBM adaptations to physiologically relevant oxygen gradients, and we assessed their modulation by the metabolic drug metformin. We directly exposed human GBM cell lines to hypoxia (1% O2) and to physioxia (5% O2). We then performed transcriptional profiling and compared our in vitro findings to predicted hypoxic areas in vivo using in silico analyses. We observed a heterogenous hypoxia response, but also a common gene signature that was induced by a physiologically relevant change in oxygenation from 5% O2 to 1% O2. In silico analyses showed that this hypoxia signature was highly correlated with a perinecrotic localization in GBM tumors, expression of certain glycolytic and immune-related genes, and poor prognosis of GBM patients. Metformin treatment of GBM cell lines under hypoxia and physioxia reduced viable cell number, oxygen consumption rate, and partially reversed the hypoxia gene signature, supporting further exploration of targeting tumor metabolism as a treatment component for hypoxic GBM. [ABSTRACT FROM AUTHOR]