CNS Oncology最新文献

Aim: Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. Methodology: A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an in vitro model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. Results: We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Conclusion: Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of in vitro cancer models, possibly also suitable for other cell systems.

Atypical teratoid/rhabdoid tumor (ATRT) is a malignant CNS embryonal tumor that mostly occurs in childhood, adult cases are rare. We report a case of a 23-year-old male with an extra-axial dura-based lesion in the left frontal area, previously diagnosed as gliosarcoma. After 6 years, the patient had a recurrence and the previous slides were reviewed. Tumor was positive for vimentin and negative for INI1. The differential diagnosis for this extra-axial tumor with long survival was rhabdoid meningioma with INI1 loss or ATRT. DNA methylation profiling was performed to reach the final and the most definitive diagnosis; the result was ATRT. Our case suggests the usefulness of DNA methylation profiling for diagnosing challenging CNS tumors.

Aim: To explore fecal short-chain fatty acids and neurotransmitter alterations in a mouse-glioma model and glioma patients. Methods: Liquid chromatography-mass spectrometry and 16S rRNA-sequencing from fecal samples were performed to measure metabolite levels and taxa abundance in mice/humans. Mice underwent GL261 implantation with/without temozolomide. Glioma patients were compared with healthy controls. Results: Glioma altered several short-chain fatty acids and neurotransmitter levels. Reduced 5-hydroxyindoleaceic acid and norepinephrine levels were seen in mice and humans. Interestingly, temozolomide treatment abrogates the effects of glioma on fecal metabolites. Conclusion: Our findings demonstrate the interplay between glioma and the gut-brain axis. Further work is required to identify pathways within the gut-brain axis by which glioma influences and promotes the modulation of fecal metabolites and microbiome.

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.

Aim: To determine if enrollment on glioblastoma (GBM) interventional clinical trials (ICTs) in the USA is representative of the population. Materials & methods: We queried ClinicalTrials.gov for all ICTs in GBM from 1994 to 2019. Demographics were obtained from ClinicalTrials.gov or the trial publication and compared with population data from Central Brain Tumor Registry of the United States. Results: In total, 10617 GBM patients were enrolled in 118 adult ICTs: median age was 54.0 (10.05 years younger than Central Brain Tumor Registry of the United States). Age was most discrepant in recurrent tumors, nonrandomized trials and consortium studies. Median age improved from 52.0 to 59.5 over 25 years. Women represented 37.5% of subjects. Conclusion: GBM ICTs under-represent older patients but representation of women reflects the population. ICTs need to be designed to better represent the population.

The standard regimen for the treatment of newly diagnosed primary CNS lymphoma (PCNSL) remains regimens that contain high-dose methotrexate (MTX). While these regimens can provide control for some patients, there is a dearth of options for the treatment of patients with PCNSL who cannot tolerate MTX-containing regimens, or whose cancers are refractory to MTX. In this article, we review a promising new option; ibrutinib, a Bruton tyrosine kinase inhibitor, for patients with relapsed and refractory PCNSL.

Endolymphatic sac tumors (ELSTs) are rare, locally invasive, vascular tumors of the temporal bone. These lesions are associated with von Hippel-Lindau syndrome but may arise sporadically. Early surgical intervention is recommended to prevent permanent neurologic deficits; however, many ELSTs are unresectable or are subtotally resected due to neurovascular compromise. Chemotherapeutic salvage therapy in trials of neoplasms of associated syndromes has targeted angiogenesis with variable response. We present the case of a sporadic ELST, previously minimally responsive to bevacizumab, treated with pazopanib, a multi-kinase inhibitor and antiangiogenic, with good response. Cases such as our patient may demonstrate the utility of novel antiangiogenics in the treatment of these rare neoplasms, particularly when the tumor is unresectable or necessitates subtotal resection.

Aim: Therapeutic targeting of BRAF alterations in primary brain tumor patients has demonstrated clinical activity in case reports and early trials; however, there is limited high-level evidence of the efficacy. Patients & results: Targeting BRAF V600E mutations with concurrent dabrafenib and trametinib in anaplastic pleomorphic xanthoastrocytoma resulted in a transient radiographic and clinical response and no therapeutic benefit in a patient with an epithelioid glioblastoma. Conclusion:BRAF/MEK inhibition did not produce a durable treatment effect in glioblastoma or pleomorphic xanthoastrocytoma with BRAF V600E alterations. Heterogenicity of related cases in the literature makes an evaluation of efficacy BRAF targeting therapies in gliomas difficult and requires additional investigation.