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Diffuse gliomas continue to be an important problem in neuro-oncology. To solve it, studies have considered the issues of molecular pathogenesis from the intratumoral heterogeneity point. Here, we carried out a comparative dynamic analysis of the different cell populations' content in diffuse gliomas of different molecular profiles and grades, considering the cell populations' functional properties and the relationship with patient survival, using flow cytometry, immunofluorescence, multiparametric fluorescent in situ hybridization, polymerase chain reaction, and cultural methods. It was shown that an increase in the IDH-mutant astrocytomas and oligodendrogliomas malignancy is accompanied by an increase in stem cells' proportion and mesenchymal cell populations' appearance arising from oligodendrocyte-progenitor-like cells with cell plasticity and cells' hypoxia response programs' activation. In glioblastomas, malignancy increase is accompanied by an increase in both stem and definitive cells with mesenchymal differentiation, while proneuronal glioma stem cells are the most likely the source of mesenchymal glioma stem cells, which, in hypoxic conditions, further give rise to mesenchymal-like cells. Clinical confirmation was a mesenchymal-like cell and mesenchymal glioma stem cell number, and the hypoxic and plastic molecular programs' activation degree had a significant effect on relapse-free and overall survival. In general, we built a multi-vector model of diffuse gliomas' pathogenetic tracing up to the practical plane.
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INTRODUCTION: Preoperative stereotactic radiosurgery (pre-SRS) is a recent advancement in the strategy for brain metastasis (BM) management, and available data demonstrate the advantages of pre-SRS before postoperative radiation treatment, including lower rates of local toxicity, leptomeningeal progression, and a high percentage of local control. The authors presented the results of pre-SRS in patients with BM. MATERIALS AND METHODS: Nineteen patients with BM (11 female and eight male) have been treated at N.N. Burdenko Medical Research Center for Neurosurgery (Moscow, Russia) and Gamma-Knife Center (Moscow, Russia) using pre-SRS. A total of 22 symptomatic metastatic lesions were preoperatively irradiated in the series. Eight patients had multiple BM (number of metastases ranged between two and seven). The median target volume for combined treatment was 14.131 cc (volumes varied between 2.995 and 57.098 cc; mean - 19.986 cc). The median of the mean target dose was 18 Gy, ranging between 12.58 and 24.36 Gy. Results: All patients tolerated pre-SRS well, without any neurological deterioration, and surgical treatment was performed as scheduled. The median follow-up period was 6.3 months (ranging between five weeks and 22.9 months). In 17 out of 19 patients, follow-up magnetic resonance (MR) images obtained two or three months after the combined treatment demonstrated the postoperative cavity without any signs of postradiation alterations in the perifocal tissues. In two observations, peritumoral edema was present. Local recurrences were found in two cases, 5.5 and 17.4 months after treatment. Radionecrosis was present in one observation after 4.6 months of follow-up. Two patients died of disease progression and are presented as illustrative cases. CONCLUSION: The combined treatment of secondary brain tumors has proved to be the best treatment option. Preoperative stereotactic radiosurgery may decrease radiation-induced toxicity and rates of local tumor progression. The potential hazards of pre-SRS associated with the postoperative healing of irradiated soft tissues of the head were not confirmed in our study. The decision of pre-SRS should be made by the tumor board, including specialists in neurosurgery, neuro-oncology, and radiation oncology, if the diagnosis of BM is based on oncological history and visualization data.
