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Introduction. Epidermal growth factor receptor (EGFR) is a transmembrane protein of the receptor tyrosine kinase family that is activated in various cancers (non-small cell lung cancer, colorectal cancer, head and neck tumors). In glial brain tumors, increased EGFR expression levels are characteristic of the most aggressive subtype, glioblastoma. Frequent structural changes of EGFR in glioblastoma are amplification of the chromosome region where the EGFR gene is located, point mutations, as well as deletion of exons 2–7 of the EGFR gene leading to the formation of EGFRvIII transcript.Aim. To determine structural changes of the EGFR gene (point mutations and amplification of the EGFR gene, EGFRvIII transcript) in tumor samples using different methods and to evaluate their potential clinical significance.Materials and methods. The study included 75 patients with brain gliomas (70 of them glioblastoma) aged 34 to 78 years (mean age 56 years). DNA and RNA isolation was performed from fresh frozen tumor tissue, as well as from peripheral blood leukocytes. EGFR gene mutations were determined by next-generation sequencing (NGS), and β allele frequency (BAF) comparative analysis (normal-tumor) was performed to determine the copy number of chromosome 7 regions. Quantitative polymerase chain reaction was used to confirm the EGFR gene amplification in tumor samples, and reverse transcription-PCR was used to detect EGFRvIII variant.Results. The NGS method revealed 11/70 (16 %) mutations in coding regions of EGFR gene in glioblastoma samples, the EGFR gene amplification was detected in 26/70 (37 %) cases; no structural changes of the EGFR gene were detected in 5 glioma samples (astrocytoma, oligodendroglioma). All cases of EGFR gene amplification detected by NGS were confirmed by quantitative polymerase chain reaction. To search for EGFRvIII transcript, 31 tumor RNA samples were examined, of which EGFR amplification was present in 12 samples. EGFRvIII transcript was detected only in samples with EGFR gene amplification – 4/12 (33 %). To assess the clinical significance of structural gene alterations, the frequency of occurrence in primary and recurrent glioblastoma samples was compared.Conclusion. The NGS method allows to detect both point mutations and amplification of the EGFR gene. The EGFR gene amplification was associated with EGFRvIII mutation in 33 % of cases. No statistically significant differences in the frequency of structural changes in the EGFR gene between primary and relapsed glioblastomas were found.

Introduction. The standard of treatment for patients with single cerebral metastases is surgery and radiosurgery. The use of these methods significantly increases survival rates.Aim. To compare the results of surgical treatment of patients with single and multiple cerebral metastases.Materials and methods. The study included 40 patients with single and multiple cerebral metastases who underwent neurosurgical intervention in the neuro-oncology department of the N.N. Blokhin National Medical Oncology Research Center from 2010 to 2022.Results. All patients are divided into 3 groups. Group A included 15 patients who removed all available cerebral foci (from 2 to 4). Group B included 10 patients with multiple cerebral metastases who underwent removal of one symptomatic metastasis. In group C, 15 patients who underwent removal of a single metastasis. It was noted that the survival of patients after removal of all cerebral metastases is identical to the survival of patients after removal of single metastasis 11.9 and 12.4 months, respectively. And it was significantly higher than the survival of patients who removed not all cerebral metastases 6.2 months (p = 0.03). Also in group A and C, the percentage of local relapses was identical. Improvement in neurological status was noted in all groups, there was only an increase in cognitive-mnestic disorders in group A, where all cerebral foci were removed. However, these disorders were moderate and did not reach the extent of dementia. The work done shows.Conclusion. Surgical removal of all metastases in patients with multiple brain metastases provides a prognosis similar to that of patients undergoing surgery for single metastasis. Removal of symptomatic metastasis in patients with multiple cerebral lesions in most cases leads to a regression of neurological symptoms and makes it possible to continue treatment with a group of patients whose condition was considered incurable. The percentage of local relapses in the removal of multiple cerebral metastases, subject to oncological principles, is the same as in the removal of single metastases.

The article presents a clinical case of atypical teratoid rhabdoid tumor with one of the longest catamnesis described in literature (109 months) and high quality of life. first, a giant tumor of the frontal lobe with advancement into a lateral ventricle was found in a female patient and totally removed. It was histologically diagnosed as primitive neuroectodermal tumor. Combination treatment consisting of radiotherapy, high-dose polychemotherapy and cellular immunotherapy including intrathecal therapy led to 4-year recurrence-free period. Recurrence of the tumor was resected. The period of the 2nd remission was 34 months. Subsequently, multistage metastasis of the tumor through cerebrospinal fluid tracts of the brain and spinal cord was observed. Twice microsurgical treatment with removal of symptomatic metastases in ventricles Iv and III was performed. In repeat morphological examinations, the tumor was verified as atypical teratoid rhabdoid tumor. The presented clinical case shows the role of active surgical tactics in effective long-term combination treatment of this severe pathology.

Introduction. The surgical stage takes an important place in the complex treatment of patients with cerebral metastases of malignant tumors. In general, all efforts during surgical intervention should be aimed at restoring a good functional status, since severe neurological symptoms can deprive patients of the opportunity to continue complex treatment, which will negatively affect overall survival. The most pronounced neurological symptoms are observed in patients with metastases in the motor area. In this article, we tried to substantiate the need for surgery of cerebral metastases in patients with severe motor deficits, evaluate the results of surgical treatment and also to develop optimal surgical removal techniques.The study object – to assess the effectiveness of surgical removal of metastases in the motor cortex by evaluating the dynamics of motor function recovery and regression of paroxysmal symptoms.Materials and methods. An analysis of the surgical treatment of 18 patients with metastases in the motor area was carried out. Tumor localization was verified using magnetic resonance imaging, before surgery, neuronavigation system Brainlab during surgery. Мagnetic resonance tractography made it possible to assess the localization and degree of compression of the fibers of the cortico-spinal tract. Functional monitoring was not performed during the operation. The operations were performed using a ZEISS OPMI PENTERO 800 microscope.Results. Recovery of motor function after surgery was noted in 17 (94.5 %) cases. It was complete or partial. With metastases of a solid, solid-necrotic, solid-cystic structure, regression of pyramidal symptoms developed gradually, starting from 4 days after surgery. As a rule, rehabilitation therapy (therapeutic exercise, massage, electromyostimulation) is carried out on patients from 3 days after surgery, which accelerated the recovery process. The maximum effect developed on the 15th day after the operation. Faster recovery of motor function was observed in patients with large cystic metastases who underwent surgery in the volume of Ommaya reservoir implantation. They began to recover motor function a few hours after awakening. Regression of paroxysmal symptoms was noted in all cases. Although the patients continued to take anticonvulsants. The observation period was 6 months.Сonclusion. Surgical removal of cerebral metastases in the motor area allows achieving complete or partial regression of neurological symptoms. At the same time, the recovery period is short – from several hours to 14 days. It becomes possible to cancel glucocorticoids 7–10 days after the operation. Conditions are being created for the continuation of complex treatment of patients previously considered incurable.

Glioblastoma multiform^ is one of the most aggressive malignancies, wich standard of treatment not changed over the past decade, and the average life expectancy from diagnosis to death does not exceed two years in the most optimistic trials. The review examines the features of the glioblastoma microenvironment, its genetic heterogeneity, the development of recurrent glioblastoma, the formation of drug resistance, the influence of the blood-brain barrier and the brain lymphatic system on the development of immunotherapy and targeted therapy. Molecular subgroups of glioblastomas with an assumed prognostic value were analyzed. It was determined that numerous relationships between glioblastoma cells and the microenvironment are aimed at ensuring tumor progression, and also cause a state of reduced effector function of T cells. Data on the development of future molecular-targeted therapies for four types of cancer cells based on their different properties and response to therapy are summarized: primary GSC, RISC cells, and proliferating and postmitotic non-GSC fractions. The penetration of blood-brain barrier with chemotherapeutic drugs and antibodies currently remains the main limitation in the treatment of glioblastoma. The resulting analysis of the causes is reduced to the following conclusions. A detailed understanding of the evolutionary dynamics of tumor progression can provide insight into the related molecular and genetic mechanisms underlying glioblastoma recurrence. The most promising methods of treatment for glioblastoma are combined therapy using immune checkpoint inhibitors in combination with new treatment methods -vaccine therapy, CAR-T-cell therapy and viral therapy. A deeper study of the mechanisms of drug resistance and acquisition resistance, biology and subcloning clonal populations of glioblastoma and its microenvironment, with active consideration of combined trips to the treatment will increase the survival rate of patients, and may lead to stable remission of the disease.

Brain metastases from clear cell uterine carcinoma are extremely rare and are associated with a poor prognosis.Case report. A case of metastasis to the cerebellum in a 55-year-old patient with uterine adenocarcinoma is presented. The diagnosis of uterine cancer T2N1M1, stage IV was established in 2016. Extirpation of the uterus, lymph node dissection, radiation and chemotherapy were performed. In 2018, the patient developed neurological symptoms. On MRI scan a tumor in the posterior cranial fossa was found. Without progression in other organs and the area of the primary focus. The tumor was resected. Histology: brain metastasis from clear cell uterine adenocarcinoma. Radiation and chemotherapy were performed. The patient’s neurological symptoms regressed. In the future, a complete response to the treatment was recorded.Discussion. Our case illustrates a rare metastasis from clear cell uterine adenocarcinoma. Brain metastases from uterine adenocarcinoma do not have a specific radiographic feature. Management of such patients should include a combined treatment, which can increase life expectancy. The life expectancy of our patient at the time of the control examination was 29 months.

Esophageal cancer spreads locally via the circulatory and lymphatic systems and can, extremely rarely, form brain metastases. The development of intracranial metastases is a long-term adverse event indicating poor prognosis. In this paper, we present a case of esophageal cancer with a brain metastasis in a patient who received combination therapy and demonstrated long-term progression-free survival.

Cerebral metastases occur with 10 to 30 % of all oncological patients. Hemorrhages into cerebral metastases are one of the most dangerous complications of the metastatic process. With that, cerebral metastases of such widespread solid malignant tumors as melanoma, kidney cancer, germ cell tumors, less frequently, lung cancer and breast cancer are prone to hemorrhages. The purpose of the work is to improve the results of surgical treatment of patients with brain metastases complicated with hemorrhages.Materials and methods. Surgical treatment of 69 patients with brain metastases complicated with hemorrhages was performed in N.N. Blokhin Russian Cancer Research Center. Hemorrhage on the macroscopic level was confirmed intraoperatively and in accordance with the results of the morphological study of surgical drugs. Total microsurgical resection of one or several cerebral metastases with hemor rhages was performed regarding all patients studied. The time interval of observation of patients after the surgical treatment comprises 1 to 72 months. There were 27 women and 42 men. The age range was from 18 to 74 y.o. Besides, the state of veins of lower extremities and the state of the coagulation blood system in accordance with the data of coagulograms was studies. The analysis of the macrostructure and the microstructure of metastases with hemorrhages as well as the morphological study of the brain tissue adjacent to hematomas was performed with a morphological study and histological techniques. The patients were distributed in accordance with the RPA (recursive partitioning analysis) classes: I class (n = 7), II class (n = 39), III class (n = 23); in accordance with the hemorrhage type: intratumoral type (26 metastases), perifocal type (20), mixed type (32); in accordance with the histological principle: melanoma (n = 25), lung cancer (n = 13), kidney cancer (n = 17), breast cancer (n = 4), colorectal cancer (n = 1), soft tissue sarcoma (n = 4), non-seminomatous germ cell tumor (n = 5).Results. Early post-surgical lethality comprised 6 % (n = 4). Development of local relapses comprised 16 % (n = 11). Extracerebral development of the disease has become the reason of death of 59 % of patients, development of the disease in the brain has become the reason of death of 41 % of patients. The shortest survival median was found with patients suffering from melanoma and comprised 6 months, with the III class of RPA, it comprised 6 months, with the perifocal hemorrhage type, it comprised 6 months, the longest survival median was found with patients suffering from sarcoma and comprised 15.5 months, with the I class of RPA, it comprised 14 months, and with the intratumoral hemorrhage type, it comprised 14.5 months.Conclusions. Development of local relapses depended on the surgical intervention technique and did not depend on the availability of tumor elements in the hematoma. Separated resection of the metastasis and perifocal hematoma does not violate oncosurgical principles and does not cause the rate of local relapses; the common survival median of patients after surgical treatment comprised 9 months. The factors that determined survival of patients with cerebral metastases with hemorrhages were the histological form of the primary tumor, type of metastasis hemorrhage and RPA class of the patient prior to the surgery.

In patients with kidney cancer (KC), the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authors’ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases) in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC.