В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.OBJECTIVE:To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer.MATERIAL AND METHODS:Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity).RESULTS:The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months.CONCLUSION:Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.

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.

Leptomeningeal carcinomatosis (LMC) in ovarian cancer is a rare complication of malignant gynecological disease, which is characterized by the spread of tumor cells through the cerebrospinal fluid to the membranes surrounding the brain and spinal cord. The cause of rare involvement of central nervous system (CNS) meninges in ovarian cancer is unclear. To date, there are no clinical guidelines for the management of this category of patients, and treatment of LMC in ovarian cancer is based on treatment protocols for meningeal carcinomatosis in other nosologies and on selected clinical observations presented in the world literature and personal experience. This article presents a clinical case of a patient with BRCA1-associated ovarian cancer and lesions of CNS meninges and parenchyma and our own experience in the treatment of this pathology. The treatment consisted of systemic anti-cancer therapy in combination with radiation therapy. Survival time after diagnosis of CNS metastases and treatment was 8 months. Key words: ovarian cancer, meningeal carcinomatosis, brain metastases, cytological examination, cerebrospinal fluid

Introduction. Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients. Median overall survival for this pathology varies between 3 and 12 months, and only 5 % of patients live for more than 5 years. Current treatment methods allow to slightly increase lifespan of the patients with glioblastoma but not in all cases.Aim – to determine the utility of full exome sequencing of biopsy materials of patients with glioblastoma using expanded gene panel for prescription of new targeted therapy.Materials and methods. The study included 28 patients with glioblastoma multiforme. Foundation One CDx assay was performed using DNA extraction from a paraffin block and next-generation sequencing. In total, 4 classes of genomic changes in 324 genes, introns of 34 genes taking part in rearrangements, as well as microsatellite instability and tumor mutation load were evaluated. For every tumor profile, individual therapy options were identified in accordance with the current knowledge, references for the relevant scientific studies were included. From some patients, feedback was received allowing to evaluate the dynamics of their condition and changes in therapy after the performed study.Results. Genes in which mutations are the most common were identified: EGFR – in 11 patients, CDKN2A – in 13, TP53 – in 9, TERT (frequent mutations in TERT gene promoters с.-124C>T and c.-146C>T) – in 15, MTAP – in 10. Mean mutation level was 4.5 mutations/ MB and tumors did not have microsatellite instability. For 6 patients, appropriate targeted therapy was identified.Conclusion. Sequencing using an extended gene panel is justified and recommended for patients with glioblastoma multiforme for selection of new targeted therapy.

Introduction. Treatment of patients with brain metastases is an important problem that should be considered in the framework of combination approach. Introduction of new techniques of drug therapy as well as radiotherapy and neurosurgical treatment allows to significantly increase patient survival. Effective drug therapy and local control of brain metastases are of utmost importance in prediction of overall survival and patient quality of life.Aim. To investigate the prognostic factors for overall survival and intracranial progression (local recurrences, distant metastases) in patients with brain metastases of renal cancer after neurosurgical resection.Materials and methods. Retrospective analysis of the treatment results of 114 patients with metastatic brain lesions due to renal cancer who underwent neurosurgical resection (NSR) at the N. N. Blokhin National medical Research Center of Oncology was performed. Clinical data of 102 (89.5 %) of 114 patients for whom data on survival was available were evaluated. Among them, 80 (78.4 %) of patients died, 22 (21.5 %) are under observation. Extracranial disease status at the time of NSR was known in 82 (71.9 %) patients: 45 (54.8 %) patients had extracranial metastases, and 37 (45.1 %) did not. Total resection of brain metastases with perifocal and perivascular zones was performed in 92 (90.1 %) patients; in other cases, fragmental lesion resection was performed.Results. median overall survival after NSR was 13.8 months (95 % confidence interval 10.3–18.6). per study data, factors affecting overall survival of patients with brain metastases of renal cancer after neurosurgical resection were presence / absence of extracranial metastases and patient’s functional status. Local recurrences in the postoperative cavity after NSR were observed in 24 (21 %) of 114 patients. median time of local recurrence was not achieved. Statistically significant factor of high risk of recurrence in the postoperative cavity was presence of lesions with maximal diameter ≥2 cm. Development of new (distant) metastases was observed in 31 (27.2 %) of 114 patients. median survival without distant metastases in patients with brain metastases after NSR was not achieved. frequencies of distant metastases at 6, 12 and 24 months were 15.5; 24.1 and 35.8 % respectively. per multifactor analysis, factors affecting development of distant metastases in the brain after NSR are multiple metastatic brain lesions and presence of extracranial metastases.Conclusion. Neurosurgical resection in patients with cerebral metastases of renal cancer in the total group leads to median overall survival of 13.8 months. predictors of better overall survival are absence of extracranial metastases and high functional status.

According to the literature, metastatic brain damage in kidney cancer occurs in 6.5 % of patients. The introduction of new techniques associated with the use of targeted drugs, immune checkpoint inhibitors and innovative radiation therapy techniques can significantly increase patient survival. Effective drug therapy and local control of brain metastases are of paramount importance for predicting overall survival and quality of life for patients. This literature review summarizes the scientific literature data on the use of local and systemic methods of treatment in patients with metastases of kidney cancer to the brain.

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.

The spread of female genital tract tumours to the brain is a rare and insufficiently studied pathology. The problems of diagnosis and treatment of this group of patients still remain. The article gives a detail account of the clinical picture, radiological and morphological diagnosis, and the principles of treating patients with brain metastases from gynaecological cancers. Conclusion. A probable cause of a rare occurrence of brain metastases from gynaecological malignancies might be a high resistance of nervous tissue to various kinds of tumours. When local control over a brain tumour is achieved, this might improve the patient’s survival and quality of life in some particular cases. Key words: ovarian cancer, endometrial cancer, cervical cancer, brain metastases

Metastatic damage to the brain is a frequent manifestation in tumors of various localizations, including breast cancer. Until recently, systemic therapy of metastatic brain damage was of limited use; however, with the advent of targeted drugs that are better understood in terms of the specific molecular targets and biological characteristics of metastases, it is now possible to improve treatment results. In an analysis of the results of studies on the problem of metastasis of breast cancer in the brain, a comparison of the use of various targeted drugs in the treatment of metastatic HER2 + breast cancer is presented. The results of a comparison of the degrees of effectiveness of targeted drugs, both in monotherapy and in combination with chemotherapy, were obtained and analyzed.

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.

Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

Despite the fact that melanoma is a tumor of visual localization, mortality from skin melanoma remains one of the leading causes of mortality worldwide. Early metastasis of melanoma, even during the initial stages of the tumor process, indicates a high malignant potential of the tumor. Moreover, metastatic melanoma is resistant to current chemotherapy regimens, which is a significant problem today. Progression, resistance to drug therapy of skin melanoma is associated with a population of tumor stem cells, which are characterized by dysregulation of signaling pathways and aberrant phenotypes. The formation of tumor stem cells contributes to their microenvironment. Surface markers expressed by tumor stem cells include transporter proteins that mediate chemoresistance. The study of the microenvironment, the activity of the expressed antigenic determinants makes it possible to understand the processes of chemoresistance formation and to discover (develop) strategies for its overcoming. The article provides an analysis of the literature data on the significance of tumor stem cells in the development of drug resistance of melanoma.

Modern advances in oncology can achieve significantly better results in terms of life expectancy in patients with metastatic brain disease. The combination of surgery, systemic therapy, whole brain irradiation and local methods of radiation therapy lead to good indicators for controlling the manifestations of the disease in the brain. Of course, intensification of treatment increases the risk of iatrogenic complications. The use of aggressive stereotactic radiotherapy regimens leads not only to high local control of irradiated metastases, but also to the risk of so-called radiation necrosis. The use of the most up-to-date diagnostic methods does not always allow one to unequivocally differentiate radiation necrosis from continued metastasis growth. The above example shows the need for a careful assessment of such situations and a multidisciplinary approach to interpreting the results of stereotactic radiotherapy.

The article is devoted to the issue of clinical and neurological features of primary brain tumors (PBT). PBT account for 2% of the total number of human tumors. PBT represent an urgent social problem, causing disability and mortality. The incidence rate of primary tumors of the brain and other parts of the central nervous system in the United States from 2011 to 2015 amounted to 23.03 cases per 100,000 population. The most common histological types of PBT: meningioma (36.4%), pituitary tumors (15.5%)and glioblastoma (15.1%).The clinical picture of PBT is represented by cerebral and focal symptoms. Neurological deficit is determined by the location and volume of the neoplasm.The initial manifestations of tumor growth may be symptoms of irritation of the squeezed area of the brain tissue, which will be replaced later by symptoms of prolapse. Cerebral symptoms in most cases are associated with increased intracranial pressure and the development of cerebral edema. The subsequent development of the tumor process leads to the dislocation of brain structures and the formation of wedge syndromes. The most common clinical symptoms are: cognitive deficit (36%), convulsive syndrome (35%), headache (31%), ataxia (24%) and motor deficiency (22%).The article summarizes the data of world and domestic clinical studies aimed at determining the prevailing symptoms of primary brain tumors for the purpose of early diagnosis, timely medical care and assessment of the effectiveness of the treatment. Knowing the specifics of the clinical picture will significantly increase oncological alertness, which will lead to early diagnosis and timely treatment of PBT, which play a key role in improving the quality of life and increasing its duration.