REVIEWERS
This article focuses on the latest edition of the World Health Organization (WHO) classification of primary tumors of the central nervous system (CNS), which was released in 2021, and the changes in it that may have an impact on clinical practice in neurooncology. The literature review considers a modern hybrid histo-molecular approach to the taxonomy and nomenclature of primary CNS tumors. The considered aspects of the 5th edition of the classification are necessary for pathologists and specialists in the field of neurooncology.
Introduction. According to the WHO CNS of tumors of central nervous system gemistocytic astrocytomas (GA) are common astrocytic tumors, in which the proportion of gemistocytes is at least 20 % of the total cell mass. Morpho-molecular characterization and treatment tactics of GA research is insufficient.
Purpose. Identification of risk factors for the development of early recurrence of gemistocytic astrocytes (GA).
Material and methods. A retrospective and prospective analysis of the identified signs, brain MRI data, features of morphological and molecular genetic diseases was performed in 14 patients diagnosed with GA. The work included patients older than 18 years with supratentorial invasive tumor. The patients were aged 27 to 62 years, the average temperature of the age was 35.5 years. There were 5 men. After the removal operation, histological, immunohistochemical and molecular genetic studies were performed. The histological diagnosis was made according to the WHO classification of CNS tumors and the AFIP atlas (2007). Real-time PCR revealed the presence of mutations in the IDH1/IDH2 genes and the combined deletion of 1p19q in all patients; in 10 patients, the level of gene expression was also observed: TP, VEGF, PDGFRA, β-tubulin, MGMT, C-kit, ERCC1.
Results. Median recurrence-free period (RFS) GA was 89 weeks. If a recurrence occurs before this time RFS is considered early. The odds ratio (OR) was calculated for different groups of early and late recurrence according to the standard method. Significantly, the risk of developing an early relapse of GA increased with the expression of the VEGF gene, ΔSt < 1.15 (p < 0.05) (OR — 121). Several risk factors were also identified that cause inflammation of GA recurrence, but without a statistical tumor: expression of the β-tubulin gene ΔSt < 0.65 (RR — 33), accumulation of tumor contrast. according to MRI of the brain (OR — 10.7), vascular proliferation (OR — 8.3), Ki-67 > 5 % (OR — 4.5), tumor spread in the area of opening of the cerebral hemispheres (OR — 4.5).
Conclusion. Features of brain MRI data, morphological and molecular-genetic picture These patients probably need complex treatment (surgery, radiation therapy, chemotherapy), which they currently do not meet.
Introduction. Due to the active research of the molecular and genetic features of glioblastoma, the performance of the biological processes occurring in tumor cells has become more distinct. In the modern scientific literature, the number of scientific studies is growing, which emphasizes the priority importance of the genetic status of the tumor in the prognosis of the disease.
Purpose statement. To study the influence of clinical and molecular genetic factors on the median of the first relapse-free period.
Materials and methods. The first progression-free survival (PFS) was analyzed in 30 patients aged 28 to 81 years with glioblastoma. The diagnosis was established in accordance with the WHO classification of CNS tumors in 2021. After the first operation, all patients underwent a course of radiation therapy (LT) (60Gr) and chemotherapy with temozolomide (2–18 cycles). In each case, clinical parameters such as the patient’s age, functional status on the Karnovsky scale both before and after surgery, features of the neuroimaging picture (prevalence of the tumor process, localization, tumor volume), treatment (degree of tumor resection, radiation therapy with or without temozolomide and the number of cycles of chemotherapy) and molecular genetic parameters of tumor (determination of the mRNA expression level of genes: MGMT, VEGF, PDGFRA, β-tubulin III, ERCC-1, TOP2A) were studied.
Results. Of all the studied clinical parameters, only the postoperative functional status on the Karnovsky scale (p = 0.001) influenced the median of PFS. The median of the first PFS was not affected by such radiological characteristics as involvement of basal structures of the brain in the tumor process (p = 0.9), the side of the lesion (p = 0.67), the prevalence of the tumor process (p = 0.6) and the volume of the tumor (p = 0.52). The duration of the first PFS with statistical reliability was higher in the group of patients after subtotal resection of the tumor (14.9 months; p ³ 0.05). The median of the first PFS was influenced by the presence of a mutation in the IDH1 gene (22.5 vs 11.5 months) and the expression level of the MGMT gene (p = 0.036). Total tumor resection increases the first BRP only at a high level of MGMT gene expression, although without statistically significant differences (7.6 vs 2.7 months; p = 0.6). The addition of temozolomide to radiation therapy (75 mg/m2, orally, daily) led to an increase in the first relapse-free period by more than 6.9 months, but only in patients with low expression of the MGMT gene in the tumor.
Conclusion. In the conditions of standard patient therapy (surgical removal of the tumor, chemoradiotherapy followed by adjuvant therapy with temozolomide), the first PFS primarily depends on the molecular genetic characteristics of the tumor, namely, the presence of a mutation in the IDH1 gene and the level of MGMT in the tumor. For patients with an expected lack of response to therapy (i.e., a high level of MGMT gene activity), the role of other factors increases, and first of all, the volume of cytoreduction.
Progress in conservative anticancer treatment is associated with an increase in long-term side effects of drugs in patients with successfully treated oncology. Immune checkpoint-inhibitors (ICI) belongs to group of anticancer immunotherapy. The most life threating cardiovascular adverse event are Checkpoint-associated myocarditis. This review provides information about potential mechanisms of immune related adverse events of ICI, epidemiology and clinical features of Checkpoint-associated myocarditis.
Gestational trophoblastic disease (GTD) is a rare tumor characterized by spectrum of trophoblastic proliferative disorders associated with pregnancy. These neoplasms occur in less than 1% of female genital malignancies. There is a high curability of the disease even in the presence of disseminated process with the ability to preserve reproductive function. However, this is possible if timely diagnosis and adequate treatment tactics were applied. The article presents a review of the literature and the summary of guidelines of treatment of this malignancy.
In vitro and in vivo experiments often require construction of convenient cell instruments to reliably assess the specificity of the molecules or therapeutic approaches being tested against the protein target of interest. Using model isogenic cell lines that differ only in the expression of the target protein represents an ideal solution to this problem. Cloning and efficient delivery of genetic cassettes encoding such proteins, particularly the large ones, is typically challenging, much as the knock-out of the respective genes. To tackle this issue, we adapted a CRISPR/ Cas9-based SAM (Synergistic Activation Mediator) platform, and successfully established four model isogenic cell line pairs (U343, HeLa, HT-1080 и HEp-2) overexpressing human CD5.
Internal tandem duplication is the most common form of mutation in FMS-like tyrosine kinase 3 (FLT3) in different haematological malignancies, highlighting in acute myeloid leukaemia (AML) and is associated with increased risk of relapse and reduced overall survival. A major breakthrough in the treatment of FLT3-mutated AML has been achieved through the use of highly selective FLT3 tyrosine kinase inhibitors, both in monotherapy and in combination with standard intensive cytotoxic chemotherapy. The desire to improve the outcomes of patients with AML, including those with relapse and refractory disease, has led to attempts to use non-standard therapeutic options. Enhancement of the antileukemic effects of the second-generation FLT3 inhibitor Gilteritinib may be achieved through synergy with the hypomethylating agent 5-azacytidine and the selective Bcl-2 inhibitor Venetoclax. Thus, targeted triple therapy is a promising option in the treatment of patients with FLT3-mutated AML. This study sought to evaluate the effectiveness of “triple therapy” regimen in 4 patients with relapsed/refractory FLT3 mutated AML. We found that the use of this combination showed rapid response with good safety and frequently allowed subsequent transplant and achieve durable clinical benefit.
Advances in the understanding of the molecular biology of central nervous system (CNS) tumors have prompted a new WHO classification of brain and spinal cord tumors in 2021 and integration it in routine clinical practice. Nowadays accurate diagnosis verification consists not only of the histological tumor type, but also includes its molecular-genetic characteristics. Differences in the genetic features of a tumor, even within the same histological type, will determine differences in the prognosis of the disease, and in the tactics of anticancer therapy. The introduced changes necessitate a comprehensive diagnosis of CNS tumors, thereby placing the responsibility for formulating the final diagnosis not only on pathologists. New approaches to classification make it possible to personalize anticancer treatment, as well as including new methods of targeted and immunotherapy, which today seems to be a key aspect of improving the survival of this category of patients.
CLINICAL CASE
In the clinic of neurosurgical treatment of tumors of the brain and spinal cord, more and more cases of diagnosis in patients with primary multiple cerebral tumors of various histological structures began to occur. And although such clinical situations are still very rare, each of them requires a personalized treatment approach, and their careful study will provide valuable new information about the biology of carcinogenesis. This article demonstrates a rare case of the development of synchronous CNS tumors of various histological structures (glioblastoma and malignant meningioma) in a patient.
Prolactinoma and associated hyperprolactinemia is one of the main causes of infertility. The disease can develop within the framework of multiple endocrine neoplasia type 1 (MEN 1), and the management of such patients may differ from the treatment of sporadic forms. The article presents a clinical case of a patient with prolactinoma that developed as part of MEN1 syndrome who planned pregnancy. An individual approach to the choice of therapeutic tactics was demonstrated, which allowed solving the problem of restoring fertility.
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