[New classification and approaches to the treatment of schwannomatosis]. / Novaya klassifikatsiya i podkhody k terapii shvannomatozov.

Schwannomatoses is a new classification unit for all the hereditary diseases caused by chromosome 22 damage followed by multiple benign neoplasms of the peripheral and central nervous system. Schwannomatosis occurs as a result of damage to different genes: NF2, SMARCB1, LZRT1, loss of heterozygosity of the long arm of chromosome 22. Nevertheless, clinical manifestations are similar. Molecular diagnostics not only confirms the diagnosis, but also predicts the course of disease. Thus, the most severe clinical manifestations are observed in patients with violation of semantic sequences and reading frame shift in exons 2-13 of the NF2 gene. A more favorable course with less number of tumors is observed in patients with somatic mosaicism. Stereotactic irradiation and surgery are the main treatment options for schwannomatosis. However, there is evidence of effective targeted therapy with bevacizumab (inhibitor of vascular endothelial growth factor). Bevacizumab is used in patients with bilateral vestibular schwannomas and high risk of hearing loss, as well as for intramedullary tumor growth control.

[Prognostic value of TERT mutation in adults with primary glioblastomas. Preliminary results]. / Prognosticheskoe znachenie mutatsii gena TERT u vzroslykh patsientov s pervichnymi glioblastomami. Predvaritel'nye rezul'taty.

Glioblastoma (GB) is one of the most aggressive primary brain tumors. Analysis of molecular genetic factors affecting prognosis in patients with GB is an important direction of fundamental and clinical researches. There are literature data on the effect of TERT gene mutations, MGMT methylation and IDH1/2 status on overall survival in patients with GB. OBJECTIVE: To evaluate the incidence of TERT gene promoter mutations in adults with primary GB and to analyze the effect of TERT mutations on relapse-free and overall survival, as well as interaction of these mutations with MGMT gene methylation and IDH1/2 mutations. MATERIAL AND METHODS: The study included 56 patients (26 women and 30 men) with histologically verified GB in which genetic and molecular investigations were performed. There were patients with life duration >3 years (n=15) and people with an extremely unfavorable course of disease (14 ones with primary multiple GB, 8 patients with GB metastases including extraaxial and 8 patients with life duration <8 months). TERT gene sequencingwas performed in all the cases, IDH1/2 status was known for 41 patients, MGMT status - for 23 patients. RESULTS: Overall survival significantly differed between patients with and without TERT mutation (56 vs 17 months, p>0.05). TERT gene promoter mutation increased the effect of IDH1/2 mutations on overall and relapse-free survival (p=0.011). No TERT and IDH1/2 gene mutations worsened prognosis. There were no significant differences between TERT status and development of primary multiple GBs, as well as extra- and intracranial metastases. CONCLUSION: Thus, the combined status of IDH1/2 and TERT mutations was a factor of better prognosis and can be proposed in clinical practice.

[Treatment of primary craniofacial (sinonasal) malignant tumors affecting the anterior and middle skull base]. / Lechenie pervichnykh kraniofatsial'nykh (sinonazal'nykh) zlokachestvennykh opukholei, porazhaiushchikh perednie i srednie otdely osnovaniia cherepa.

Sinonasal malignant tumors are characterized by high histological variability and complexity of the differential diagnosis. Currently, there are classifications of these tumors, which are based on their localization and involvement of various anatomical structures. However, generally accepted algorithms for treatment of this pathology have not yet been developed. This review describes the most important algorithms for treatment of the most common histological variants of sinonasal malignant tumors: squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, esthesioneuroblastoma, adenoid cystic cancer, and sinonasal adenocarcinoma. The main problems in choosing the approach for treating these tumors are the lack of generally accepted resectability criteria and contradictions between oncological and neurosurgical indications for surgical treatment. Further research is needed to study the role of radiosensitizers and radioprotectors in comprehensive treatment of sinonasal malignant tumors.

[Investigation of the metabolic features of primary glioblastomas by Tc-MIBI SPECT/CT and evaluation of their effect on disease prognosis]. / Issledovanie metabolicheskikh osobennostei pervichnykh glioblastom metodom OFÉKT-KT s Tc-MIBI s otsenkoi ikh vliianiia na prognoz zabolevaniia.

OBJECTIVE: To study the effect of metabolic characteristics of the tumor determined by 99mTc-MIBI single-photon emission computed tomography (SPECT) and various molecular genetic features on the outcomes of combination treatment of hemispheric glioblastomas. MATERIAL AND METHODS: This single-center prospective cohort study involved 68 patients aged 25-78 years (38 males and 30 females) with primary glioblastomas. Hypermetylation of the promotor region of the MGMT gene was observed in 24 (42%) out of 57 patients. The IDH1 mutation was revealed in two (3.5%) patients. The catamnestic data were available for 66 out of 68 patients. The first SPECT/CT study was carried out before chemoradiation therapy; the second SPECT/CT study was performed after the chemoradiation therapy. In each study, quantitative measures were calculated for the early (15-30 min after the patient had received a radiopharmaceutical) and late (after 45-60 min) phases. RESULTS: The actuarial survival rates after 12 and 24 months were 69.6 and 29.1%, respectively. The median overall survival rate was 17.5 months (95% CI 12.9-20.3). Favorable prognostic factors for overall survival included the higher uptake index (UI) in the late phase compared to UI in the early phase of the first SPECT/CT study (p=0.0444), dynamics of changes in UI during the second SPECT/CT compared to baseline over 10% (p=0.0436), MGMT hypermethylation (p=0.0003), and duration of the period between surgery and initiation of chemoradiotherapy being <1 month (p=0.0008). No statistically significant correlations were revealed between the absolute UI values in the tumor and its molecular genetic features. CONCLUSION: The 99mTc-MIBI SPECT/CT can be used to predict overall survival and to plan radiation therapy of glioblastoma as it is more readily available at primary healthcare facilities than amino acid PET.

[Li-Fraumeni syndrome in a patient with multiple anaplastic oligodendrogliomas of the brain (a case report and literature review)]. / Sindrom Li-Fraumeni u patsienta so mnozhestvennymi anaplasticheskimi oligodendrogliomami golovnogo mozga (klinicheskoe nabliudenie i obzor literatury).

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation. OBJECTIVE: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain. CLINICAL CASE: A 42-year-old male patient presented with complaints of headaches, word finding difficulty, memory loss, right hemianopsia, and generalized convulsive attacks. For 10 years, he underwent multiple interventions and chemotherapy courses for colon adenocarcinoma and recurrent B-cell lymphoma. MRI revealed multiple space-occupying lesions of the cerebraln hemispheres, which were located in the left temporo-occipital and right frontal regions. RESULTS: The patient underwent resection of multiple space-occupying lesions of the left temporo-occipital and right frontal regions. The postoperative period proceeded without complications. The histological diagnosis was WHO grade III anaplastic oligodendroglioma. The patient and one of his sons were detected with a R248W missense mutation in the TP53 gene. The patient underwent six courses of temozolomide chemotherapy. At a follow-up examination 20 months after surgery and chemotherapy, the patient's condition was satisfactory; he returned to work. Control MRI of the brain revealed no signs of continued tumor growth. CONCLUSION: An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. The patient had a good quality of life and returned to professional activity.

[The 2016 WHO classification of primary central nervous system tumors: a clinician's view]. / Klassifikatsiia VOZ pervichnykh opukholei tsentral'noi nervnoi sistemy 2016 g.: vzgliad klinitsista.

This article is devoted to the latest edition of the 2016 WHO classification of primary CNS tumors. The authors, who are clinicians and not morphologists, have tried to analyze and briefly present the main changes to the new edition of the WHO classification of primary CNS tumors, the main difference of which from the previous 2007 classification is inclusion of the molecular genetic features of primary CNS tumors in the classification criteria. The article focuses mainly on the classification issues of diffuse gliomas and glioblastoma, with assessment of the role of IDH-1,2, ATRX, TERT, and MGMT mutations as well as a 1p/19q co-deletion. The article briefly describes some new nosological forms (e.g., Grade III anaplastic pleomorphic xanthoastrocytoma) and presents a new approach to the classification of embryonic (medulloblastoma) and glial childhood tumors as well as tables of the main differences between 2016 and 2007 WHO classifications of primary CNS tumors. Based on their own clinical experience, the authors dispute with the described classification and suggest their own ideas for improving the classification of primary CNS tumors in the future.

[Outcomes of application of modern first-line chemotherapy regimens in complex treatment of glioblastoma patients]. / Rezul'taty primeneniya sovremennykh rezhimov khimioterapii pervoi linii v kompleksnom lechenii patsientov s glioblastomoi.

OBJECTIVE: To describe a procedure and outcomes of comprehensive first-line treatment in glioblastoma patients. MATERIAL AND METHODS: We analyzed 107 glioblastoma patients operated on in 2010-2011. Seventy five patients underwent combined chemoradiotherapy (CRT) with simultaneous administration of 75 mg/m2 temozolomide (TMZ), followed by chemotherapy with 200 mg/m2 TMZ for 5 days, every 28 days. Separately, we examined 32 patients with large tumors who received alternative treatments. RESULTS: The median time to progression was 11.7 months in the study group and 7.2 and 8.1 months in groups of alternative therapy. The one-year progression-free survival rate was 37%. Overall survival was 29.2 months. CONCLUSION: The chemoradiotherapy regimen involving TMZ followed by one-year TMZ monotherapy is the appropriate treatment for patients with resected glioblastoma. With this approach, no tumor progression occurs in one third of patients during the first year. A careful study of the clinical and radiological findings in the course of treatment makes it possible to achieve the maximum efficacy, avoid unreasonably early switch to second-line therapy, and timely detect tumor recurrence signs. The Response Assessment in Neuro-Oncology (RANO) criteria should be used for assessment of MRI detected changes in the tumor size. The rates of overall and recurrence-free survival were significantly lower in patients with inoperable or partially resected tumors. The applied approaches provide only a slight advantage in control of tumor growth, which necessitates searching for more efficient treatment options for these patients. One of the approaches may be addition of bevacizumab to the first-line therapy regimen.