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).

Stereotactic radiosurgery has firmly entered the arsenal of methods for treating vestibular schwannomas along with traditional surgical removal, providing high control of tumor growth and a low level of functional complications. Meanwhile, there is evidence of a possible relationship between the irradiation performed and the subsequent development of non-occlusive hydrocephalus. Purpose: to retrospectively assess the current level of development of hydrocephalus after stereotactic radiosurgery for vestibular schwannomas. Materials and methods: of 541 patients who received treatment with the Gamma Knife for unilateral vestibular schwannoma, 456 (84.3%) patients initially had no signs of non-occlusive hydrocephalus (group 1), while in 85 (15.7%) patients, MRI signs of internal non-occlusive hydrocephalus were revealed at the time of radiosurgery (group 2), of whom in 1 case VP shunting had previously been performed. In all cases, non-occlusive hydrocephalus at the time of SRS had a compensated course without clinical manifestations. Results: after radiosurgery, the development of de novo non-occlusive hydrocephalus in 7 (1.5%) patients from group 1 and its progression in 11 (12.9%) patients from group 2 were noted. The overall incidence of non-occlusive hydrocephalus after radiosurgery was 3.3%. Ventriculoperitoneal shunting was required in 3 cases in group 1 and 7 cases in group 2 due to the occurrence of neurological symptoms (1.8%). Conclusion: In some cases, radiosurgery can lead to decompensation of existing non-occlusive hydrocephalus, but it rarely occurs de novo. The asymptomatic course of non-occlusive hydrocephalus allows for SRS, as the risk of decompensation with subsequent need for VP shunting is low. Patients with non-occlusive hydrocephalus before SRS require more careful monitoring with assessment of neurological status and control MRI.

Vestibular schwannomas are the most common tumors in the cerebellopontine angle. Stereotactic radiosurgery is included in the armamentarium of methods for treating these tumors along with surgical treatment. Given the annual incidence of more than 15 radiosurgical cases of vestibular schwannomas per 1 million population, the expected need for stereotactic radiosurgery of these tumors in Russia is more than 2000 cases annually.Stereotactic radiosurgery is located at the intersection of several clinical specialties: neuroradiology, neurosurgery and radiation therapy, each of which has made a significant contribution to the development of this treatment method. The most commonly used for this is the cobalt‑based Leksell Gamma Knife, specifically intended for the treatment of intracranial neoplasms. Treatment is also possible with modern linear accelerators and proton accelerators, which provide high accuracy and conformity of irradiation. The experience gained since the first application of this method in the treatment of vestibular schwannomas has made it possible not only to optimize the radiation doses to the tumor and adjacent critical structures (brain stem, inner ear), but also to study the features of post‑radiation micro‑ and macro‑ changes, their impact on the clinical course, to develop recommendations for radiosurgery with schwannomas of various sizes. All this contributes to high control of tumor growth and a low level of functional disorders, which, along with easy tolerability and minimal hospitalization time, determines lower cost of this treatment compared to the traditional surgical approach and significant social and economic effect.This lecture is intended for neurosurgeons and radiation therapists and focuses on the most significant factors that influenced the development, promotion and active use of stereotactic radiosurgery of vestibular schwannomas in cli nical practice.

INTRODUCTION Stereotactic radiosurgery is one of the main treatments for vestibular schwannomas (VS). Their feature is frequent post-radiation pseudoprogression. This may be due to hormonal status of patients. OBJECTIVE To analyze expression of progesterone and estrogen receptors in women and men with VS. MATERIAL AND METHODS Immunohistochemical analysis of expression of progesterone (PR) and estrogen receptors (ER) after biopsy was performed in 240 patients with VS between 2018 and 2021. ER/PR expression was assessed in men (n=120) and women (n=120) in 3 age subgroups: young age (18-44 years), middle age (45-59 years) and old age (60-79 years). Each subgroup included 40 patients. Statistical analysis was performed using the Mann-Whitney test and MedCalc software. RESULTS ER expression is not typical for VS (men - 1 (0.01%), women - 3 (2.5%)). At the same time, PR expression was found in 29 (24.2%) men and 21 (17.5%) women. We found no significant difference in expression of ER and PR between men and women. However, variability in PR expression was revealed, i.e. predominance of this indicator in young women (p=0.0463) and middle-aged men (p=0.0110). Expression of PR was similar in elderly patients (p=0.2382). CONCLUSION The established incidence of PR expression may be one of the probable causes affecting development and duration of VS pseudoprogression after radiosurgery without clear relationship between sex and age. Further prospective research is needed to predict the risks of pseudoprogression.

Post-resection or isolated hypofractionated stereotactic radiotherapy (HF-SRT) is a therapeutic option for large brain metastases (>2 cm, LBMs).OBJECTIVE:To compare the results of post-resection or isolated HF-SRT in patients with LBMs.MATERIAL AND METHODS:A prospective study included 115 patients with 129 intact LBMs and 133 patients with 149 resected LBMs who underwent HF-SRT. Median baseline focal size was 22.5 and 28 mm, median target volume - 8.3 and 23.7 cm3, respectively.RESULTS:Median follow-up was 13.9 months, median overall survival - 19.1 months. After 12 months, local recurrences developed in 17 and 31% of patients, respectively (p=0.0078). Local recurrence after 12 months developed in 23% of patients with residual tumor in postoperative cavity compared to 16% of patients after total resection (p=0.0073). After 12 months, incidence of leptomeningeal progression was 27 and 11%, respectively (p=0.033), incidence of symptomatic radiation-induced necrosis - 4 and 23%, respectively (p=0.0006).CONCLUSION:Post-resection HF-SRT demonstrated better local control and less severe symptomatic radiation-induced necrosis compared to patients with intact LBMs. Incidence of leptomeningeal progression is significantly higher after resection of LBMs.

Stereotactic radiosurgery of vestibular schwannoma is an effective and safe method of treatment. The phenomenon of schwannoma pseudo-progression (transient post-radiation enlargement) complicates assessment of the outcomes after radiosurgery.OBJECTIVE:To investigate the changes of vestibular schwannoma in different periods after radiosurgery.MATERIAL AND METHODS:We analyzed early and long-term radiation-induced changes in 333 patients who received Gamma Knife treatment at the Burdenko Neurosurgery Center between April 2005 and December 2015. Mean follow-up period was 60 months (range 15-167). There were 89 men (26.7%) and 244 (73.4%) women. Mean age of patients was 48.2 years. Mean baseline tumor volume was 4.1 cm3 (range 0.1-14.5). Dynamics of changes was assessed using volumetric comparison.RESULTS:Tumor shrinkage without pseudo-progression was observed in 149 (44.7%) patients. Typical pseudo-progression in different variants was found in 131 (39.3%) patients, i.e. short-term (1 year) and long-term (≥2 years) course, complete and incomplete process. Eleven patients had atypical pseudo-progression after initial tumor shrinkage. Progression-free 5- and 10-year survival in the entire group was 87 and 81%, respectively. Progression-free 5-year survival rate was 95 and 92% in patients with and without pseudo-progression, respectively. Ten-year survival rate was 89 and 89%, respectively.CONCLUSION:Knowledge of pseudo-progression features is essential for the most reasonable and reliable assessment of treatment results and justification of timing and frequency of subsequent MR control. Atypical course of pseudo-progression can simulate tumor recurrence. In case of tumor enlargement at any follow-up stage after radiosurgery, advisability of surgery should be determined considering clinical data and likelihood of tumor shrinkage following natural regression of post-radiation tumor enlargement.

The study objective is to present the results of the treatment of metastatic brain patients by the staged radiosurgery with the Gamma Knife.Materials and methods. The retrospective analysis included 31 patients (13 men and 18 women) with brain metastases, whose radiosurgery treatment was carried out in 2 sessions. The operation was contraindicated in all patients due to the risk of neurological deficits or due to the high anesthesiological risk.Results. Local control of metastases growth was achieved in 31 (96.9 %) of 32 foci 3 months after treatment, and in 92.5 and 83.8 %, after 6 and 12 months, respectively. The age <50 years were associated with higher progression-free survival respectively. The median time of grade I–II radiation complications was 3.0 months, complications were observed in 11 (45.8 %) of 24 patients. Radiation complications of grade II (perifocal edema) were observed in 8 (33.3 %) patients, grade III (radionecrosis) – in 2 (8.3 %) patients. Overall survival at 6 and 12 months was 55.6 and 40.8 %, respectively (median 6.9 months), in patients receiving antitumor drug treatment – 80.0 and 56.8 %, respectively. All patients who did not received antitumor drug therapy died within 6 months.Conclusion. Two-stage radiosurgery, carried out in 2 sessions with an interval of 2–4 weeks, provides satisfactory local control with an acceptable level of post-radiation complications. This method of treatment can be used in patients with large brain metastases who are not subject to surgical treatment.

The review examines the epidemiology of vestibular schwannomas (VS), classification, the pathogenesis of the main clinical symptoms of small tumors located in the internal auditory canal (intracanalicular), the principles of diagnosis and various treatment options. The main directions of curation of patients with intracanalicular VS are analyzed: observation, radiosurgery and microsurgery. The main advantages and disadvantages of the methods used are considered: observation is advisable in the absence of VS growth, with initially safe hearing or with completely lost hearing. Radiosurgery has a high chance of preserving hearing, including functional, and provides control of VS growth in more than 90 %. There is currently insufficient data to recommend microsurgery as the first choice in the treatment of intracanalicular VS.

Изучить показатели общей (ОВ) и беспрогрессивной выживаемости пациентов с впервые выявленными диффузными астроцитомами (WHO Grade II) с низким индексом пролиферативной активности после комбинированного лечения. Оценить влияние различных факторов на показатели выживаемости. Материал и методы. Проведен анализ результатов лечения 153 пациентов (73 мужчины и 80 женщин) с впервые выявленными диффузными астроцитомами (WHO Grade II) с низким индексом пролиферативной активности (менее 5%). Среднее время клинического наблюдения составило 4,8±2,71 года. Результаты. В ходе однофакторного анализа выявлено, что на выживаемость без прогрессии влияют распространенность опухоли (р=0,01) и проведенная после операции лучевая терапия (р=0,0747). На ОВ оказывали влияние неврологический дефицит до хирургического лечения (р=0,0092), распространенность опухоли (р=0,0799) и степень хирургической резекции (p=0,0377). В ходе проведения многофакторного анализа статистически значимыми факторами прогноза ОВ были головная боль (р=0,0338), размеры опухоли (р=0,0102) и полнота резекции (р=0,0164). Что касается выживаемости без прогрессии, статистически значимыми были головная боль (р=0,0119), размеры опухоли (р=0,0001), послеоперационные осложнения (р=0,0196) и перенесенная после операции лучевая терапия (р=0,0496). Выводы. Значимыми прогностическими факторами являются размеры опухоли до хирургического лечения и полнота хирургического лечения; лучевая терапия улучшает выживаемость без прогрессии, не влияя на ОВ. Objective. To study the indicators of overall (OS) and disease-free survival in patients with newly diagnosed diffuse astrocytomas (WHO Grade II) with a low index of proliferative activity after combination treatment. To assess the influence of various factors on survival rates. Material and methods. The analysis of the treatment results of 153 patients (73 men and 80 women) with newly diagnosed diffuse astrocytomas (WHO Grade II) with a low index of proliferative activity (less than 5%) was carried out. The mean time of clinical follow-up was 4.8±2.71 years. Results. The univariate analysis revealed that disease-free survival was influenced by: tumor extent (p=0.01) and postoperative radiation therapy (p=0.0747). OS was influenced by the presence of neurological deficit before surgical treatment (p=0.0092), tumor extent (p=0.0799) and the volume of surgical resection (p=0.0377). During the multivariate analysis, statistically significant factors in the prognosis of OS were headache (p=0.0338), tumor size (p=0.0102) and resection completeness (p=0.0164). As for disease-free survival, statistically significant were headache (p=0.0119), tumor size (p=0.0001), postoperative complications (p=0.0196), and postoperative radiation therapy (p=0.0496 ). Conclusions. Significant prognostic factors are tumor size before surgical treatment and completeness of surgical treatment; radiation therapy improves disease-free survival without affecting OS.

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.

Глиомы низкой степени злокачественности (ГНСЗ, WHO Grade II) представляют собой опухоли нейроэпителиального происхождения, составляя от 15 до 45 всех первичных опухолей головного мозга. По данным H .Ohgaki и P. Kleihues (2005), среднее время прогрессии глиомы до глиобластомы составляет 5,3 года, а от WHO Gr III до глиобластомы 1,4 года. Медиана общей выживаемости при ГНСЗ 186 месяцев, 5-летняя общая выживаемость от 54,6 до 88,4, безрецидивная 5-летняя выживаемость от 37 до 55 8-летняя безрецидивная выживаемость 37, а 10-летняя общая выживаемость 67,1. Продолжительность жизни пациентов с впервые выявленными глиомами составляет в среднем от 6 до 8 лет, но может достигать, по данным некоторых исследований, и 20 лет. В 80 случаев у пациентов с ГНСЗ развивается симптоматическая эпилепсия, значительно снижающая качество жизни. В связи с необходимостью максимально радикального удаления опухоли с захватом эпилептогенной зоны, принимая во внимание диффузный рост и отсутствие четких границ опухоли, а также частую локализацию в функционально значимых зонах, многие хирурги рекомендуют использовать интраоперационную электрокортикографию и нейрофизиологический мониторинг. Лучевая терапия является важным этапом лечения после хирургического удаления опухоли. Лучшие результаты безрецидивной выживаемости пациентов (5,3 года) были в группе пациентов, которым была проведена ранняя послеоперационная лучевая терапия, в отличие от группы, где лучевая терапия не проводилась (3,4 года) показатель общей выживаемости в обеих группах статистически не различался. По данным исследований, применение высоких доз облучения (4550 Гр) не улучшало прогноз, при этом риск отдаленной токсичности возрастал. Рекомендованной дозой при лечении впервые выявленных ГНСЗ у взрослых могут быть дозы в интервале 4550,4 Гр. Low-grade gliomas (LGG, WHO Grade II) are tumors of neuroepithelial origin, accounting for 15 to 45 of all primary brain tumors. According to H.Ohgaki and P. Kleihues (2005), the average time for the progression from glioma to glioblastoma is 5.3 years, and from WHO Gr III to glioblastoma - 1.4 years. The median overall survival for LGG is 186 months, the 5-year overall survival varies from 54.6 to 88.4, and the relapse-free 5-year survival rate is 37 - 55 The 8-year relapse-free survival rate is 37, and the 10-year overall survival rate is 67.1. The life expectancy of patients with newly diagnosed gliomas averages from 6 to 8 years, but can reach, according to some studies, 20 years. In 80 of cases, symptomatic epilepsy develops in patients with LGG, significantly reducing quality of life. Due to the need for the most radical removal of the tumor with the capture of the epileptic zone, taking into account the diffuse growth and the lack of clear tumor boundaries, as well as frequent localization in functionally significant areas, many surgeons recommend the use of intraoperative electrocorticography and neurophysiological monitoring. Radiation therapy is an important treatment stage after surgical removal of the tumor. The best results of relapse-free survival of patients (5.3 years) were in the group of patients who underwent early postoperative radiation therapy, in contrast to the group where radiation therapy was not performed (3.4 years) overall survival in both groups was not statistically different. According to research data, the use of high radiation doses ( 4550 Gy) did not improve the prognosis, while the risk of long-term toxicity increased. The recommended dose for the treatment of newly diagnosed STN in adults may be in the range of 4550.4 Gy.

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status. Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies radiation therapy for limited brain metastases patients.

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.