[Results of hypofractionated stereotactic radiotherapy for resected and intact large brain metastases]. / Rezul'taty stereotaksicheskoi radioterapii v rezhime gipofraktsionirovaniya krupnykh metastazov v golovnom mozge posle khirurgicheskoi rezektsii i v samostoyatel'nom variante lecheniya.

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 irradiation for optic nerve hemangioblastoma associated with Von Hippel-Lindau disease: a case report and literature review]. / Stereotaksicheskoe obluchenie gemangioblastomy zritel'nogo nerva, assotsiirovannogo s bolezn'yu fon Gippelya­Lindau: klinicheskii sluchai i obzor literatury.

Hemangioblastoma is a benign tumor of the central nervous system arising sporadically or as a component of Von Hippel-Lindau disease. Von Hippel-Lindau disease is a rare autosomal dominant hereditary syndrome with various phenotypes caused by VHL gene variants. To date, only about 40 cases of optic nerve hemangioblastoma have been described in the literature. Stereotactic irradiation may be effective for supratentorial hemangioblastomas including lesions of optic nerves. The authors describe a rare case of stereotactic irradiation of intraorbital hemangioblastoma of the optic nerve in a patient with Von Hippel-Lindau disease.

Long-Term Results of the First Clinical Application of Stereotactic Radioablation Using a Linear Electron Accelerator for the Treatment of Ventricular Tachycardia.

We present the first clinical application of non-invasive stereotaxic radioablation of ventricular tachycardia (VT) refractory to medical and surgical treatment. Based on the results of invasive navigational activation mapping, a pericicatrical zone in the interventricular septum associated with VT was verified. Radiosurgical irradiation of the target in the region of the interventricular septum and the posterior apical segment of the left ventricle was performed on a TrueBeam linear electron accelerator (Varian) in accordance with the segmental scheme of the left ventricle. Irradiation doses for 95% of the internal target volume (ITV, 17 cm3) and planned target volume (PTV, 46 cm3) (31.2 and 25 Gy, respectively) were delivered by two full coplanar arches in 1 session. Irradiation was performed during expiration using a respiratory control system. The loading dose to critical structures was within tolerance. The planned follow-up period is 6 months. According to remote monitoring, the intensity of VT paroxysms over 48 days after treatment was from daily to 2-3 per day. Then, the incidence of VT paroxysms decreased (1-3 per week), and from the 64th to the 185th day (the end of the observation period), no VT paroxysms were recorded, which suggests that the impact was highly precise, conformal, and involved the total wall thickness. No undesirable effects and damage to adjacent organs were observed.

[Hypofractionated stereotactic irradiation for optic nerve glioma]. / Stereotaksicheskoe obluchenie gliom zritel'nogo nerva v rezhime gipofraktsionirovaniya.

Optic nerve glioma is a rather rare tumor. It predominantly arises in pediatric patients, including those with type I neurofibromatosis. This neoplasm is accompanied by decreased visual function and exophthalmos. Treatment strategy is individualized depending on age, volume and spread of tumor, as well as severity of clinical manifestations. Possible treatment options are surgical resection, chemotherapy, radiotherapy and their combination. Radiotherapy can be recommended for patients with intact visual functions, no severe proptosis and trophic lesions. Classic fractionation mode is used as a standard. Currently, the possibility of hypofractionated irradiation is being considered. OBJECTIVE: To evaluate safety and efficacy of hypofractionated radiotherapy in patients with optic nerve glioma. MATERIAL AND METHODS: Sixteen patients with optic nerve gliomas underwent hypofractionated stereotactic irradiation (CyberKnife) between May 2014 and October 2019. Single focal dose was 5.5 Gy. There were 5 fractions up to total focal dose of 27.5 Gy. The sample enrolled 14 children with a median age of 4 years (range 23 months - 13 years) and 2 adults aged 47 and 66 years, respectively. Median of tumor volume was 2.77 cm3 (range 1.69-10.01 cm3). RESULTS: Tumor growth control was achieved in all patients, partial remission was observed in 5 (32%) patients. None patient had deterioration of visual function. Improvement of visual acuity was noted in 3 (19%) cases. Visual field enlargement occurred in 4 (67%) out of 6 patients who were preoperatively examined. After irradiation, proptosis decreased by ≥ 1 mm in 9 (60%) out of 15 patients.

[Cell cultures in assessing radioresistance of glioblastomas]. / Ispol'zovanie kletochnykh kul'tur dlya otsenki radiorezistentnosti glioblastom.

To date, no modern methods of treatment allow overcoming malignant potential of glial neoplasms and significant increase of survival. Analysis of glioblastoma radioresistance using cancer cell cultures is one of the perspective directions, as radiotherapy is standard and available treatment method for these neoplasms. This review summarizes current studies identifying many factors of radioresistance of glial tumors, such as hypoxia, microenvironment and metabolic features of tumor, stem cells, internal heterogeneity of tumor, microRNA, features of cell cycle, DNA damage and reparation. We obtained data on involvement of various molecular pathways in development of radioresistance such as MEK/ERK, c-MYC, PI3K/Akt, PTEN, Wnt, JAK/STAT, Notch, etc. Changes in activity of RAD51 APC, FZD1, LEF1, TCF4, WISP1, p53 and many others are determined in radioresistant cells. Further study of radioresistance pathways will allow development of specific target aptamers and inhibitors.

[Radiosurgery for recurrent glioblastoma]. / Radiokhirurgicheskoe lechenie retsidivov glioblastom.

BACKGROUND: Despite the combined treatment in accordance with modern standards, recurrent glioblastoma usually occurs within several months after resection and causes low relapse-free and overall survival. One of the most effective methods for malignant glioma progression is repeated radiotherapy. Indications for this approach have expanded after introduction of stereotactic irradiation into routine clinical practice. OBJECTIVE: To evaluate the results of radiosurgery in patients with recurrent glioblastoma and to identify the factors determining its effectiveness. MATERIAL AND METHODS: Radiosurgery has been carried out in 168 patients with relapses of glioblastoma between 2005 and 2021. This study enrolled 88 patients with 180 foci of local and distant progression. Mean age of patients was 42.8±2.1 years (range 4-73). Mean period between diagnosis and repeated irradiation was 12.7 months. Mean volume of focus was 2.4 cm3, mean dose - 20 Gy. Median follow-up period after radiosurgery was 11.2 months. RESULTS: Repeated irradiation with correction of systemic therapy improved progression-free survival and overall survival with insignificant radiation-induced toxicity. Annual overall survival was 62.2%, median of overall survival after radiosurgery - 15.1 months. Significant factors of local control were marginal dose of at least 18 Gy and distant relapse. Median of progression-free survival in the group of distant progression of glioblastoma was only 3.6 months vs. 9.1 months in patients with local recurrence. CONCLUSION: Repeated irradiation in radiosurgery mode with a dose of 18 Gy and higher is an effective option for local treatment increasing progression-free and overall survival in patients with progression of glioblastoma.

[Changes in treatment paradigm for neurosurgical patients in the era of stereotactic irradiation. By the 15th anniversary of the Neuroradiosurgery in Russia]. / Izmenenie paradigmy lecheniya neirokhirurgicheskikh patsientov v epokhu stereotaksicheskogo oblucheniya. K 15-letiyu neiroradiokhirurgii v Rossii.

INTRODUCTION: Stereotactic method and new irradiation techniques ensured radiosurgical treatment with high precision and conformity and significantly expanded the indications for stereotactic irradiation in neurosurgery. MATERIAL AND METHODS: Over 15-year period, 29 976 patients underwent irradiation in various modes of fractionation on linear accelerators and Gamma Knife system at the first national radiosurgery center. RESULTS: Stereotactic radiotherapy and radiosurgery are followed by minimal number of complications and side reactions. At the same time, 5-year control of tumor growth for skull base meningioma was 96.8%, neuroma - 97%, glomus tumor - 94%, pituitary adenoma - 96-98%, craniopharyngioma - 95% in overall 10-year survival 86%, pilocytic astrocytoma - 97.5% in overall 5-year survival 99%. In intracranial metastases, median overall survival after radiosurgery was 10.1 months, 24- and 36-month overall survival - 25.9% and 19.2%, respectively. In patients with recurrent high-grade glioma, overall survival was 27.4 months. In case of metastatic spine lesions, control of tumor growth within 1 year was achieved in 90% of patients, pain relief - in more than 50% of cases. Obliteration of AVM and dural fistula was found in more than 80% of patients in years after treatment. Reduction or disappearance of pain was also observed in 80% of patients with trigeminal neuralgia. CONCLUSION: Stereotactic irradiation is effective and safe in patients with various pathologies of the central nervous system and characterized by high socio-economic indicators. Our own data indicate more significant role of stereotactic irradiation in the treatment of neurosurgical patients and make it possible to revise the existing treatment standards.

[Central neurocytomas: long-term treatment outcomes]. / Tsentral'nye neirotsitomy golovnogo mozga: otdalennye rezul'taty lecheniya.

Central neurocytoma is a rare benign brain tumor. These tumors may be giant and accompanied by compression of ventricular system and surrounding structures. Modern treatment of brain neurocytoma includes extended resection and restoration of normal CSF circulation. Surgical treatment does not often lead to total resection of these tumors. Redo resection was preferred in patients with tumor progression for a long time. In the last decade, various authors report stereotactic irradiation for continued tumor growth to ensure local growth control. This study was aimed at evaluation of postoperative outcomes in patients with brain neurocytomas, as well as treatment of tumor progression in long-term period. OBJECTIVE: To analyze recurrence-free survival in patients with brain neurocytomas, risk factors of recurrence-free survival, effectiveness of various treatments for tumor progression and delayed complications. MATERIAL AND METHODS: Long-term postoperative follow-up data of patients with brain neurocytomas are reported in the manuscript. We analyzed recurrence-free survival and risk factors of recurrence-free survival, treatment outcomes in patients with progression of brain neurocytomas, long-term complications and their prevention. RESULTS: Follow-up included 84 out of 115 patients with brain neurocytoma after surgical treatment in 2008-2017. Follow-up period ranged from 2 to 10 years (mean 6 years) after resection. Most patients had regression of neurological symptoms after surgery. Continued tumor growth within 12-96 months after surgery occurred in 26 (30.19%) out of 84 patients (19 cases after partial resection and 7 cases after total resection according to MRI data). Two-year recurrence-free survival was 94%, 5-year survival - 83%. Risk factors of continued tumor growth were resection quality and Ki-67 index. Redo resection was performed in 7 cases. Eleven patients underwent stereotactic irradiation for tumor progression. Indications for stereotactic irradiation of central neurocytoma are MR data on continued growth of lateral ventricle tumor without signs of ICH and CSF flow impairment. There were no cases of hemorrhage inside the residual tumor and CSF flow impairment in early postoperative period after redo resection. In all cases (n=11), stereotactic irradiation (mean follow-up 2.5 years) ensured satisfactory control of tumor growth with reduction of the neoplasm in 4 cases and no tumor growth in 7 cases. CONCLUSION: Resection of central neurocytoma ensures long-term recurrence-free period. The main causes of tumor recurrence are partial resection and high proliferative activity (Ki-67 index over 5%). Redo resection is advisable for tumor progression followed by CSF flow impairment. In case of continued growth of neurocytoma without signs of intracranial hypertension, stereotactic irradiation with various fractionation modes ensures effective and safe control of tumor growth.

[Radiosurgical hypophysectomy in cancer pain treatment. Literature review and clinical case]. / Radiokhirurgicheskaya gipofizektomiya v lechenii farmakorezistentnoi onkologicheskoi boli. Obzor literatury i opisanie klinicheskogo sluchaya.

Cancer pain is one of the main problem in modern medicine. According European Society for Medical Oncology data, cancer pain prevalence is 64% among patient with terminal stage of disease and in 46% standard pain therapy was ineffective. Radiosurgical hypophysectomy is one of the important and perspective method in cancer pain treatment. This method could be offered patient with chronic disease. According literature review, endocrinology complications were very rare and occurred 10 months after therapy. Value of analgesic effect was 70-90%. In some trials, procedure was effective not only nociceptive, but also in neuropathic pain. More trials require for determination of indications and mechanism of action. The case of successful relief of resistant pain in patient with pancreatic cancer by means of radiosurgical hypophysectomy is described.

[Glioblastomas in patients with medulloblastomas after combined treatment]. / Vozniknovenie glioblastom u patsientov s medulloblastomami posle provedeniya kombinirovannogo lecheniya.

Medulloblastoma (MB) is the most common brain malignancy in children occurring in the posterior cranial fossa. This tumor is characterized by high risk of metastasis along the CSF pathways. Significant progress in research of this tumor and appropriate treatment is associated with determining the various molecular categories of primary medulloblastomas. This analysis includes certain factors of cytogenetic and transcriptional proliferation. Modern treatment approaches for patients older than 3 years include advanced resection, craniospinal irradiation with a boost on the postoperative bed followed by platinum-based chemotherapy. Conventional radiotherapy including craniospinal irradiation results a significant number of complications. Morbidity rate is increased throughout long-term follow-up. Secondary tumors including glioblastomas are under special attention since their occurrence is associated with a fatal outcome. This may partially explaine the fact that chemotherapy without repeated morphological verification doesn't always ensure tumor growth control in patients with recurrent medulloblastomas. The authors consider irradiation-induced glioblastomas secondary to primarily verified medulloblastomas in patients who had previously undergone craniospinal irradiation as a component of combined treatment after tumor resection. It was found that the incidence of this phenomenon is significant and made up about 10% among patients with recurrent medulloblastomas. This value is significantly higher compared to previous data. The authors analyzed patterns of occurrence of irradiation-induced glioblastomas depending on the molecular genetic group and clinical characteristics of patients after primary surgery. Treatment outcomes were estimated too. It was concluded that morphological verification is necessary if long-term recurrence is diagnosed after combined treatment of medulloblastoma.