[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.

[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.

[Multicystic transformation of the post-radiation necrosis zone of the brain. A case report and literature review]. / Mul'tikistoznaya transformatsiya zony postluchevogo nekroza golovnogo mozga. Klinicheskoe nablyudenie i obzor literatury.

Post-radiation cyst of the brain is a rare complication that often arises many years after irradiation for head and neck neoplasms. The majority of the articles devoted to this problem are small samples or case reports. Nevertheless, the overall number of these patients is steadily increasing. The feature of post-radiation cysts is gradual enlargement followed by general cerebral and focal symptoms and ineffectiveness of therapy. Some patients with clinically significant post-radiation cysts can require surgical treatment. Insertion of Ommaya reservoir may be preferred in these patients. In some cases, this method is ineffective and more complex surgeries may be required. The objectives of this report were to analyze literature data and describe the patient with multiple recurrent brain cysts after previous irradiation for frontotemporal skin melanoma. Twenty-seven publications were analyzed for the period from 1997 to 2018. According to the literature, the incidence of post-radiation cysts varies from 0.4% to 28%, timing of occurrence - from 2 months to 27 years. These values significantly depend on the underlying disease. We report a 27-year-old patient who admitted to the Burdenko Neurosurgery Center with focal and general cerebral symptoms after irradiation for skin melanoma of the right frontotemporal region. These symptoms were caused by cystic lesion of the right temporal and frontal lobes. Surgical treatment consisted in insertion of 2 Ommaya reservoirs. This approach ensured complete regression of the cyst in the right temporal lobe and mild decrease of the cyst in the right frontal lobe.

[Multi-session stereotactic radiotherapy in the treatment of recurrent B-cell primary intraocular lymphoma (a case report)]. / Mnogokratnoe primenenie stereotaksicheskoi radioterapii dlia lecheniia retsidiviruiushchei V-kletochnoi pervichnoi intraokuliarnoi limfomy (klinicheskii sluchai).

The article describes the clinical observation of a 41-year-old woman suffering from non-Hodgkin's B-cell primary lymphoma of the central nervous system involving both eyes. The article features the data on 85-month follow-up, as well as description of the clinical and instrumental features of the disease. The study provides analysis of the long-term results of combined treatment of recurrent primary intraocular lymphoma including repeated courses of radiation therapy.

[A modern strategy of combined surgical and radiation treatment in patients with brain metastases]. / Sovremennaia strategiia kombinatsii khirurgicheskogo i luchevogo lecheniia u patsientov s metastazami v golovnom mozge.

The treatment standards for patients with brain metastases have been developed for several decades. An important element in the evolution of approaches to the treatment of these patients is the development of microsurgery, stereotactic radiotherapy, and targeted therapy and introduction of these techniques into clinical practice. Surgery is an effective treatment option in patients having single brain metastases and/or occuring in life-threatening clinical situations. Irradiation of the whole brain after surgical treatment is a necessary step in achieving satisfactory local control of intracranial metastatic foci, but the development of neurocognitive disorders and deterioration of life quality after this irradiation necessitate the search for alternative radiotherapy techniques in this clinical situation. Currently, an alternative to postoperative irradiation of the whole brain is stereotactic radiotherapy, which is used before or after surgical treatment. Stereotactic radiotherapy improves local control of intracranial metastatic foci and reduces the risk of neurotoxicity. In this review, we analyze the literature data on outcomes of stereotactic irradiation as a component of combined treatment of patients with metastatic brain lesions.

Kidney cancer with brain metastases. Prognostic factors and treatment outcome.

The aim of this study was to study the effectiveness of stereotactic radiosurgery by Gamma Knife in kidney cancer with brain metastases. There were analyzed results in 112 patients with such spread of the disease who received treatment in the Gamma Knife Center, Moscow. The median age of patients was 58 years (range, 33-77 years). Total number of metastatic lesions was 444, and the average number of brain metastases in one patient 4 (from 1 to 30). A single brain metastasis had 28 patients (25 %). Median of total volume of brain metastasis for each patient was 5. 9 cm3 (from 0. 1 to 29,1sm3). Mean marginal dose for metastatic lesion was 22 Gy (from 12 Gy to 26 Gy) and the average value of isodose, on which planning was performed - 64% (from 39% to 99%). The overall survival after radiosurgery was 37,7%, 16,4% and 9,3% for 12, 24 and 36 months, respectively, with a median overall survival of 9,1 months (95% CI = 7,1-11,8). New brain metastases after radiosurgical treatment occurred in 44 (54,3%) patients with a median of 10,1 months. (95% CI = 7-18). Local recurrences after radiosurgical treatment were detected in 19 (17%) patients with a median of 6,6 months (95% CI = 4,0-9,6). The Karnovsky index was >80. Local control was achieved in 96% of metastatic lesions in 87% of patients. Side effects of radiosurgical treatment occurred in 33. 8% of patients (6% radionecrosis and 23. 8% an increase of perifocal edema). Thus stereotactic radiosurgery by Gamma Knife is an effective treatment option for brain metastases in kidney cancer providing a high level of local control of metastatic lesions with minimal neurotoxicity. In a case of distant recurrence reuse of such treatment provides good local control and improves overall survival compared with other methods of treatment.

[Radiotherapy of primary intraocular lymphoma associated with primary central nervous system lymphoma]. / Radioterapiya pervichnykh intraokulyarnykh limfom, assotsiirovannykh s pervichnoi limfomoi tsentral'noi nervnoi sistemy.

AIM: The aim of the study was to define indications for stereotactic radiotherapy (SRT) of primary intraocular lymphoma (PIOL) and to evaluate the SRT efficacy and toxicity level. MATERIAL AND METHODS: Twelve immunocompetent patients with PIOL associated with primary CNS lymphoma underwent SRT of the affected eye/both eyes area. Three patients underwent repeated SRT due to PIOL recurrence. RESULTS: An improvement in visual acuity occurred in 6 patients. No changes in the visual function were observed in patients with high visual acuity, patients with amaurosis, and patients with concomitant eye diseases. Tumoral infiltration of the vitreous body resolved/decreased in all patients, except one case with retinal PIOL. PIOL recurrence developed in 6 patients. The disease-free period ranged from 1 to 24 months. The development/progression of cataract was found in 2 patients. Temporary radiation epidermitis occurred in 7 patients. Three patients developed ocular hypertension. One patient had lower eyelid ectropion. CONCLUSION: SRT is indicated for PIOL recurrence after intravitreal methotrexate injections, and in the case when local chemotherapy can not be used. In the case of combined injury to the brain and eyes, it is recommended that planned whole brain irradiation to involve the eyeball area. Local SRT is recommended if lymphoma locally affects the eye (or both eyes) without involvement of the brain. PIOL radiotherapy enables achieving persistent local disease control with minimal toxicity manifestations.

[Epidemiology, diagnosis, clinical symptoms, and classification of malignant primary skull base tumors]. / Épidemiologiia, diagnostika, klinicheskaia simptomatika i klassifikatsiia pervichnykh zlokachestvennykh opukholei, porazhaiushchikh osnovanie cherepa.

A review of literature presents up-to-date information on the prevalence, incidence, clinical manifestations, diagnosis, and classification of malignant primary skull base tumors (MPSBTs). In the structure of total cancer incidence, malignant head and neck tumors account for 5% of all annual cancer deaths in the USA and are among the 5 most common groups of tumors in males worldwide. These tumors develop most often in the sixth decade of life, occurring 2 times more often in males than in females. In Russia, the MPSBT incidence (as of 2012) was 0.62% out of all newly diagnosed malignant tumors. The incidence rate amounts to 0.66 per 100 000 population and is significantly higher than the global rate (0.44 per 100 000). About half of all malignant skull base tumors have the epithelial nature and affect the anterior parts of the skull base. The most frequent histological types of malignant skull base tumors are squamous cell carcinoma, adenocarcinoma, and non-Hodgkin's B cell lymphoma. Treatment of skull base tumors is an interdisciplinary problem and the area of interest of otolaryngologists, dentists, ophthalmologists, neurosurgeons, plastic surgeons, radiologists, and chemotherapists. Physical and endoscopic examinations, endoscopic transnasal biopsy, CT, MRI, PET/CT, and ultrasound are typically used for verification of the diagnosis, tumor staging, and selection of the treatment approach. The review describes the criteria for TNM staging of malignant tumors of the nasal cavity and paranasal sinuses in accordance with the 7th version of the TNM recommendations of the American Joint Committee on Cancer (AJCC). The TNM-based staging depends on the location (maxillary sinus, nasal cavity, or ethmoid labyrinth) and histological structure of the tumor, which, in turn, determines the tactics of comprehensive treatment and a prognosis group.

[Overall survival and intracranial relapse in patients with brain metastases after gamma knife radiosurgery alone].

UNLABELLED: The study purpose was to evaluate the impact of gamma knife radiosurgery (GKRS) alone on the overall survival and rate of intracranial recurrences in brain metastasis patients. MATERIAL AND METHODS: Treatment outcomes in 502 patients (211 males and 291 females with 2782 brain metastases (BMs)) were retrospectively reviewed. Most patients (n=142; 28.2%) were diagnosed with breast cancer. Multiple BMs were detected in 259 patients (51.6%). The median of the total tumor volume and ВM number was 5.9 cm3 (0.09-44.5 cm3) and 4 (1-36), respectively. The mean marginal radiation dose was 21 Gy (15-24 Gy). The mean follow-up period was 10.6 months (0.2-47.2 months). RESULTS: The overall survival rate for 12 and 24 months was 37.6 and 19.1%, respectively. The median overall survival after GKRS was 8.6 months (95% confidence interval (CI) 7.0-10.0). Local control of metastatic lesions was achieved in 78.8% of patients. The median local recurrence-free survival was 6.8 months after radiosurgery. The development of new (distant) metastases was observed in 49.5% of patients. The median distant metastasis-free time was 8.8 months. The Karnofsky performance score (KPS) of ≥80 (HR 0.3935, 95% CI 0.2429-0.6376; p=0.0002), BM number of <3 (HR 0.6138, 95% CI 0.3993-0.9943; p=0.0269), and BMs of breast and lung cancers (HR 0.5442, 95% CI 0.3642-0.8071; p=0.0027) are predictors of better survival. In the case of intracranial metastasis recurrence, repeated radiosurgery provides the median overall survival of 19.6 months versus 9.6 months in patients without radiosurgery (HR 0.4026, 95% CI 0.2381-0.6809). CONCLUSION: Radiosurgical treatment of patients with multiple BMs provides the median overall survival of 8.6 months. A good functional status, non-extensive metastasis of the brain, and radiosensitive morphology of the primary tumor are the predictors of better survival. Repeated radiosurgical treatment for intracranial recurrences provides longer overall survival compared to that in patients without repeated radiosurgical treatment.

[Metastatic brain lesion paradigm shift in radiation therapy].

The development of methods of treatment using radiosurgery devices "Gamma Knife", "Cyber Knife" has significantly changed the results of treatment of patients with brain metastases, which allowed formulating new principles of treatment of this group of patients. Radiosurgical treatment by means of "Gamma Knife" and "Cyber Knife" provides stable reproducible results with local tumor control in the case of both single and multiple lesions. The optimal minimum dose is 18Gy. Indicators of local control were 90-94% for brain metastases from breast cancer and 81-98% for brain metastases from lung cancer. With respect to radioresistant brain metastases local tumor control after radiosurgical treatment was 73-90% for patients with melanoma and 83%-96% for patients with renal cell carcinoma. Currently there is a tendency of application of radiosurgical treatment of patients with multiple brain mertastases. Numerous studies show a high rate of local tumor control after radiosurgical treatment in this patient group. This review summarizes current literature data on radiosurgical treatment for brain metastases with an emphasis on survival, local control, distant metastasis, quality of life as well as the potential combinations of existing treatment methods.

[Stereotactic radiotherapy for spinal meningiomas and neurinomas].

INTRODUCTION: Over the past decades, stereotactic conformal radiotherapy of intracranial meningiomas and schwannomas has been recognized as an effective and safe procedure. Due to the wide use of the CyberKnife system and the procedure of extracranial stereotactic radiotherapy and radiosurgery, the positive experience can be used to treat spinal tumors. This study assessed the effectiveness of stereotactic radiaotherapy of spinal meningiomas and neurinomas using the CyberKnife system. MATERIAL AND METHODS: 46 patients (34 females and 12 males) received treatment between November 2009 and December 2013 (65 tumor nodules). The median age of patients receiving radiotherapy was 49 years (range: 20 to 82 years). Twenty neoplasms were subjected to surgical treatment. In 11 patients, formation of the recurrent tumor foci following treatment was observed along with the systemic disease, neurofibromatosis. Six patients had multiple meningiomas. The median total dose of radiation therapy of neurinomas was 13.6 Gy (12.1-14.1 Gy) per fraction; up to 18.2 Gy (16.0-21.1 Gy) per three fractions; and up to 25.6 Gy (24.8-27.6 Gy) per five fractions. Higher doses were used for meningiomas: 15.9 Gy (14.1-16.2 Gy) per fraction; 20.9 Gy (19.5-21.1 Gy) per three fractions; and 27.5 Gy (25.0-29.9 Gy) per five fractions. The load to 0.15 cm3 of the spinal cord was no higher than the maximum permissible load of 12 Gy per fraction. The mean catamnestic follow-up was 18.1 (4-52) months: 21,1 (4-52) months for neurinomas and 18 (4-31) months for meningiomas. We have not observed complete tumor elimination (i.e., complete response to radiation therapy) in our series. Partial response was observed in 9 (13.8%) cases; stabilization was achieved in 54 (83.1%) cases; and tumor continued to grow in 2 (3.1%) cases. The patients' status was evaluated using the Frankel, the Karnofsky, and the VAS scales. CONCLUSIONS: Our findings clearly demonstrate the short-term benefits of using CyberKnife radiotherapy for benign spinal cord tumors. The catamnestic follow-up needs to be extended to elaborate recommendations for radiation. The progress in this therapy type will considerably improve the quality of medical care provided to this cohort of patients.

[Rare case of vitreoretinal lymphoma].

Primary intraocular lymphoma (PIOL) is a primary central nervous system lymphoma subtype. The article presents a case of bilateral vitreoretinal lymphoma in a functionally monocular 68-year-old woman, whose ocular manifestations developed prior to multiple primary lymphoma of the brain, thus, impeding the diagnosis. Stereotactic radiotherapy enabled stabilization of the process and did not affect visual functions.

[Breast carcinoma metastasis to the optic nerve: case report and review of literature].

Metastatic tumours of the optic nerve are extremely rare. The review of literature revealed only 12 cases of breast carcinoma metastasis to the optic nerve. All patients survived less then 6 month after surgical treatment. We describe a case of metastatic breast carcinoma to the optic nerve that occurred 8 years after radical mastectomy followed by chemotherapy. The metastasis manifested with progressive decrease in visual acuity in the right eye during 3 month. CT and MRI demostrated enhancing lesion in the muscle cone apex of the right orbit with an extension to the optic canal. The presumable diagnosis was optic nerve sheath meningioma, and surgical resection was performed. The tumour involved the optic nerve and has been resected togeher with the nerve. Histology report confirmed metastatic tumour. Postoperatively, the patient received additional stereotactic radiotherapy. Patient died of tumour dissemination 2,5 years after surgery. Breast carcinoma metastases to the optic nerve usually have unfavorable prognosis both for survival and for visual acuity. Isolated metastatic tumors of the optic nerve remain a diagnostic challenge because of their clinical and radiological similarities to more common primary tumors of the optic nerve.

[Primary and metastatic Ewing sarcoma of the skull base - case reports and comparative analysis].

UNLABELLED: The aim of the present study was to evaluate and compare diagnostic/and treatment modalities of primary and metastatic Ewing sarcoma (ES) of the skull base. MATERIAL AND METHODS: We analyzed nine cases of the skull base ES patients operated in Burdenko Neurosurgical Institute from 2003 to 2011. Among them there were five cases of primary ES, the other four were of metastatic origin. Clinical history, neuroimaging and pathology data together with IHC are presented. Treatment options and results are discussed. Seven patients were operated transcranially, in the other two cases endoscopic endonsnasal operations/were performed. Mean follow up was 11-92 months. RESULTS: We did not reveal arW pathological or IHC differences between primary and metastatic tumors. The labeling index Ki-67 was insignificantly higher in the metastatic tumors gro'Vip. In one case the patient developed relapse of the metastatic tumour in the temporal bone; he underwent second surgery and died 7 months after the operation. CONCLUSION: Despite both metastatic and primary ES of the skull base are of maMignant behavior, the long-term relatively good prognosis can be achieved when combined treatment, including surgery, chemotherapy and radiation is applied.

[Stereotactic radiotherapy for cerebral metastases using CyberKnife].

During recent decade development of frameless techniques of fixation enabled introduction of stereotactic radiation therapy in metastatic brain lesions and made possible irradiation of large foci involving or proximal to eloquent and critical brain areas. This paper focuses on comparative analysis of effectiveness of hypofractionation (HRST) and radiosurgery (SRS) using CyberKnife system in cerebral metastases. Since November 2009 till June 2011 54 patients with cerebral metastases were treated using CyberKnife system. Age of patients ranged between 25 and 77 years (mean 54 years). 16 patients received radiosurgical treatment (mean total dose was 22.5-35 Gy, number of fractions varied from 2 to 7, mean volume of irradiation was 22.69 cm3) and 8 patients were treated by HRST with RS of selected foci (mean total dose reached 23 and 30 Gy, mean volume of irradiation was 1.02 cm3 and 11.19 cm3, respectively). Indices of overall regression and stabilization of disease for HRST and SRS groups were 81% and 79%, respectively. With mean follow-up period of 12.3 (1-16.1) months median survival for SRS and HRST reached 6.38 (1-15.8) and 6.2 (0.2-16.1) months and median recurrence-free survival was 3.6 (1-13.6) and 5.5 (2-14.2) months, respectively. Obtained results confirmed biological advantages of fractionated stereotactic radiotherapy of large cerebral tumors in comparison with radiosurgery. Prospective studies with rigid criteria of inclusion are required to determine optimal dose/volume/fractionation interrelations in stereotactic radiation treatment of cerebral metastases.

[CyberKnife stereotactic radiotherapy for mass lesions of the spinal cord and spine].

Introduction of a novel technology of stereotactic radiation treatment using linear accelerators, refining of systems for visualization and guidance provided rapid development of extracranial radiosurgery. Nowadays there is a possibility of precise stereotactic irradiation of lesions with different size and localization. One of the most actual and promising indications for radiosurgery are different primary and metastatic lesions and arteriovenous malformations of spinal cord and spine. Radiosurgery and hypofractionated radiotherapy with precise dose delivery during one or several sessions allow effective and safe treatment of neoplasms with any degree of radioresistance. This paper contains analysis of the first Russian experience of stereotactic radiation treatment of lesions of spinal cord and spine using robotized system CyberKnife (Accuray Inc., USA).

[Application of robotized radiosurgical system CyberKnife for the treatment of neurosurgical patients].

Robotized system for radiosurgery CyberKnife (Accuray Inc., USA) is the first device dedicated and optimized for advanced irradiation during 1-7 fractions (i.e. radiosurgery and hypofractionation). CyberKnife is characterized by elaborate guidance system, high precision of dose delivery, possibility of conformal dose distributions with high gradient of target borderline dose which is most important in proximity of critical structures. The first CyberKnife system in Russia was installed in Burdenko Neurosurgery Institute. The paper presents 2-year experience of treating patients using CyberKnife. From April 2009 till October 2011 896 patients were treated using CyberKnife. Mean age was 48 years. Overall number of sessions was 2626. Radiosurgical procedures were performed in 21.8% of patients. 91% of cases were treated for intracranial lesions. Limited follow-up period in all kinds of pathology demonstrated results consistent with standard fractionation or radiosurgery. The rates of observed complications were also comparable with accepted techniques. CyberKnife system plays significant role in everyday activity of department of radiation therapy. In careful and thorough selection of patients it allows efficient and high-quality treatment of patients with neurosurgical diseases.