[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.

[Hypothalamic hamartoma microsurgical resection using transcallosal transforaminal approach]. / Mikrokhirurgicheskaya rezektsiya gipotalamicheskikh gamartom s transkalleznym transforaminal'nym dostupom.

OBJECTIVE: Transcallosal transseptal interforniceal approach is recognized as the most appropriate route to resect sessile hypothalamic hamartomas but individuals with obliterated cavum septi pellucidi may pose difficulties to access these lesions safely. MATERIAL AND METHODS: Six patients aged 8-34 years (med - 15.5) with the rather small (medial volume - 1.2 cm3) and in all but one cases the Delalande-Type II intraventricular sessile hamartomas and intractable epilepsy underwent surgery. The last patient had a rather larger lesion (Type III) encroaching both hypothalami and infundibulum. Cavum septi could not be distinguished on preop MRI in all cases. Lesions were removed via transcallosal transforaminal route using CUSA and foraminal walls dynamic retraction. In 4 cases the ipsilateral anterior septal vein was divided to expand the orifice of Monro foramen facilitating illumination and dissection. RESULTS: Early postop course was uneventful in all cases. Total or near total lesion removal was revealed on post-surgery images in cases with Type II hamartomas. No one of patients with ligated septal veins exhibited any signs of venous infarcts. Median known FU is 3 years (14 months - 5 years). Three patients were free of every seizure at the last check (50%). Two other patients nevertheless persisting mild recent memory deficit, were able to live independently and reported rare non-disabling events. AE-medication was discontinued in 2 patients, in other three cases it was tapered and simplified. CONCLUSION: In a subset of carefully selected patients with rather small Delalande-Type II sessile hypothalamic hamartomas in case of obliterated Cavum Septi Pellucidum the transcallosal transforaminal approach may be attempted in alternative to conventionally used transseptal interforniceal route with similar outcome and acceptable morbidity.

[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.

[Modern aspects of surgery for cushing's disease]. / Sovremennye aspekty khirurgicheskogo lecheniya bolezni Itsenko­Kushinga.

Cushing's disease is a severe neuroendocrine disorder caused by chronic hypersecretion of ACTH by pituitary adenoma (corticotropinoma). Surgical resection is a gold standard for this disease resulting stable remission in about 65-95% of cases. Despite benign nature of corticotropinoma, recurrence rate is still higher (25-35%) even in specialized neurosurgical centers. Modifications in surgical strategy can prolong recurrence-free period.

[Lesion of optic nerves and chiasm following bifocal germinoma recurrence]. / Porazhenie zritel'nykh nervov i khiazmy kak proyavlenie retsidiva bifokal'noi germinomy.

The authors report a patient with recurrent bifocal germinoma of the optical nerves and chiasm after previous combined treatment. The tumor resulted progressive visual acuity loss despite subsequent therapy (glucocorticoid therapy, chemo- and radiotherapy). Differential diagnosis between tumor progression and consequences of radiotherapy was complicated by MRI negative pattern. Subsequent development of the process, signs of anterior visual pathway damage and tumor spread throughout the ventricular system and subarachnoid spaces according to neuroimaging data indicated recurrence of disease.

[Stereotactic irradiation in the complex treatment of patients with intracranial pilocytic astrocytoma]. / Stereotaksicheskoe obluchenie v kompleksnom lechenii patsientov s intrakranial'nymi piloidnymi astrotsitomami.

Complex management of patients with intracranial pilocytic astrocytoma (PA) consists of surgical treatment, drug therapy (mainly in young children) and radiotherapy. For many years, radiotherapy (RT) has been a standard for residual tumors, recurrence or continued growth of PA. Currently, stereotactic radiosurgery and radiotherapy are preferred for PA, because these procedures are characterized by high conformity and selectivity, precise irradiation of tumor with minimal damage to surrounding intact tissues. Stereotaxic approach is very important since PAs are localized near functionally significant and radiosensitive brain structures in most cases. There is significant experience of single-center studies devoted to radiotherapy of patients with PA at the Department of Neuroradiosurgery of the Burdenko Neurosurgery Center. In this research, the authors analyzed the results of stereotactic irradiation of 430 patients with PA for the period from 2005 to 2018.

[Treatment outcomes in patients with central nervous system germinoma (neuro-ophthalmic aspects)]. / Rezul'taty kompleksnogo lecheniya bol'nykh s pervichnoi germinomoi TsNS (neirooftal'mologicheskie aspekty).

OBJECTIVE: The analyze the neuro-ophthalmic outcomes in patients with pineal and suprasellar germinoma after complex treatment. MATERIAL AND METHODS: There were 125 patients (88 males, 37 females) with primary CNS germinoma for the period 2008-2017. All patients were divided into 3 groups depending on the tumor localization: pineal area - 62 patients, suprasellar neoplasm - 38 patients, bifocal germinoma - 25 patients. Treatment was performed in accordance with the «Germinoma-2008¼ protocol. Tumors were histologically patients (partial - 32 cases, subtotal - 16 cases). Surgery was followed by postoperative chemotherapy and stereotactic radiotherapy. The results were evaluated by neuro-ophthalmological examination at all stages of complex treatment. RESULTS: Pineal germinoma resulted oculomotor and pupillary disorders (58 patients - 94%) and papilledema. The last one completely regressed under the treatment. Partial reduction of oculomotor and pupillary abnormalities occurred throughout chemotherapy (6 patients - 10%). More than half of patients (n=24, 63%) with suprasellar germinoma had visual impairment. Improvement of visual functions including severe visual disturbance was observed in 14 patients (58%). Predominantly, functional recovery occurred under chemotherapy (12 patients - 86%). Bifocal germinoma was followed by various combinations of oculomotor, pupillary and/or visual impairments. We observed regression of only mild visual disorders. Stereotactic radiotherapy did not ensure any changes in neuro-ophthalmic symptoms in all groups.

[Pseudoprogression of intracranial pilocytic astrocytomas and other low-grade gliomas. Literature review and case report]. / Psevdoprogressiya intrakranial'nykh piloidnykh astrotsitom i drugikh gliom nizkoi stepeni zlokachestvennosti. Obzor literatury, metaanaliz i klinicheskoe nablyudenie.

Tumor pseudoprogression is characterized by temporary tumor enlargement following radiotherapy with subsequent stabilization or regression without additional treatment. This phenomenon has been comprehensively described in patients with malignant gliomas. However, this phenomenon has not been sufficiently studied in patients with low-grade gliomas including pilocytic astrocytomas. In recent years, more and more researches devoted to this problem have appeared in the literature. It seems relevant to conduct a meta-analysis of these data in the modern literature.

[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.

[Use of chemotherapy in the treatment of aggresive pituitary adenomas]. / Khimioterapiia v lechenii agressivnykh adenom gipofiza.

AIM: To clarify the concept of 'aggressive pituitary adenoma' using analysis of the current concepts, as well as to determine the optimal treatment algorithm for this disease and the place of chemotherapy in this treatment. Pituitary adenomas comprise from 10 to 15% of intracranial neoplasms. Despite the fact that pituitary adenomas are benign neoplasms, in 25-55% of cases they demonstrate invasive growth, growing into the surrounding structures (sphenoid sinus, cavernous sinus, etc.). Due to the lack of a standard definition of aggressive pituitary adenomas (due to the lack of clear criteria for this disease), there are no studies in the literature reporting optimal treatment for this group of patients, except for several publications describing the use of Temozolomide as palliative therapy.

[Correct use of Kreatech DNA probes to detect MYC gene amplification in medulloblastomas by fluorescence in situ hybridization]. / Korrektnoe ispol'zovanie DNK-zondov Kreatech dlia vyiavleniia amplifikatsii gena MYC v medulloblastomakh metodom fliuorestsentnoi gibridizatsii in situ.

In most cases, oncogene amplification are prognostic and predictive markers for various tumors, therefore DNA probes are unable to reveal changes in the copy numbers should not be used to diagnose malignant tumors. OBJECTIVE: To comparatively analyze DNA probes from different manufacturers to detect MYC gene amplification in routine practice. MATERIAL AND METHODS: The study material was formalin-fixed paraffin-embedded medulloblastoma fragments from 4 patients, with discrepancies in the results in the detection of MYC gene amplification. RESULTS: MYC gene amplification was determined using DNA probes: Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG, and Zytolight SPEC MYC/CEN 8 Dual Color Probe. The use of the probes Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color probe failed to detect MYC gene amplification; this probe showed a balanced profile of chromosome 8. CONCLUSION: In routine practice, fluorescence in situ hybridization with the DNA probes Kreatech MYC (8q24)/SE 8, Vysis LSI MYC SO, Vysis CEP 8 (D8Z2) SG and Zytolight SPEC MYC/CEN 8 Dual Color Probe can be the method of choice for studying the copy number of the MYC gene. However, the authors strongly recommend that the Kreatech TERC (3q26)/MYC (8q24)/SE7 Triple-Color should not be used for this purpose. In addition, probes for fluorescence in situ hybridization must be necessarily tested in large reference laboratories dealing with one or another area of oncopathology.

[Radiotherapy and radiosurgery in treatment of craniopharyngiomas]. / Luchevaia terapiia i radiokhirurgiia v lechenii kraniofaringiom.

Craniopharyngiomas are benign epithelial tumors having a dysembryogenetic origin, which are usually located in the sellar/parasellar and/or third ventricle regions. Gross total resection is the modern standard of treatment for these tumors because of a low recurrence rate. However, this surgery in some patients with craniopharyngioma often leads to the development or worsening of diencephalic disorders poorly responding to treatment. Perhaps, in these cases, subtotal or partial tumor resection or implantation of an Ommaya reservoir into the tumor cyst followed by stereotactic radiotherapy/radiosurgery may provide better functional outcomes and higher life quality in patients, with tumor growth control being reasonable (according to the published data, the mean 10-year disease-free survival is 66.9% after total tumor resection and 79.6% after combined treatment). The paper presents a review of the literature on radiological treatment of craniopharyngiomas. We discuss the issues of indications, optimal timing of radiotherapy/radiosurgery, its efficacy, and treatment outcomes in terms of complications and quality of life. Particular attention is paid to enlargement of craniopharyngioma cysts during and after radiological treatment.

[Transient enlargement of craniopharyngioma cysts after stereotactic radiotherapy and radiosurgery]. / Tranzitornoe uvelichenie ob''ema kist kraniofaringiom posle stereotaksicheskoi luchevoi terapii i radiokhirurgii.

Stereotactic radiotherapy/radiosurgery (RT/ES) is an effective technique for treating craniopharyngiomas (CPs). However, enlargement of the cystic part of the tumor occurs in some cases after irradiation. The enlargement may be transient and not require treatment or be a true relapse requiring treatment. MATERIAL AND METHODS: In this study, we performed a retrospective analysis of 79 pediatric patients who underwent stereotactic RT or RS after resection of craniopharyngioma. RESULTS: Five-year relapse-free survival after complex treatment of CP was 86%. In the early period after irradiation, 3.5 months (2.7-9.4) on average, enlargement of the cystic component of the tumor was detected in 10 (12.7%) patients; in 9 (11.4%) of them, the enlargement was transient and did not require treatment; in one case, the patient underwent surgery due to reduced visual acuity. In 8 (10.1%) patients, an increase in the residual tumor (a solid component of the tumor in 2 cases and a cystic component of the tumor in 6 cases) occurred in the long-term period after irradiation - after 26.3 months (16.6-48.9) and did not decrease during follow-up in none of the cases, i.e. continued growth of the tumor was diagnosed. A statistical analysis revealed that differences in the terms of transient enlargement and true continued growth were statistically significant (p<0.01). CONCLUSION: Enlargement of a craniopharyngioma cyst in the early period (up to 1 year) after RT/RS is usually transient and does not require surgical treatment (except cases where worsening of neurological symptoms occurs, or occlusive hydrocephalus develops).

[Basal ganglia germinomas in children. Four clinical cases and a literature review].

UNLABELLED: Basal ganglia germinomas are a specific group of intracranial germinomas. Their early diagnosis is complicated due to their atypical localization and diversity of neuroimaging and clinical signs. MATERIAL AND METHODS: We describe 4 cases of basal ganglia germinoma in boys of 13, 14, 15, and 16 years of age. The medical history data, clinical features, neuroimaging and histological characteristics of basal ganglia germonomas, and preliminary results of the treatment are presented. CONCLUSION: Basal ganglia germinomas are usually verified at the late stage of the disease when patients are detected with extended lesions of the basal ganglia and severe neurological and neuroendocrine deficits. This situation is due to clinical and imaging signs that are untypical of common germinomas.

[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.

[Growing teratoma syndrome in a patient with intracranial germ cell tumor].

A six-year-old patient with non-germinomatous germ cell tumor of the chiasmatic-sellar area developed polyuria and polydipsia as the first symptoms of the disease. Then there were signs of precocious puberty and vision impairment. MRI examination revealed a shiasmatic sellar tumor and occlusive hydrocephalus. Tumor marker levels in blood serum were elevated. The alpha-fetoprotein level was increased 5-fold; human chorionic gonadotropin 20-fold. These levels increased over time. The patient received 2 cycles of PEI multiagent chemotherapy (Ifosfamide 1.5 g/m(2), Cisplatin 20 mg/m(2), Etoposide 100 mg/m(2)) during 5 days and 1 cycle of second-line multiagent chemotherapy (Cisplatin 100 mg/m(2) for 1 day and Endoxan 1500 mg/m(2) for 2 days). Despite the decrease in tumor marker levels to normal values, the patient's vision still deteriorated. MRI examination revealed that tumor size increased and its structure changed. Total tumor resection led to vision improvement and regression of intracranial hypertension. Histological analysis of tumor tissue only revealed a mature teratoma. This phenomenon, known as growing teratoma syndrome, is very rare among patients with intracranial non-germinomatous germ cell tumors.

[The outcomes of stereotactic radiotherapy in patients with cerebral arteriovenous malformations].

INTRODUCTION: Cerebral arteriovenous malformations (AVMs) are the congenital anomalies of development of cerebral vessels during the embryonic period. The conventional therapy for AVMs currently includes endovascular management, microneurosurgical resection, and stereotactic irradiation. MATERIAL AND METHODS: A total of 315 patients with brain AVMs were subjected to stereotactic radiotherapy in 2005-2011. 238 (76%) patients had previous subarachnoid hemorrhage (SAH) within different time (6 months to 5 years) before the therapy; 214 (68%) patients had headaches; 113 (36%) patients had focal neurological symptoms caused by localization; and 82 (26%) patients had seizures. Twenty-three patients were subjected to surgical resection of an intracerebral hematoma prior to radiotherapy and 119 (36%) patients received endovascular treatment including partial embolization of the stroma of AVM. 267 patients received single-fraction radiosurgical irradiation. In patients with large AVMs, we used the hypofractionation technique consisting in target irradiation with several (usually 2-7) fractions; the radiation dose per fraction exceeds 2 Gy. Forty-six patients were irradiated in the hypofractionation mode; two patients had a course of stereotactic radiotherapy in the standard fractionation mode. The marginal dose of radiosurgical irradiation was 13-30 Gy (the average dose was 24 Gy). The main group of patients (38 individuals) with large AVMs was treated using hypofractionation of 35 Gy per 5 fractions. RESULTS: Control angiography was carried out in 225 patients who had been followed up for at least 2 years after therapy showed that complete obliteration was achieved in 83% of cases. The rate of symptomatic radiation reactions was less than 10%. The higher risk of developing obliteration was observed for AVMs less than 2 cm3 in size at marginal doses more than 24 Gy. In the hypofractionation group consisting of 27 patients with complete follow-up data, obliteration was observed in 10 (37%) patients. The rate of symptomatic reactions was less than 35%. CONCLUSIONS: The radiosurgical method is a minimally invasive choice of treatment for patients with brain AVM, which allows one to achieve sufficiently high degree of obliteration with the minimum complication rate. The hypofractionation procedure is the method of choice for treating large AVMs. Stereotactic irradiation using the Novalis linear accelerator makes it possible to treat patients with AVMs of virtually any location and volume.