[Proton three-demensional conformal radiosurgery of arteriovenous malformation of the brain].

The proton beam radiosurgery was performed to 65 patients with brain AVM since December, 2001 till February, 2012, in Joint Institute for Nuclear Research, Dubna, Russia. We have analyzed data for 56 patients. The follow up time varied from 24 to 109 months. The volumes of brain AVMs varied from 0.92 to 82 cc. The mean isocenter dose was 24.61 +/- 0.12 Gy E. The edge of the target was included in 70-90% isodose. The proton beam surgery was splitted in two similar doses and delivered in two consecutive days in vast majority of patients. Ten patients were missed for follow up due to some reasons. The radiosurgery was resulted in full obliteration of AVM in 23 from remaining 46 (50%) patients. There was full obliteration in 46.6% of patients with volume of AVM 10-24.9 cc; and this rate is significantly more than for photon radiosurgery of same size brain AVM. The partial obliteration was obtained in 21 patients. Only one patients suffered hemorrhage from partially obliterated AVM. We could not see any effect in 2 patients. There were delayed radiation toxicity in 5 patients in 12 months after treatment: in 4 patients, these reactions were assessed as 2 according to RTOG scale and were dissipated in 1 month after commencement of corticosteroid treatment. There was radiation necrosis in one patient, and it was relieved in 12 months after several courses of dehydration and corticosteroid therapy. So, proton beam therapy is effective and safe modality for treatment of inoperable brain AVM, especially of middle- and large size.

[Significant regression of glioblastoma with low level of Mgmt gene expression following radiotherapy].

Radiochemotherapy is leading the universal research effort in fighting lethality: it is improving relapse-free survival of patients with inoperable glioblastoma, the most pernicious brain tumor in adults. Its effectiveness was found to depend on expression of Mgmt gene of tumor DNA reparation following radiochemotherapy and adequate medication based on the molecular phenotype of tumor. Our study involved a 40-year old male with a low level of Mgmt gene expression as established by stereotactic biopsy. The patient received hypofractionated three-dimensional conformational proton therapy with the benefit of temozolomide (140 mg/24 hr). Subsequently, the dose was raised to 360 mg/24 hr, on days 1-5 of the cycle. Contrast-enhanced MRI examination established significant diminishing of the size of tumors on completion of cycles 7 and 8; patients felt better, memory and blood indices improved. As of the time this paper was written, relapse-free survival was 17.5 months, as compared with the literature data on inoperable glioblastoma--5.5 months.

[Proton "radiosurgery" of cerebral arteriovenous malformations].

Arteriovenous malformations (AVM) are vascular lesions arising from impaired angiogenesis at the stage of transformation of primary embryonic arteriovenous anastomoses into capillaries. Commonly AVMs manifest with spontaneous hemorrhage. Stereotactic radiosurgery is method of choice for treatment of surgically inaccessible AVMs, which are characterized by high risk of damage of adjacent critical structures. In addition, stereotactic radiosurgery is used either as a component of complex management of large AVMs or pre-planned procedure combined with endovascular intervention, or as a second line therapeutic option in residual AVM after subtotal surgical resection. Comparing with photons protons due to their unique physical properties have advantages in spatial spread of dose thus allowing to significantly decrease integral dose to the surrounding brain tissue when treating large AVMs with complex shape proximal to critical structures.

[The role of radiation therapy in treating hypophyseal adenomas]. / Mesto luchevoi terapii v lechenii adenom gipofiza.

The article reviews various methods for the exposure of pituitary adenomas to the effect of radiation applied either as the only measure or in combination with surgery and drug therapy. The indications for radiotherapy are discussed according to the size and hormonal activity of the tumor.

[Proton therapy in clinical neurosurgery]. / Protonnaia terapiia v neirokhirurgicheskoi klinike.

The use of proton beam irradiation in neurosurgical clinical practice helps to find a solution to the problem of the treatment of inoperable malformations employing this method in some cases as an alternative to surgical intervention. Hypophyseal tumors, tumors of the cavernous sinus, arteriosinusal anastomoses in the cavernous sinus area, and arteriovenous malformations are irradiated at the N. N. Burdenko Institute of Neurosurgery, USSR, AMS using the medical proton beam of the Institute of Theoretical and Experimental Physics. Methods of "piercing" irradiation and methods with the use of Bragg's peak are being developed. At present over 200 patients with hormonally active hypophyseal tumors, 30 patients with tumors of the cavernous sinus, 23 patients with deep seated arteriovenous malformations, and 10 patients with spontaneous arteriosinusal anastomoses in the cavernous sinus area have been irradiated. This method seems to hold promise in neurosurgical practice. Extension of the range of clinical applications of proton beam therapy in neurosurgery requires the development of various techniques of irradiation, all possible approaches to various targets on the basis of contemporary methods of computerized diagnosis, topometry and irradiation design.

[Effect of proton irradiation of Tolosa-Hunt syndrome]. / Effekt protonnogo oblucheniia pri sindrome Tolosy-Khanta.

The authors have analysed a case of Tolosa-Hunt syndrome with a persistent recurring course and a gradual development of resistance to steroid therapy. Computerized tomography revealed a high density zone in the affected cavernous sinus of the patient. Differential diagnosis between a tumor and Tolosa-Hunt syndrome was made. The patient received 3 fractions of proton beam irradiation by the "piercing" method (the beam being 15 mm in diameter) at a dose of 60 Gy. After irradiation computerized tomography showed complete recovery of disturbed functions and disappearance of the focus. Four-year remission was observed. In our experience, it was the first case of the use of radiation therapy in Tolosa-Hunt syndrome.

[Proton irradiation of spontaneous arterio-sinus anastomoses in the cavernous sinus region]. / Protonnoe obluchenie spontannykh arteriosinusnykh soustii oblasti kavernoznogo sinusa.

Altogether 10 patients with spontaneous arteriosinusal anastomoses in the cavernous sinus area have been irradiated at the N. N. Burdenko Institute of Neurosurgery, USSR AMS. since 1983 using the synchrotron of the Institute of Theoretical and Experimental Physics. A "piercing" method with a proton beam of 12 mm in diameter (in one case 10 mm) was employed. Nine patients had unilateral anastomoses with the blood supply from branches of the internal and/or external carotid arteries, and one patient had a bilateral anastomosis. Irradiation was given in 2 fractions, in 2-3 days, the maximum total dose was 50-60 Gy. Regression of ophthalmological symptoms was noted 2-3 months after irradiation. Convalescence was noted in 8 patients, a follow-up period in 2 patients was insufficient. Of 7 patients examined by angiography complete thrombosis of the anastomosis was noted in 4, considerable reduction of the blood flow was noted in 3.

[Pre-radiation care in proton irradiation of tumors of the cavernous sinus]. / Predluchevaia podgotovka pri protonnom obluchenii opukholei kavernoznogo sinusa.

The authors described methods of the individual precision anatomodosimetric planning of proton-beam irradiation of tumors of the cavernous sinus. The results of computerized tomography in 2 planes (axial and frontal) were used for planning. Manual tumor reconstruction with subsequent dose planning was done on direct and lateral telecraniograms. The procedure was tested in 25 patients. Complications and noticeable radiation reactions in adjacent tissues were undetectable during 3.5 yrs.