Antifibrinolytic therapy of experimentally grown malignant brain tumors

1986 ◽  
Vol 64 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Raymond Sawaya ◽  
Thaddeus Mandybur ◽  
Illona Ormsby ◽  
John M. Tew
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
Tumor Volume ◽  
Malignant Gliomas ◽  
Fibrinolytic System ◽  
Survival Times ◽  
Content Type ◽  
Antifibrinolytic Therapy ◽  
Group A ◽  
Fine Print

✓ This study was designed to evaluate the effect of an inhibitor of plasminogen activation on the growth of a human glioblastoma line grown in nude mice up to the seventh passage. The tumors produced plasminogen activators and showed histological characteristics similar to those of the original tumor. Three groups of mice were studied. Group A received 5% epsilon aminocaproic acid (EACA); Group B received 2.5% EACA; and Group C served as a control. There was no statistical difference among the three groups with regard to: 1) age at time of tumor transplantation; 2) the interval between implant and treatment; or 3) tumor volume at time of treatment. Blood measurements of EACA, performed in a limited number of animals, have shown that the drug at 5% concentration had reached toxic levels. Statistically significant differences between the three groups were noted in the following categories: 1) rate of tumor growth; 2) tumor volume at time of death, where Group A had smaller tumors than Group C; and 3) mean survival times of Groups A and B as compared to Group C. A statistically significant negative correlation was found between the rate of tumor growth and the length of survival of animals in Group C, while no correlation could be found for either Group A or B, indicating that the antifibrinolytic therapy modified this important biological variable. This study supports the hypothesis that the fibrinolytic system plays a role in the growth and development of malignant gliomas and that interference with the fibrinolytic system may retard the growth of these tumors grown in nude mice.

Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice

1994 ◽  
Vol 80 (3) ◽  
pp. 520-526 ◽  
Author(s):  
Douglas W. Laske ◽  
Orhan Ilercil ◽  
Aytac Akbasak ◽  
Richard J. Youle ◽  
Edward H. Oldfield
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
Dose Response ◽  
Tumor Volume ◽  
Human Gliomas ◽  
Content Type ◽  
Protein Toxins ◽  
Fine Print ◽  
Intratumoral Injections

✓ Targeted protein toxins are a new class of reagents with the potential for great tumor selectivity and cytotoxic potency. Two such compounds were studied: 1) Tf-CRM107, a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107); and 2) 454A12-rRA, a conjugate of a monoclonal antibody (454A12) to the human Tf receptor and recombinant ricin A chain (rRA). Both compounds are potent and specific in killing human glioblastoma cell lines in vitro. The authors investigated the activity of these reagents administered intratumorally against solid U251 MG human gliomas in vivo. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were randomly assigned to be treated with 100-µl intratumoral injections of Tf-CRM107 (10 µg) or 454A12-rRA (10 µg), equimolar doses of CRM107 (4.3 µg), 454A12 antibody (7.5 µg), or rRA (1.5 µg), or phosphate-buffered saline (PBS) every 2 days for a total of four doses. Tumor volume and animal weight were assessed by a blinded observer before each treatment and biweekly for 30 days after initiating therapy. With Tf-CRM107 administration, tumor regression of greater than 95% occurred by Day 14 (p < 0.01) and tumors did not recur by Day 30. Treatment with 454A12-rRA caused a 30% decrease in tumor volume by Day 14 (p < 0.01). Treatment with equimolar doses of the unconjugated targeted protein toxin components CRM107, 454A12, or rRA caused significant U251 MG tumor growth inhibition, but the effects were less potent than the antitumor effects of the conjugates. This study also characterized the dose-response effect of Tf-CRM107 on tumor growth and tumor weight on Day 30. Nude mice with established U251 MG flank tumors (0.5 to 1.0 cm in diameter) were treated with 100-µl intratumoral injections of 10, 1.0, or 0.1 µg of Tf-CRM107 or PBS every 2 days for a total of four doses. All three doses of Tf-CRM107 significantly inhibited tumor growth by Day 14 (p < 0.01) and at Day 30 (p < 0.05), with a significant dose-response relationship. This study demonstrated in vivo efficacy of the targeted toxins Tf-CRM107 and 454A12-rRA against a human glioma. With intratumoral administration, the effect of Tf-CRM107 was tumor-specific and in some animals curative. Regional therapy with these potent tumor-specific agents using direct intratumoral infusion should limit systemic toxicity and may be efficacious against brain tumors.

Effect of the antiprogesterone RU-38486 on meningioma implanted into nude mice

1987 ◽  
Vol 66 (4) ◽  
pp. 584-587 ◽  
Author(s):  
Jeffrey J. Olson ◽  
David W. Beck ◽  
Janet A. Schlechte ◽  
Pao-Min Loh
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
Binding Proteins ◽  
Tumor Volume ◽  
Growth Index ◽  
Control Group ◽  
Content Type ◽  
Treatment Groups ◽  
Steroid Binding Proteins

✓ Meningiomas have been shown to have steroid-binding proteins. In vitro, estradiol, progesterone, and the antiestrogen tamoxifen stimulate tumor growth. However, incubation of tumor cells with an antiprogesterone agent results in tumor inhibition. In this investigation, a human meningioma was implanted subcutaneously in athymic nude mice. Two treatment groups were established, one receiving the antiprogesterone agent RU-38486 (10 mg/kg/day in suspension) and the other receiving only vehicle. After 3 months, the tumor growth index (defined as the tumor volume at 3 months divided by the initial tumor volume) was 0.25 ± 0.46 (mean ± standard deviation) in the group receiving antiprogesterone and was 1.54 ± 0.58 in the control group (p = 0.041). Further investigation of the effect of antiprogestational agents on the growth and hormone-binding proteins of other meningiomas will better define the mechanism of their effects.

Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages

2005 ◽  
Vol 103 (6) ◽  
pp. 1000-1009 ◽  
Author(s):  
Shin-Ichi Miyatake ◽  
Shinji Kawabata ◽  
Yoshinaga Kajimoto ◽  
Atsushi Aoki ◽  
Kunio Yokoyama ◽  
...  
Keyword(s):  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Tumor Volume ◽  
Malignant Gliomas ◽  
Neutron Capture Therapy ◽  
Boron Compounds ◽  
Content Type ◽  
Boron Neutron Capture ◽  
Fine Print

Object. To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds—sodium borocaptate (BSH) and boronophenylalanine (BPA)—with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. Methods. Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4–71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3–87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. Conclusions. This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

Combined inhibition of vascular endothelial growth factor and platelet-derived growth factor signaling: effects on the angiogenesis, microcirculation, and growth of orthotopic malignant gliomas

2005 ◽  
Vol 102 (2) ◽  
pp. 363-370 ◽  
Author(s):  
Mohammad Reza Farhadi ◽  
Hans Holger Capelle ◽  
Ralf Erber ◽  
Axel Ullrich ◽  
Peter Vajkoczy
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Malignant Gliomas ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Vascular Endothelial ◽  
Tumor Implantation ◽  
Content Type ◽  
Endothelial Growth Factor ◽  
Fine Print

Object. The goal of this study was to determine the effects of SU6668, a polyvalent receptor tyrosine kinase inhibitor against vascular endothelial growth factor receptor—2, platelet-derived growth factor receptor—β, and fibroblast growth factor—1 on tumor growth, angiogenesis, and microcirculation in an orthotopic malignant glioma model. Methods. Fluorescently labeled C6 malignant glioma cells were implanted into a long-term cranial window, which had been prepared in nude mice. The animals were treated with intraperitoneal injections of SU6668 (75 mg/kg/day) immediately (five animals) or 7 days (five animals) following tumor implantation. Control mice received intraperitoneal injections of vehicle (50 µl dimethylsulfoxide) immediately (five animals) or 7 days (four animals) after tumor implantation. Tumor growth, angiogenesis, and microcirculation were assessed by performing intravital fluorescence videomicroscopy over a 14-day observation period. To assess the effects of SU6668 on overall survival, C6 glioma cells were implanted stereotactically into the brains of 24 additional animals and treatment was initiated on Day 7. In both the immediate and delayed experimental setting, SU6668 treatment resulted in a significant reduction of total and functional tumor vessel densities (both p < 0.05), reflecting a suppression of angiogenesis and impairment of tumor perfusion. As a consequence, tumor growth was significantly inhibited (p < 0.05). Histological analysis demonstrated reduced tumor growth and less mass effect on the adjacent brain of treated animals. The survival experiments confirmed the importance of our results in that survival was significantly prolonged following SU6668 therapy (p < 0.05). Conclusions. Targeting of multiple angiogenic signaling pathways by polyvalent tyrosine kinase inhibitors represents a promising strategy to interfere with the vascularization, microcirculation, and growth of angiogenesis-dependent tumors. This also applies to malignant gliomas, despite the uniqueness of the cerebral microenvironment and the singular pathobiology of this tumor entity.

Effects of ACNU and radiotherapy on malignant glioma

1986 ◽  
Vol 64 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Kintomo Takakura ◽  
Hiroshi Abe ◽  
Ryuichi Tanaka ◽  
Koichi Kitamura ◽  
Tetsuro Miwa ◽  
...  
Keyword(s):  
Tumor Size ◽  
Performance Status ◽  
Malignant Gliomas ◽  
Hematological Toxicity ◽  
Survival Times ◽  
Chemotherapeutic Regimen ◽  
Content Type ◽  
Randomized Clinical Study ◽  
Radiotherapy Alone ◽  
Fine Print

✓ A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Combined cimetidine and temozolomide, compared with temozolomide alone: significant increases in survival in nude mice bearing U373 human glioblastoma multiforme orthotopic xenografts

2005 ◽  
Vol 102 (4) ◽  
pp. 706-714 ◽  
Author(s):  
Florence Lefranc ◽  
Syril James ◽  
Isabelle Camby ◽  
Jean-François Gaussin ◽  
Francis Darro ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Cells ◽  
Nude Mice ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Computer Assisted ◽  
Human Glioblastoma ◽  
Content Type ◽  
Human Glioblastoma Multiforme ◽  
Fine Print

Object. Malignant gliomas consist of both heterogeneous proliferating and migrating cell subpopulations, with migrating glioma cells exhibiting less sensitivity to antiproliferative or proapoptotic drugs than proliferative cells. Therefore, the authors combined cimetidine, an antiinflammatory agent already proven to act against migrating epithelial cancer cells, with temozolomide to determine whether the combination induces antitumor activities in experimental orthotopic human gliomas compared with the effects of temozolomide alone. Methods. Cimetidine added to temozolomide compared with temozolomide alone induced survival benefits in nude mice with U373 human glioblastoma multiforme (GBM) cells orthotopically xenografted in the brain. Computer-assisted phase-contrast microscopy analyses of 9L rat and U373 human GBM cells showed that cimetidine significantly decreased the migration levels of these tumor cells in vitro at concentrations at which tumor growth levels were not modified (as revealed on monotetrazolium colorimetric assay). Computer-assisted microscope analyses of neoglycoconjugate-based glycohistochemical staining profiles of 9L gliosarcomas grown in vivo revealed that cimetidine significantly decreased expression levels of endogenous receptors for fucose and, to a lesser extent, for N-acetyl-lactosamine moieties. Endogenous receptors of this specificity are known to play important roles in adhesion and migration processes of brain tumor cells. Conclusions. Cimetidine, acting as an antiadhesive and therefore an antimigratory agent for glioma cells, could be added in complement to the cytotoxic temozolomide compound to combat both migrating and proliferating cells in GBM.

The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice

1993 ◽  
Vol 78 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Mark E. Linskey ◽  
A. Julio Martinez ◽  
Douglas Kondziolka ◽  
John C. Flickinger ◽  
Ann H. Maitz ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Nude Mice ◽  
Time Course ◽  
Tumor Volume ◽  
Tumor Diameter ◽  
Vascular Effects ◽  
Content Type ◽  
Subrenal Capsule ◽  
Fine Print

✓ An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent “sham radiosurgery.” All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

Gamma knife radiosurgery in the management of cavernous sinus meningiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 68-73 ◽  
Author(s):  
Pierre-Hugues Roche ◽  
Jean Régis ◽  
Henry Dufour ◽  
Henri-Dominique Fournier ◽  
Christine Delsanti ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tumor Growth ◽  
Gamma Knife ◽  
Cavernous Sinus ◽  
Gamma Knife Radiosurgery ◽  
Surgical Removal ◽  
Content Type ◽  
Cavernous Sinus Meningioma ◽  
The Mean ◽  
Fine Print

Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6–71 years). The mean tumor volume was 5.8 cm3 (range 0.9–18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12–50 Gy), delivered with an average of eight isocenters (range two–18). The median peripheral isodose was 50% (range 30–70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12–79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity—related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

Gamma knife radiosurgery for craniopharyngiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 47-56 ◽  
Author(s):  
Wen-Yuh Chung ◽  
David Hung-Chi Pan ◽  
Cheng-Ying Shiau ◽  
Wan-Yuo Guo ◽  
Ling-Wei Wang
Keyword(s):  
Clinical Outcome ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Content Type ◽  
Stereotactic Aspiration ◽  
Cystic Component ◽  
The Mean ◽  
Fine Print

Object. The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999. Methods. There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3–69 years). The mean tumor volume was 9 cm3 (range 0.3–28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality. Conclusions. Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

Gamma knife surgery for vestibular schwannoma: 10-year experience of 195 cases

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 87-97 ◽  
Author(s):  
Wen-Yuh Chung ◽  
Kang-Du Liu ◽  
Cheng-Ying Shiau ◽  
Hsiu-Mei Wu ◽  
Ling-Wei Wang ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Gamma Knife ◽  
Vestibular Schwannoma ◽  
Tumor Volume ◽  
Radiation Effect ◽  
Gamma Knife Surgery ◽  
Homogeneous Distribution ◽  
Content Type ◽  
Fine Print

Object. The authors conducted a study to determine the optimal radiation dose for vestibular schwannoma (VS) and to examine the histopathology in cases of treatment failure for better understanding of the effects of irradiation. Methods. A retrospective study was performed of 195 patients with VS; there were 113 female and 82 male patients whose mean age was 51 years (range 11–82 years). Seventy-two patients (37%) had undergone partial or total excision of their tumor prior to gamma knife surgery (GKS). The mean tumor volume was 4.1 cm3 (range 0.04–23.1 cm3). Multiisocenter dose planning placed a prescription dose of 11 to 18.2 Gy on the 50 to 94% isodose located at the tumor margin. Clinical and magnetic resonance (MR) imaging follow-up evaluations were performed every 6 months. A loss of central enhancement was demonstrated on MR imaging in 69.5% of the patients. At the latest MR imaging assessment decreased or stable tumor volume was demonstrated in 93.6% of the patients. During a median follow-up period of 31 months resection was avoided in 96.8% of cases. Uncontrolled tumor swelling was noted in five patients at 3.5, 17, 24, 33, and 62 months after GKS, respectively. Twelve of 20 patients retained serviceable hearing. Two patients experienced a temporary facial palsy. Two patients developed a new trigeminal neuralgia. There was no treatment-related death. Histopathological examination of specimens in three cases (one at 62 months after GKS) revealed a long-lasting radiation effect on vessels inside the tumor. Conclusions. Radiosurgery had a long-term radiation effect on VSs for up to 5 years. A margin 12-Gy dose with homogeneous distribution is effective in preventing tumor progression, while posing no serious threat to normal cranial nerve function.

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