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BackgroundGamma Knife radiosurgery (GKRS) in the treatment of arteriovenous malformations (AVMs) is still controversially discussed.ObjectiveTo present long-term follow-up data on patients after Gamma Knife radiosurgery for cerebral AVMs.MethodsOverall, 516 patients received radiosurgery for cerebral AVMs between 1992 and 2018 at our department, of whom 265 received radiosurgery alone and 207 were treated with a combined endovascular-radiosurgical approach. Moreover, 45 patients were treated with a volume-staged approach. Two eras were analyzed, the pre-modern era between 1992 and 2002 and the modern era thereafter.ResultsIn GKRS-only treated patients, median time to nidus occlusion was 3.8 years. Spetzler–Ponce (SP) class was a significant predictor for time to obliteration in the whole sample. Median time to obliteration for the combined treatment group was 6.5 years. Patients in the pre-modern era had a significantly higher obliteration rate than those treated in the modern era. Overall, the calculated yearly hemorrhage risk in the observation period after first GKRS was 1.3%. Permanent post-radiosurgical complications occurred in 4.9% of cases but did not differ between the treatment groups or treatment eras. The obliteration rate was significantly lower and the hemorrhage rate was higher in volume-staged treated patients than in conventionally treated patients.ConclusionGKRS is an effective treatment option for SP class A and B cerebral AVMs. After combined endovascular-radiosurgical treatment, the outcome of selected SP class C AVMs aligns with that of SP class B lesions. Both the combined therapy and radiosurgery alone constitute sound methods for treatment of cerebral AVMs.

Objectives The study aim was to evaluate the utility of 2-fraction, dose-staged Gamma Knife radiosurgery (GKRS) in patients with large, high-risk brain metastases (BMs). Methods A total of 63 large BMs in eloquent areas in 61 patients were treated with GKRS in 2 reduced doses. Treatment planning was conducted on the 50% isodose line and included the whole tumor volume as seen on T1 contrast-enhanced and T2-weighted magnetic resonance imaging sections. The median margin and central dose were 12 Gy and 24 Gy, respectively, for both fractions. Patients were assessed using the Graded Prognostic Assessment, Recursive Partitioning Analysis, and Score Index for Radiosurgery. Results Thirty-two patients (53%) had been diagnosed with multiple BMs, and extracranial metastases were present in a majority of patients before GKRS treatment. Significant decreases in tumor volume were observed between the first and second treatment stages. At 3-month follow-up, a majority of patients presented with stable or decreased lesion volumes. The remaining patients showed intralesional hemorrhaging or increasing edema that was managed conservatively. Three patients were diagnosed with tumor progression at the last follow-up and received microsurgical treatment. The median time to radiologic progression was 7 months. The median survival time after initial BM diagnosis was 6 months. Survival times were significantly longer than 3 of 4 calculated prognostic survival estimates. Conclusion The new 2-fraction, dose-staged GKRS concept seems to be a well-tolerated and effective treatment option for large BMs. This method may be indicated in elderly patients or patients with surgical contraindications with large or high-risk brain metastases.

Background: We evaluated Gamma Knife radiosurgery (GKRS) as a treatment option for patients with recurrent glioblastoma. Patients and Methods: 42 patients with histopathologically diagnosed recurrent grade IV tumor were treated with GKRS. All patients had undergone standard multimodal first-line treatment. The average time from diagnosis to GKRS was 17.0 months. The median target volume was 5.1 cm3. The median margin dose was 10 Gy and the median central dose 20 Gy. In a subset of patients, O6-methylguanine methyltransferase (MGMT) promoter methylation analysis by pyrosequencing was performed. Results: Most patients did not develop complications after GKRS. Time to radiological progression after initial GKRS was 4.4 months (95% CI: 3.1-5.7 months). Radiological progression mainly occurred beyond the GKRS-irradiated area. The median survival time after initial GKRS was 9.6 months (95% CI: 7.7-11.5 months). The median overall survival time from diagnosis was 25.6 months (95% CI: 21.8-29.3 months). Patients with MGMT promoter methylation survived significantly longer (33.4 months; 95% CI: 21.2-45.5 months) compared to patients without MGMT promoter methylation (16.0 months; 95% CI: 8.0-23.9 months). Conclusion: GKRS seems to be a relatively safe salvage treatment option for recurrent glioblastoma for highly selected patients but must be seen as part of a multimodal treatment algorithm.

OBJECTIVEThe authors present long-term follow-up data on patients treated with Gamma Knife radiosurgery (GKRS) for acoustic neuroma.METHODSSix hundred eighteen patients were radiosurgically treated for acoustic neuroma between 1992 and 2016 at the Department of Neurosurgery, Medical University Vienna. Patients with neurofibromatosis and patients treated too recently to attain 1 year of follow-up were excluded from this retrospective study. Thus, data on 557 patients with spontaneous acoustic neuroma of any Koos grade are presented, as are long-term follow-up data on 426 patients with a minimum follow-up of 2 years. Patients were assessed according to the Gardner-Robertson (GR) hearing scale and the House-Brackmann facial nerve function scale, both prior to GKRS and at the times of follow-up.RESULTSFour hundred fifty-two patients (81%) were treated with radiosurgery alone and 105 patients (19%) with combined microsurgery-radiosurgery. While the combined treatment was especially favored before 2002, the percentage of cases treated with radiosurgery alone has significantly increased since then. The overall complication rate after GKRS was low and has declined significantly in the last decade. The risk of developing hydrocephalus after GKRS increased with tumor size. One case (0.2%) of malignant transformation after GKRS was diagnosed. Radiological tumor control rates of 92%, 91%, and 91% at 5, 10, and 15 years after GKRS, regardless of the Koos grade or pretreatment, were observed. The overall tumor control rate without the need for additional treatment was even higher at 98%. At the last follow-up, functional hearing was preserved in 55% of patients who had been classified with GR hearing class I or II prior to GKRS. Hearing preservation rates of 53%, 34%, and 34% at 5, 10, and 15 years after GKRS were observed. The multivariate regression model revealed that the GR hearing class prior to GKRS and the median dose to the cochlea were independent predictors of the GR class at follow-up.CONCLUSIONSIn small to medium-sized spontaneous acoustic neuromas, radiosurgery should be recognized as the primary treatment at an early stage. Although minimizing the cochlear dose seems beneficial for hearing preservation, the authors, like others before, do not recommend undertreating intracanalicular tumors in favor of low cochlear doses. For larger acoustic neuromas, radiosurgery remains a reliable management option with tumor control rates similar to those for smaller acoustic neuromas; however, careful patient selection and counseling are recommended given the higher risk of side effects. Microsurgery must be considered in acoustic neuromas with significant brainstem compression or hydrocephalus.

OBJECTIVETreatment of parasagittal meningiomas is still considered a challenge in modern microsurgery. The use of microsurgical resection, radiosurgery, or a microsurgery-radiosurgery combination treatment strategy is often debated. The aim of this study was to evaluate the treatment of parasagittal meningioma and provide evidence that a multimodal approach reduces complication rates and achieves good tumor control rates.METHODSThe authors retrospectively reviewed long-term follow-up data on 117 patients who had been treated for parasagittal meningiomas at their institution between 1993 and 2013. Treatment included microsurgery, Gamma Knife radiosurgery (GKRS), and radiotherapy.RESULTSThe median tumor volume prior to the first microsurgical resection was largest in the microsurgery-radiosurgery combination treatment group. Invasion of the superior sagittal sinus was significantly associated with a Simpson Grade IV resection and subsequent radiosurgery treatment. The Simpson resection grade did not influence time to progression or recurrence in benign meningioma cases. Complete sinus occlusion was followed by microsurgical resection of the occluded sinus, by tumor resection without resection of the sinus, or by GKRS. Histopathology revealed WHO Grade I tumors in most patients. However, a high percentage (33%) of atypical or malignant meningiomas were diagnosed after the last microsurgical resection. The time to recurrence or progression after microsurgery was significantly longer in patients with WHO Grade I meningiomas than in those with Grade II or III meningiomas. At follow-up, tumor control rates after GKRS were 91% for presumed meningioma, 85% for benign meningioma, 71% for atypical meningioma, and 38% for malignant meningioma.CONCLUSIONSA multimodal treatment approach to parasagittal meningiomas reduces the rate of complications. Thus, microsurgery, radiotherapy, and radiosurgery are complementary treatment options. Gamma Knife radiosurgery is safe and effective in patients with meningiomas invading the superior sagittal sinus. The procedure can be part of a multimodal treatment plan or administered as a single treatment in well-selected patients.

In this study we report and analyze the results of a multimodality management concept for intracranial arteriovenous malformations (AVMs), including microsurgery, embolization, and gamma knife radiosurgery. The study population consists of a consecutive series of 294 patients treated for 304 intracranial AVMs over a 10-year period.

The purpose of this study was to review our experience with a multimodality treatment approach in the management of cerebral arteriovenous malformation (AVM) in children.We retrospectively analysed a consecutive series of 56 children who harboured a cerebral AVM and were treated at our institution between 1988 and 2008. During the whole treatment period, a combined treatment strategy, including microsurgery, endovascular treatment and gamma knife radiosurgery, was used.Of the 56 patients (median age, 14.0; range, 3 months-18 years) reported, 36 (64.3%) were admitted after AVM rupture; of these, only one AVM (1.8%) was considered untreatable. In 30.9% (17/55) of the treated patients, a single treatment measure was sufficient to attain angiographic cure of the AVM. Among these, six patients (10.9%) had microsurgical AVM resection, four patients (7.3%) underwent endovascular treatment, and another seven patients (12.7%) underwent radiosurgical management of the AVM. The majority of the population (38/55; 69.1%) underwent combined treatment: 21 patients (38.2%) received embolisation followed by radiosurgery of the remnant nidus, ten patients (18.2%) underwent embolisation with subsequent surgical resection of the residual AVM, three patients (5.5%) had radiosurgery after incomplete surgical AVM nidus resection and another four patients (7.3%) required a combination of all three treatment modalities to achieve permanent angiographic cure of the AVM. We observed good clinical outcomes (Glasgow Outcome Scale 5 and 4) in 94.6% of the children. Complete angiographic obliteration was achieved in 93.3% of the patients treated.A multimodality treatment approach in children harbouring cerebral AVMs leads to excellent angiographic and clinical outcomes.

Background: The authors retrospectively compared the results of three different treatment modalities (surgery, conventional radiotherapy and gamma knife radiosurgery) in patients with paragangliomas of the temporal bone, in order to determine the optimal current treatment concept. Method: Between 1978 and August 2001, 53 patients (12 men and 41 women; mean age, 58.3 years; range, 17 to 84 years) with paragangliomas of the temporal bone were treated at the neurosurgery and ENT departments of the University of Vienna. According to the Fisch classification, 6 patients had class B tumours, 20 had class C, and 27 patients had class D tumours. Thirty-two patients (mean age, 57.0 years; 6 B, 14 C, 12 D) underwent surgery. In 17 cases the tumour was embolised prior to surgery. Nine patients (mean age, 73.9 years; 6 C, 3 D) received primary radiotherapy (median total dose, 46.8 Gy). Six patients (mean age, 73.5 years; 6 D) underwent primary radiosurgery (median centre dose 24, Gy) and 6 patients (6 D) admitted from other departments with recurrent tumours adjuvant radiosurgery (median centre dose, 25.5 Gy). Findings: In 20 of the surgical cases (62.5%) complete tumour resection was achieved and the patients required no further treatment over a mean follow-up period of 9.1 years. Of the 12 patients with incomplete tumour resection, 9 (5 C, 4 D) received postoperative adjuvant radiotherapy and three patients (3 D) adjuvant radiosurgery. In 15 (83.4%) of the 18 patients who underwent radiotherapy the tumours showed no signs of progression and the patients remained clinically unchanged over a mean period of 9.4 years. Three patients (16,6%) experienced progression of their tumour within an average period of 2.8 years. In the 15 patients who underwent primary radiosurgery, an objective 100% tumour control rate with no evidence of progression of disease was observed. Interpretation: The results indicate that the most effective current treatment option for patients with paragangliomas of the temporal bone is a single-stage radical tumour resection, performed in advanced tumours as an interdisciplinary neuro-otosurgical procedure. For subtotally resected or non-resectable tumours, gamma knife radiosurgery has proved to be a safe and effective treatment modality.

This study was performed to assess the impact of gamma knife radiosurgery (RS) in the treatment of glomus jugulare tumors. Between February 1993 and February 1999, thirteen patients (9 women, 4 men; mean age 63.5 years, range 29 to 79 years) underwent stereotactic radiosurgery for glomus jugulare tumors with the Leksell Gamma Knife at the Neurosurgical Department of the University of Vienna. Four patients, mean age 74.5 years, range 67 to 79 years, underwent radiosurgery as the only treatment. Nine patients received radiosurgery as adjuvant therapy after previous treatment had failed: surgical resection in 9 patients and additional fractionated external beam radiation in two of these patients. Pretreatment evaluation included the staging of all tumors according to the Fisch Classification: De1 (7), De2 (1), Di1 (4) and Di2 (1). The mean follow-up period was 4.2 years, range 0.7 to 6.7 years. Ten patients, 77 %, were treated prior to 1997, the mean follow-up period being 5 years. Six patients showed no clinical changes, while six experienced an improvement of their clinical symptoms and neurological deficits. One patient was lost to follow-up. Radiation-induced transient cranial nerve neuropathies were observed in two patients. Serial MRI scans revealed tumor control in all patients, with unaltered tumor size in 10 and shrinkage in three patients. The results indicate that RS is an attractive treatment option for glomus jugulare tumors and will occupy an increasingly important role in the management of these tumors in selected patients.

The authors report on their series of 40 patients with 41 acoustic neurinomas (ACNs), including one patient with bilateral acoustic neurinomas suffering from neurofibromatosis type 2 (NF II) who were treated with the gamma knife unit at their institution between August 1992 and October 1995. Of these 41 tumours, 21 ACNs had been operated on before (1 to 4 times), 20 ACNs were exclusively treated by gamma knife radiosurgery (GKRS). The maximal axial tumour diameter ranged from 6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7 mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to 17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters). Central loss of contrast enhancement was observed in 78% of the patients within six to 12 months after radiosurgery. Thirty-two patients were observed over a minimum follow up period of at least 36 months, 9 patients were lost to follow up as they died of unrelated causes or refused further check-ups. Within the follow up period of up to seven years, magnetic resonance imaging (MRI) control scans revealed the tumour diameter stable or decreased in 29 cases and increased in three tumours. Of 14 patients with useful hearing before treatment, 9 patients were examined in addition to pure tone audiogramm by measurement of brainstem auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of these patients showed a postoperative loss of the cochlea function. According to slight alterations of the cochlea function (cochlea summating action potential), pure tone audiometry of those patients revealed only slight changes of the hearing level (HL) within a maximum range of +/-15 Decibel (dB). The hearing threshold improved in two, was stable in four and deteriorated in three patients, respectively. We observed postradiosurgical aggravation of a pre-existing facial weakness in two out of 13 patients, a new occurrence of facial palsy was seen in two cases (four years after treatment), one of them was previously operated on and both suffered from cystic degeneration with mass effect. Tinnitus improved in six out of 13 patients, deteriorated in two and never appeared as a new permanent sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom, improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo increased in six out of 23, was stable in 8 and decreased in nine out of 23 patients each. GKRS proves to be a safe and highly satisfactory therapeutical option or addition to open surgery, especially for radiologically verified regrowing residual ACNs, but also as primary treatment in selected patients. A high rate of tumour control can be achieved with an acceptable rate of neurological deficits.

Stereotactic radiosurgery (RS) and surgery have proved to be effective treatment modalities for brain metastasis. We followed 133 patients whose treatment for intracranial disease was either RS or a single surgical resection at the University of Vienna from August 1992 through October 1996. All patients who received additional Whole Brain Radiotherapy were included. This was a retrospective, case-control study comparing these treatment modalities. Sixty-seven patients were treated by RS and 66 patients were treated by microsurgery. The median size of the treated lesions for RS patients was 7800 mm3, and 12500 mm3 for microsurgery patients, respectively. The median dose delivered to the tumour margin for RS patients was 17 gray. The median survival for patients after RS was 12 months, and 9 months for patients after microsurgery. This difference was not statistically significant (p = 0.19). Comparison of local tumour control, defined as absence of regrowth of a treated lesion, showed that tumours following RS had a preferred local control rate (p0.05). Univariate and multivariate analysis showed that this fact was due to a greater response rate of "radioresistant" metastasis to RS (p0.005). Postradiosurgical complications included the onset of peritumoural oedema (n = 5) and radiation necrosis (n = 1). Two patients after microsurgery experienced local wound infection. One postoperative death occurred due to pulmonary embolism in this group. On the basis of our data we conclude that RS and microsurgery combined with Whole Brain Radiotherapy are comparable modalities in treating single brain metastasis. Concerning morbidity and local tumour control, in particular in cases of "radioresistant" primary tumours, RS is superior. Therefore we advocate RS except for cases of large tumours (3 cm in maximum diameter) and for those with mass effect.

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.

Hintergrund Die stereotaktische Bestrahlung uvealer Melanome stellt einen neuen Therapieansatz dar. Vorliegende Studie untersucht die lokale Tumorkontrolle und Nebenwirkungen nach stereotaktischer Teletherapie uvealer Melanome mit einer Dosis zwischen 41 und 71 Gy.

From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from renal cell carcinoma were treated with the Leksell Gamma Knife at the University of Vienna. At the time of diagnosis 13 patients had single and 10 patients presented with multiple metastatic lesions with a total of 44 metastases in MRI scans. Median tumour volume was 5500 cmm (range 100-24000 cmm). Predominant neurological symptoms and signs were different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median dose of 22 Gy (range 8-30 Gy) at the tumour margin. Nine patients underwent a combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10-22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30 Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of 96%. Rapid neurological improvement after GKRS was seen in 17 patients. The median survival time was 11 months; the one-year actual survival in this unselected group was 48%. Five long term survivors were still alive, 18 patients had subsequently died, 15 of them of general tumour progression. GKRS induces a significant tumour remission accompanied by rapid neurological improvement and therefore provides the opportunity for extended high quality survival. Neither local tumour control was improved nor CNS relapse free survival was prolonged significantly by additional WBRT.

Department of Endocrinology, University Hospital Maastricht, The Netherlands. bwo@sint.azm.nlA 50-year-old female patient with Cushing's disease had undergone transsphenoidal removal of the pituitary adenoma and conventional radiotherapy in 1988. Since no remission was achieved, she underwent bilateral adrenalectomy in May 1989. During out-patient follow-up, she developed signs and symptoms due to invasive Adrenocorticotrophic hormone (ACTH)-producing macroadenoma (Nelson's syndrome) in 1994. ACTH levels at that time were 3400 ng/l. Near-total surgical resection of a 2.0 x 2.5 pituitary tumour which slightly extended laterally into the cavernous sinus was achieved by subfrontal approach in June 1994. However, she rapidly developed a recurrence of her complaints, with a visual field defect inferior-nasal of the left eye, and a second operation was carried out in November 1994. Culture of the tumour's cells revealed significant inhibition of ACTH production by bromocriptine. Adjuvant treatment with this drug therefore was started in November 1994. Because of the rapid recurrence it was decided to treat her with gamma-knife radiosurgery. The dose that was given in January 1995 was 12 Gy to the border and 40 Gy into the centre of the tumour. During a follow-up of more than 2 years, no recurrence, but even a minor reduction of tumour mass was observed by magnetic resonance imaging (MRI). Plasma ACTH levels decreased gradually to levels between 200 and 400 ng/l, and ophthalmologic complaints disappeared. It is concluded that gamma-knife radiosurgery may be a good alternative for patients with Nelson's syndrome who have rapidly recurring disease.

Objective To evaluate treatment options for brainstem cavernous malformations (BSCMs) using the results from a center with long-standing experience in microsurgical resection and Gamma Knife radiosurgery (GKRS) treatment of BSCMs. Methods Study participants were 67 symptomatic patients with BSCMs who were treated either microsurgically ( n = 29) or radiosurgically ( n = 38). Patients were followed for a minimum of 2 years (median, 7.7 years). A recent follow-up was performed. Results Patients receiving surgical treatment had mainly large, superficially seated lesions and experienced preoperative hemorrhages more often and presented with higher preoperative modified Rankin Scale scores. Patients receiving GKRS harbored smaller, deep-seated lesions, reflecting a selection bias. In both treatment groups, patients presented with significantly better modified Rankin Scale scores at follow-up than before intervention. Overall annual preoperative hemorrhage rates were 3.2% in microsurgery patients and 2.3% in radiosurgery patients. In the preoperative observation period, the rehemorrhage rate was 25.1% for microsurgery patients and 7.2% for radiosurgery patients. Hemorrhage rate after GKRS decreased significantly to 0.6% after 2 years. The postoperative hemorrhage rate was 8.8% but only for microsurgery patients with residual lesions. Advancements in microsurgical techniques improved surgical outcomes, resulting in a high total excision rate in the modern era. Conclusions In the treatment of BSCM, patient selection and timing of surgery are crucial. If applied in a multidisciplinary neurosurgical center, microsurgery and radiosurgery are complementary treatment options that both result in reduced bleeding rates and improvement of clinical outcome.

Von Juli 1993 bis Februar 1995 wurden 10 Patienten mit ausgedehnten Ziliarkorpermelanomen mit einer Prominenz von 9 mm oder mehr, die einer chirurgischen Exzision oder einer Brachytherapie nicht mehr zuganglich gewesen waren, mit den Leksell Gamma Knife radiochirurgisch behandelt. Die Tumorhohe vor der Behandlung betrug 10,9 ± 1,5 mm. Alle Tumore wurden am Rand mit zumindest 60 Gray, im Mittel mit 69 ± 12 Gray bestrahlt. Diese Gesamtdosis wurde stets in zwei gleich grose Fraktionen aufgeteilt und innerhalb von 4 bis 14 Tagen verabreicht.

✓ Tumor necrosis factor-α (TNFα) protein and messenger (m)RNA distribution was studied in biopsy samples of glial brain tumors, using immunohistochemistry andin situhybridization with molecular probes, to investigate the role of this cytokine in tumor proliferation and immunological host defense. Focal expression of TNFα was detected in four of four glioblastomas, one of two anaplastic astrocytomas, and four of five low-grade astrocytomas, regardless of their subtype or grade of malignancy, but in none of the normal peritumoral brain tissues used as controls. The TNFα protein and mRNA were present in reactive astrocytes and protoplasmic tumor cells, confined to areas of leukocyte or T-lymphocyte infiltration, and less pronounced in tumor cells at the edge of necrosis. Additionally, TNFα reactivity was found in infiltrating macrophages and perivascular microglia. Immunohistochemistry andin situhybridization for TNFα showed comparable reaction patterns and numbers of TNFα-positive cells, even though the sensitivity ofin situhybridization was significantly higher. Quantitative evaluation of TNFα protein, TNFα mRNA, and leukocyte infiltration revealed a significant positive correlation between the TNFα-positive reactive astrocytes and the number of lymphocytes present in corresponding areas. Together, these data lead to the conclusion that TNFα in reactive astrocytes and monocytic cells within tumor areas of high leukocyte infiltration and in tumor cells at the border of necrosis may represent one defense pathway of the immune system against tumor proliferation.

BACKGROUND Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

200 stereotactic biopsies were evaluated. The validity of the intraoperative histopathological results were compared with the final diagnosis using conventional embedding and staining techniques. Further comparison between the histology of the biopsy and the post mortem or open operative findings were possible in 41 cases. Discrepancy was found in one case regarding the tumor detection, and in three cases regarding the tumor grading. The mortality in our patients was 1% and the morbidity 3%. Stereotactical biopsy had a low risk even in deep brain regions such as basal ganglia, mesencephalon, and pons. At the same time the high histologic validity makes the CT-guided stereotactical biopsy recommendable in all lesions not operated by an open resection before any conservative or palliative therapy is started.

The value of DNA Topoisomerase IIalpha expression as a proliferation marker in meningiomas was investigated. The correlation to MIB-1 expression and tumor grade in 85 meningiomas (60 classical, 19 atypical and 6 anaplastic) was analysed by immunohistochemistry. MIB-1 labeling indices (LI) were 1.1% (+/- 0.85) for classical meningiomas, 1.9% (+/- 1.5) for atypical meningiomas and 5.6% (+/- 4.1) for anaplastic meningiomas, differences statistically significant (p = 0.03, < 0.0001, < 0.0001). Topoisomerase IIalpha LIs were 1.4% (+/- 1.2) for classical, 3.2% (+/- 2.4) for atypical and 9.7% (+/- 6.6) for anaplastic meningiomas, differences statistically significant (p = 0.003, < 0.0001, < 0.0001). Proliferation indices based on cells staining for MIB-1 and Topoisomerase IIalpha correlated highly with one another (r= 0.906, p

We present 25 pituitary adenomas that were confirmed surgically to have invaded the cavernous sinus space. The surgical results are compared with the preoperative magnetic resonance imaging findings. For comparable radiological criteria, we classified parasellar growth into five grades. This proposed classification is based on coronal sections of unenhanced and gadolinium diethylene-triamine-pentaacetic acid enhanced magnetic resonance imaging scans, with the readily detectable internal carotid artery serving as the radiological landmark. The anatomical, radiological, and surgical conditions of each grade are considered. Grades 0, 1, 2, and 3 are distinguished from each other by a medial tangent, the intercarotid line--through the cross-sectional centers--and a lateral tangent on the intra- and supracavernous internal carotid arteries. Grade 0 represents the normal condition, and Grade 4 corresponds to the total encasement of the intracavernous carotid artery. According to this classification, surgically proven invasion of the cavernous sinus space was present in all Grade 4 and Grade 3 cases and in all but one of the Grade 2 cases; no invasion was present in Grade 0 and Grade 1 cases. Therefore, the critical area where invasion of the cavernous sinus space becomes very likely and can be proven surgically is located between the intercarotid line and the lateral tangent, which is represented by our Grade 2. We also measured tumor growth rates, using the monoclonal antibody KI-67, which shows a statistically higher proliferation rate (P < 0.001) in adenomas with surgically observed invasion into the cavernous sinus space, as compared with noninvasive adenomas.

Background In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents. Methods Data from 114 consecutive patients who had access to targeted agent were analyzed for response rates (ORR), progression free survival (PFS) and overall survival (OS). All patients diagnosed with BM underwent local, BM-specific treatment before initiation of medical treatment. Results Data of 114 consecutive patients who had access to at least one type of targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC) patients (10.5%) were diagnosed with BM. Systemic treatment consisted of sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non-BM-patients, respectively (p = 0.232). The median overall survival for patients with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 - 47.0) (p = 0.358), respectively. No patient died from cerebral disease progression. ECOG Performance status and the time from primary tumor to metastases (TDM) were independent risk factors for short survival (HR 2.74, p = 0.001; HR: 0.552, p = 0.034). Conclusions Although extracerebral metastases determine the outcome of patients with BM, the benefit from targeted agents still appears to be limited when compared to patients without BM.

The expression of leucocyte adhesion molecules was studied on cerebral endothelia by immunocytochemistry. In peritumoral "normal" brain tissue we found low endothelial expression of ICAM1, LFA3, CD44, and CD9, whereas VLA1 was present on vessels in high incidence and density. LFA1, CD2, and CR3 were found on intraluminal and parenchymal leucocytes, but were absent on brain vessels. In brain tumors and inflammatory brain lesions, we observed an up-regulation of endothelial ICAM1 and LFA3 expression, whereas other adhesion molecules on endothelial cells remained unchanged. Within the brain parenchyma, ICAM1 and LFA3 were found on astrocytes and tumor cells; on the contrary, LFA1 was expressed on microglial cells similar to CR3. CD44 and CD9 showed a diffuse neuropil expression in normal and tumoral tissue, whereas VLA1 was not expressed on any parenchymal cells. Our data show that multiple different adhesion molecules are present on blood-brain barrier endothelium (BBB) under normal conditions and some adhesion molecules are up-regulated in brain tumors and under inflammatory conditions. The presence of adhesion molecules in the vessel walls as well as on parenchymal cells like astrocytes and microglia may guide inflammatory cells into and through the brain in the course of immune surveillance and inflammation.

Objective: Surgical resection of skull base meningiomas is often limited due to involvement of crucial neural structures. Within the last two decades gamma-knife radiosurgery (GKRS) gained increasing importance as adjunct treatment following incomplete resection and as an alternative treatment to open surgery. However, reports of long-term results are still sparse. We therefore performed this study to analyze the long-term results of GKRS treatment of skull base meningiomas, following our previously published early follow-up experience. Methods: A retrospective analysis was conducted of the medical files for gamma-knife and surgical treatments; clinicoradiological findings and outcomes were assessed, focusing on tumor control, clinical course, and morbidity. Results: Between 1992 and 1995, we treated 36 patients with skull base meningiomas using GKRS (male-to-female ratio, 1:5; mean age, 59 years; range, 44–89 years). Twenty-five patients were treated with GKRS following open surgery, and 11 patients received GKRS alone. Tumor control, neurological outcomes, and adverse effects were analyzed after a long-term follow-up period (mean, 103 months; range, 70–133 months) and compared with our previous results after an earlier, shorter follow-up period (mean, 48 months; range, 36–76 months). Control of tumor growth was achieved in 94% of patients. Compared with the early follow-up period, the late neuroradiological effects of GKRS on skull base meningiomas were: continuing tumor shrinkage in 11 cases (33%), stable tumor size in 20 cases (64%), and tumor progression in 2 meningiomas (6%). The neurological status revealed improvement in 16 patients (44%), stabilization in 19 patients (52%), and deterioration in 1 patient (4%). Adverse side effects of GKRS were found during the early follow-up period only. Conclusions: Our data confirm that GKRS is not only a safe and effective treatment modality for skull base meningiomas in a short-term observation period; its safety and effectiveness was also concluded in a mean long-term follow-up period of more than 8 years, and tumor shrinkage and clinical improvement was found to continue during the long-term follow-up period.

Proliferative activities were determined in 72 human brain tumors, including 20 metastatic carcinomas, 41 gliomas, 8 meningiomas and 3 hematological tumors. Immunocytochemical techniques included labeling with monoclonal antibody (mAb) to bromodeoxyuridine (BrdU) which identifies S phase cells after previous in vitro BrdU incubation and paraffin embedding of fixed tissue specimens, and with mAb Ki-67 which reacts, in frozen sections, with a nuclear antigen expressed by all proliferating cells. BrdU labeling index (LI), Ki-67 LI and mitotic index (MI) correlated well with histological malignancy. Among the three proliferation indices, Ki-67 LI and BrdU LI were highly significantly correlated. With the exception of hematological malignancies, hyperbaric oxygenation of in vitro BrdU labeling did not significantly increase BrdU LI or depth of BrdU penetration into tissue. This study indicates that in vitro BrdU labeling is a useful alternative to Ki-67 immunolabeling of human brain tumor specimens. By such determination of tumor proliferation, it might be possible to design a more adequate postoperative therapy tailored to patients individually.

Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.

OBJECTIVE: Surgical resection of cranial base meningiomas is often limited owing to involvement of crucial neural structures. Within the last 2 decades Gamma Knife radiosurgery (GKRS) has gained increasing importance as an adjunct treatment after incomplete resection and as an alternative treatment to open surgery. However, reports of long-term results are still sparse. We therefore performed this study to analyze the long-term results of GKRS treatment of cranial base meningiomas, following our previously published early follow-up experience. METHODS: A retrospective analysis of the medical files for Gamma Knife and surgical treatments, clinicoradiological findings, and outcome was carried out focusing on tumor control, clinical course, and morbidity. RESULTS: Between 1992 and 1995, we treated 36 patients with cranial base meningiomas using GKRS (male:female ratio, 1:5; mean age, 59 yr; range, 44–89 yr). Twenty-five patients were treated with GKRS after open surgery, and 11 patients received GKRS alone. Tumor control, neurological outcomes, and adverse effects were analyzed after a long-term follow-up period (mean, 103 mo; range, 70–133 mo) and compared with our previous results after an early follow-up period (mean, 48 mo; range, 36–76 mo). Control of tumor growth was achieved in 94% of patients. Compared with the early follow-up period, the late neuroradiological effects of GKRS on cranial base meningiomas were continuing tumor shrinkage in 11 patients (33%), stable tumor size in 20 patients (64%) and tumor progression in two meningiomas (6%). The neurological status improved in 16 patients (44%), remained stable in 19 patients (52%), and deteriorated in one patient (4%). Adverse side effects of GKRS were found only during the early follow-up period. CONCLUSION: Our data confirm that GKRS is not only a safe and effective treatment modality for cranial base meningiomas in short-term observation, but also in a mean long-term follow-up period of more than 8 years. Tumor shrinkage and clinical improvement also continued during the longer follow-up period.

Background Brain metastases have evolved from a rare to a frequently encountered event in advanced breast cancer due to advances in palliative systemic treatment. Patients and methods All Patients treated at our centre from 1994 to 2004 with WBRT for brain metastases from breast cancer were included. We performed a multivariate analysis (Cox regression) to explore which factors are able to influence significantly cerebral time to progression (TTP) and overall survival (metastatic sites [visceral versus non-visceral], Karnofsky performance score [KPS], age, intensified local treatment [boost irradiation, neuro-surgical resection] further systemic treatment). Results Overall 174 patients, median age 51 years, range 27–76 years, were included. Median TTP was 3 months (m), range 1–33+ m. Median overall survival was 7m, range 1–44m. Factors significantly influencing TTP were KPS ( p =0.002), intensified local treatment ( p p =0.001). Factors significantly influencing survival were intensified local treatment ( p =0.004), metastatic sites ( p =0.008), KPS ( p =0.006), and palliative systemic treatment ( p Conclusion As shown by the significant influence of metastatic sites, some patients die from their advanced systemic tumour situation before they would die from cerebral progression. In other individuals however, intensified local treatment and systemic treatment appear to influence cerebral time to progression and overall survival.

Ki-67 antigen is used as a marker of proliferative activity that is linked to growth rate, invasiveness and prognosis of pituitary adenomas. So far the distribution of Ki-67 index within an individual adenoma has not been investigated. If Ki-67 antigen expression differs significantly within an individual pituitary adenoma, a sampling error may result when assessing small fragments of adenoma tissue. Such a potential error would diminish the value of Ki-67 as a tool for postoperative patient management considerations. The aim of the present study was to assess Ki-67 proliferation rates in different regions of pituitary adenomas and to statistically analyse these data for potential regional differences within each tumor. Ki-67 proliferation index was assessed in smear preparations of 100 specimens of 26 consecutive patients operated on for pituitary adenoma in the Department of Neurosurgery, Medical University Vienna. Depending on the size and extent of the tumor, a mean of 4 tissue samples (range 2-8) was selected intraoperatively from each adenoma from endosellar, suprasellar, parasellar, and basal sellar dural locations. Overall mean cell proliferation rate measured by Ki-67 was 1.81 +/- 0.90% (range 0.33-3.43%). Histologically invasive adenomas had significantly higher mean Ki-67 proliferation index in all samples from the same tumor than non-invasive adenomas (2.01 +/- 0.91% vs. 1.11 +/- 0.59%; P = 0.024). Multiregional sampling revealed a homogenous distribution of Ki-67 index throughout an individual adenoma with no significant differences between any two different regions on t-test. Our data confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki-67 index of a single biopsy is representative for the whole individual adenoma. Thus Ki-67 index can be considered a reliable parameter for assessment of cell proliferation rate in adenoma biopsies and may be used for postoperative patient management considerations.

To investigate the diagnostic accuracy and current role of intraoperative cytologic smears of central nervous system tumors.Retrospective analysis of 4,172 patients operated on during 1985-1999, with 3,541 intraoperative smears performed during open procedures and 631 during stereotactic biopsies.Complete correlation with the final diagnosis was achieved in a mean of 89.8% (range, 83-93.7% per year). Diagnostic accuracy increased to 95% on average (range, 91.5-96.7% per year) when cases of partial correlation, mainly due to grading deviations, were included. The most accurate intraoperative diagnoses were obtained in cases of meningioma (97.9%), metastasis (96.3%) and glioblastoma (95.7%). A significant reduction in diagnostic accuracy was observed in cases of oligodendroglioma (80.9%) and ependymoma (77.7%). Besides diagnosis and grading, smear cytology provided resection guidance in cases of well-delineated tumors.Intraoperative smears in neurosurgery are easy to obtain and inexpensive and have high diagnostic accuracy. In addition to stereotactic biopsy procedures, intraoperative smears permit reliable intraoperative guidance during lesion targeting and resection.

Purpose: The development of brain metastases represents an ominous event for patients with colorectal cancer. We evaluated results following stereotactic radiosurgery (SR) for patients with metastatic colorectal cancer to identify efficacy of SR and prognostic factors for survival. Methods: This is a retrospective study of 60 brain metastases from colorectal cancer in 35 consecutive patients who underwent SR from January 1993 to December 1996. Thirteen patients also underwent additional whole-brain radiation therapy (WBRT). The median dose delivered to the tumor margin was 20 Gray (range 16–28 Gy), in most cases the tumor enclosing the 50% isodose (range 40–60%). Patients were classified into two groups: SR with and SR without WBRT. Univariate and multivariate testing was performed to determine significant prognostic factors. Results: The median survival time was 6 months after SR and 40 months after diagnosis of primary tumor. A Karnofsky performance scale >70 was a significantly favorable prognostic factor in uni- and multivariate testing. Post-SR imaging was evaluated in 32 patients and in 54 cerebral lesions. Local tumor control was revealed in 94% of patients and 96% of treated tumors. Two patients developed local recurrences, and remote brain disease was revealed in five. No patient experienced a new focal neurologic deficit due to SR. The addition of WBRT to SR did not improve survival and local tumor control rates. Distant control rate was borderline in univariate analysis and significantly improved for patients who received additional WBRT in multivariate analysis. Conclusion: SR for brain metastases from colorectal cancer results in a high local tumor control rate of 94% associated with few complications and therefore provides patients with a higher quality of their remaining life.

We want to describe the rare case when an intramural macrocyst within an acoustic neurinoma (ACN) treated by gamma knife radiosurgery (GKRS) ruptured, followed by an impressive decrease of tumor volume and improvement of neurological symptoms. In a 59-year-old female patient, a large ACN with a hugh intramural macrocyst was diagnosed. As she refused open surgery, we performed GKRS covering the tumor margin and the cyst with 11 Gy. Seven months after treatment symptoms worsened slightly. Magnetic resonance imaging (MRI) revealed no significant change of tumor volume. One year after GKRS she felt a sensation behind her treated ear, followed by an immediate improvement of all her symptoms. Trigeminal hypaesthesia and vertigo disappeared, tinnitus ameliorated. A control MRI showed the cystic compartment no longer, the solid part shrunk within the following six years. Within the whole follow-up period hearing was stable. To our knowledge this is the first report of a macrocyst within an ACN to rupture after GKRS.

Background. The standart surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas. Method. Between September 1992 and October 1995, SRS using the Leksell Gamma Knife was performed on 46 patients (f:m=35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n=46) were devided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes. Findings. The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33%, stable clinical course in 58% and a persistant deterioration of clinical symtoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced. Interpretation. GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margine dose.

Background and purpose: To evaluate prospectively local tumor control and morbidity after 1‐3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. Material and methods: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8^2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm 3 were treated with one fraction of 45 Gy. The mean total dose was 54 ^ 8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. Results: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. Conclusions: Stereotactic external photon beam irradiation and a total dose of 45‐70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eyepreserving treatment in uveal melanoma. q 2000 Elsevier Science Ireland Ltd. All rights reserved.

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3–). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto- oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas.

To study local tumor control and radiogenic side-effects after fractionated stereotactic radiotherapy for uveal melanoma.Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with stereotactic 6 MeV LINAC (Saturne 43, General Electric, France) in conjunction with a stereotactic frame system (BrainLAB, Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0 +/- 2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment.After a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed.Optical fixation of the eye allows high precision stereotactic radiotherapy with small safety margins. Fractionated stereotactic radiotherapy and 70 Gy total dose delivered in 5 fractions seems to be appropriate for local tumor control in uveal melanoma. Further long-term studies with extended number of patients will be necessary to conclude on the use of linac-based fractionated stereotactic radiotherapy for uveal melanoma.

The aim of this study was to determine the shuttle dose for all collimator helmets (4, 8, 14 and 18 mm) of the Gamma Knife, model B, in Vienna, Austria. The additional dose accumulated during the transport of the patient in and out of the treatment position should be considered in the dose planning procedure of multicentre treatment regimens and in fractionated stereotactic Gamma Knife radiotherapy. The GafChromic film study was basically used to determine the shuttle dose of all four collimator helmets. In addition, measurements with an ionization chamber (18 and 14 mm collimator) - and, for the 18 mm collimator helmet, TLD dosimetry - were performed in order to confirm the GafChromic film data. The shuttle dose ranged between 99.6 and 183.5 mGy, depending mainly on the size of the collimator and the irradiated isocentres at the half-life activity of Co-60 in a brand new Gamma unit. Our film-generated data were in good correlation with the dose levels obtained with the ionization chamber and the TLD dosimetry, showing a dose difference of less than 0.8%. Since it was possible to verify the shuttle dose even for the 4 and 8 mm collimator helmets, we consider it a non-negligible factor and would advocate the inclusion of the shuttle dose in radiosurgical dose planning.

We developed a new TLD array for precise dose measurement and verification of the spatial dose distribution in small radiation targets. It consists of a hemicylindrical, tissue-equivalent rod made of polystyrene with 17 parallel moulds for an exact positioning of each TLD. The spatial resolution of the TLD array was evaluated using the Leskell spherical phantom. Dose planning was performed with KULA 4.4 under stereotactic conditions on axial CT images. In the Leksell gamma unit the TLD array was irradiated with a maximal dose of 10 Gy with an unplugged 14 mm collimator. The doses delivered to the TLDs were rechecked by diode detector and film dosimetry and compared to the computer-generated dose profile. We found excellent agreement of our measured values, even at the critical penumbra decline. For the 14 mm and 18 mm collimator and for the 11 mm collimator combination we compared the measured and calculated data at full width at half maximum. This TLD array may be useful for phantom or tissue model studies on the spatial dose distribution in confined radiation targets as used in stereotactic radiotherapy.

A series of 45 patients who have undergone combined treatment for cerebral arteriovenous malformations (AVM's) is presented. All patients underwent additional radiosurgery after endovascular and/or surgical treatment. Stereotactic radiosurgical treatment using the Gamma knife has been available in our institution since 1992. The treatment strategy for brain AVM's has changed since that time. The possibility for total cure of partially embolised AVM's, where other treatment options had been exhausted, increased with adjunctive radiosurgery. Complex or giant AVM's in eloquent areas can now be treated using radiosurgery after embolisation and/or microsurgery, with minor risk of neurological deficit. In all 45 patients treated since September 1992 at the University of Vienna, embolisation was performed to reduce the size of the nidus in order to facilitate surgical resection or radiosurgical treatment. In 37 patients radiosurgery was performed after endovascular treatment only, and in 8 patients radiosurgery was performed after embolisation and surgery. All AVM's were classified according to Spetzler's Grading System. 31 patients (68.9%) were classified as Grade 3 or 4. Two patients (4.5%) were classified as Grade 5. In a mean follow up time of 16 months (range 2–40), there were 15 complete obliterations and 2 patients with unexpected residual AVM after two years. Of patients who required staged radiosurgical therapy, 12 have been followed for less than two years after their final procedure. In an additional 12 patients the follow-up period is less than 12 months. 4 patients were lost to follow up. There is a morbidity of 8.8% and no mortality in this patient group.

This report is a list of simple but effective techniques for marking important structures intra-operatively. During the last 2 years in 52 patients intra-operative marking techniques have been used. In 37 cases a small piece of fat has been taken. In 10 patients it was done by a radiopaque Barium impregnated silicon sphere and in 5 patients with a piece of a monofilament suture. Postoperative checks were done by conventional X-ray, computer tomography and Magnetic Resonance Imaging. The indication in all cases was to offer landmarks helpful for planning postoperative radiosurgery. In case of fat and radiopaque Barium impregnated silicone spheres the markings were always well defined and clear in contrast. In those cases where a piece of monofilament suture was used it was impossible to get clear postoperative information. In general there were no intra- or postoperative complications. All markers were well tolerated and no side effects have been observed so far. The advantages and disadvantages of each of these possibilities are described and discussed.

We designed a suction fixation system for the radiosurgical treatment of intraocular malignancies with the Leksell Gamma Knife. Our device consists of a circular suction chamber and an adjustable unit which is fixed to the Leksell stereotactic head frame. All components are made of plastic in order to avoid artifacts in CT or MRI. A permanent suction of 600-800 mbar is provided by a standard vacuum pump, powered by a portable battery. In the Gamma Knife Unit of the Neurosurgical Department at the University of Vienna, we successfully used this device. Up to April 1994 we successfully performed 25 radiosurgical treatments in 12 patients with large or extra-large uveal melanomas and in 1 patient suffering from a choroidal metastasis.

Radiosurgery of AVM’s is gaining in popularity and is advocated by many for the treatment of lesions less than 3 cm in diameter. During a 17 month period 33 patients with cerebral AVM’s were treated with radiosurgery. All regions of the brain were represented in the series including brain stem. A mean follow-up of 10.8 months revealed a 6% rebleed rate and a 9% total complication rate. Multimodality therapy including embolization and surgery is recommended for the treatment of AVM’s and radiosurgery is seen as an important adjunctive treatment option.

Both, neuroendoscopy and radiosurgery, are upcoming techniques in neurosurgery and become nowadays more and more important. In planning radiosurgical interventions it is very important to have both, the information about the morphology of the pathology itself, and also a clear understanding from the surrounding structures. Neuroendoscopic techniques gives the possibility to demonstrate well known structures without prior dissection. This paper focuses on these anatomical informations which might be relevant in planning further radiosurgical interventions especially in cases of the vascularization of the cranial nerves and the arachnoid membranes, these structures appears much more complex than described in “common” neuroanatomical textbooks. Endoscopie techniques also better demonstrate the real in vivo relationships and gives so a better understanding for interpreting “planning” MRI and CT scans. We therefore consider that neuroanatomical studies under a neuroendoscopical view are very important and could be very helpful in planning radiosurgical intervensitons.

We designed a suction fixation system for the radiosurgical treatment of intraocular malignancies with the Leksell gamma unit (gamma knife). Our device consists of a circular suction chamber and an adjustable unit to be fixed to the Leksell stereotactic head frame. All components are made of plastic materials in order to avoid artifacts in CT or MRT imaging. A permanent suction of 600 to 800 millibars is provided by a standard vacuum pump, powered by a portable battery. Suction times up to 40 minutes were well tolerated in all cases.