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.

Summary. 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.

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.

Summary 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.

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.

OBJECTIVES A series of three recurrent central neurocytomas treated by gamma knife radiosurgery (GKRS), which were initially totally resected, are described. Up to now, no reports exist on this treatment modality for this rare tumour entity. METHODS Three male patients, aged between 20 and 25 years, presented with large intraventricular tumours. Total tumour removal was achieved by a single surgical procedure (one patient) or two operations (two patients). Neuropathological investigation showed a central neurocytoma, immunohistochemically all three tumours expressed a neuronal antigenetic profile typical for neurocytomas, and the MIB-1 proliferation index ranged from 2.4% to 8.7%. Each patient experienced a tumour recurrence after 5 to 6 years. The recurrence was multifocal in two and a singular tumour mass in one patient. Gamma knife radiosurgery was performed. The tumours were enclosed within the 30% to 60% isodoseline, and delivered a tumour marginal dose of 9.6 to 16 Gy. During the follow up period, the patients were tested clinically and the volume of the tumours was measured on MRI. RESULTS Within follow up periods of 1 to 5 years, control MRI showed a significant decrease of the tumour mass in all cases. None of the patients developed new neurological symptoms after GKRS. Two patients returned to work in their previous employment, whereas one patient remained permanently disabled due to a pre-existing visual impairment and abducens palsy. CONCLUSION GKRS proved to be a useful tool in the treatment of recurrent central neurocytomas. Tumour control and even tumour shrinkage can be achieved with a single procedure and a low risk of morbidity.

DAVF's at the SSS are extremely rare and usually present with intracranial haemorrhage (ICH) or a progressive neurological deficit. Due to their midline location and multiple arterial supply, endovascular treatment alone often fails in eliminating the fistula. Therefore, endovascular, combined with neurosurgical and/or radiosurgical treatment is often needed to cure the patient. We summarized our experience with three male patients over a ten-year period who suffered from dAVF's involving the middle and posterior third of the SSS. Two of them presented with an ICH during the clinical course. Despite multiple transarterial embolisations, complete fistula occlusion could not be achieved in any of them. Nevertheless, neurological symptoms improved in all cases. One patient refused further treatment and died six years later due to an ICH. Another patient was finally cured by microsurgical coagulation of the fistula. In the remaining patient stereotactic radiosurgery (SRS) was performed after nearly complete endovascular occlusion. We strongly recommend microsurgery and/or radiosurgery as adjunctive measures, if embolisation alone fails to eliminate these dangerous fistulae.

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.

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 GL 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 eye preserving treatment in uveal melanoma. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

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 (p < 0.05). Univariate and multivariate analysis showed that this fact was due to a greater response rate of "radioresistant" metastasis to RS (p < 0.005). 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.

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.

In in vitro and in vivo studies, episclerally sutured radio-opaque markers were evaluated as localizers for better determination of the clinical tumour volume prior to stereotactic radio-therapy of uveal melanoma. Four different types of markers were studied in vitro: tantalum marker, 2.5 mm in diameter; ring-shaped markers custom-designed in polymethyl methacrylate (PMMA), 2.6 mm and 3.0 mm in diameter; and barium-impregnated silicone rubber spheres, 2 mm in diameter. In vivo PMMA markers 3.0 mm in diameter and barium-impregnated silicone rubber spheres 2 mm in diameter were used. The best results were obtained with the barium-impregnated silicone rubber spheres both in vitro and in vivo. For the CT-delineation of selected uveal melanomas with either a flat discoid shape or flat tumour extensions or when adjacent serous retinal detachment is present, small episclerally sutured barium-impregnated silicone rubber spheres are useful as localizers for determining the clinical tumour volume.

Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with a stereotactic 6 MV linac in conjunction with a stereotactic frame. Immobilization of the eye was ensured with an optical fixation system. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. A total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. After a follow-up of at least 6 months, further tumor growth was stopped in all 8 eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7, 13 and 31%, respectively. Only mild subacute side-effects have been noticed. Conclusions: Optical fixation of the eye allows high precision stereotactic radiotherapy with small security margins. Fractionated stereotactic radiotherapy and 70 Gy total dose delivered in 5 fractions seems to be effectively for local tumor control in uveal melanoma.

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.