Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and safety after a follow-up of over 12 years.

PURPOSE: The efficacy and safety of stereotactic radiosurgery (SRS) for treatment of intracranial meningiomas has been demonstrated in numerous studies with short- and intermediate-term follow-up. In this retrospective single-center study, we present long-term outcomes of SRS performed with a linear accelerator (LINAC) for typical intracranial meningiomas. PATIENTS AND METHODS: Between August 1990 and December 2007, 148 patients with 168 typical intracranial meningiomas were treated with stereotactic LINAC-SRS, either as primary treatment or after microsurgical resection. A median tumor surface dose of 12 Gy (range 7-20 Gy) and a median maximum dose of 24.1 Gy (range 11.3-58.6 Gy) was applied. The median target volume was 4.7 ml (range 0.2-32.8 ml, SD ± 4.8 ml). RESULTS: Overall mean radiological follow-up was 12.6 years. Tumor shrinkage was seen in 75 (44.6 %) and stable disease in 85 (50.6 %) cases. Eight of 168 meningiomas (4.8 %) showed local tumor progression. The tumor control rate (TCR) after 5, 10, and 15 years was 93.6 % at each time point, and the progression-free survival (PSF) rates were 92, 89, and 89 %, respectively. The neurological symptoms existing prior to LINAC-SRS improved in 77 patients (59.7 %), remained unchanged in 42 (32.6 %), and deteriorated in 10 (7.8 %) patients. CONCLUSION: Our study emphasizes the efficacy of LINAC-SRS for de novo, residual and recurrent typical intracranial meningiomas. A high long-term local TCR with a low morbidity rate could be achieved. LINAC-SRS should thus be considered as a primary treatment option, as one arm of a combined treatment approach for incompletely resected meningiomas, or as a salvage therapy for recurrences.

Uptake and tracer kinetics of O-(2-(18)F-fluoroethyl)-L-tyrosine in meningiomas: preliminary results.

PURPOSE: O-(2-[(18)F]Fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established PET tracer for the imaging of cerebral gliomas, but little is known about (18)F-FET uptake in meningiomas. The aim of this study was to explore (18)F-FET kinetics and tumour-to-background contrast in meningiomas of various histologies. METHODS: A group of 24 patients with suspected cerebral meningioma on MRI/CT had an additional dynamic (18)F-FET PET scan prior to surgery. Time-activity curves (TAC) of (18)F-FET uptake in the tumours and tumour-to-brain ratios (TBR) for early (3 - 14 min after injection) and late (18)F-FET uptake (20 - 40 min after injection) were analysed and compared with histological subtypes and WHO grade. (18)F-FET uptake in critical structures in the skull base was also evaluated in terms of tumour-to-tissue (T/Tis) ratio. RESULTS: TBR of (18)F-FET uptake in meningiomas was significantly higher in the early phase than in the late phase (3.5 ± 0.8 vs. 2.2 ± 0.3; P < 0.001). The difference in TBR between low-grade meningiomas (WHO grade I, 18 patients) and high-grade meningiomas (WHO grade II or III, 6 patients) was significant in the late phase of (18)F-FET uptake (2.1 ± 0.2 vs. 2.5 ± 0.2, P = 0.003) while there was no significant difference in the early phase. ROC analysis showed that TBR of (18)F-FET uptake in the late phase had significant power to differentiate low-grade from high-grade meningiomas (AUC 0.87 ± 0.18, sensitivity 83 %, specificity 83 %, optimal cut-off 2.3; P < 0.01). Evaluation of TAC yielded three different curve patterns of (18)F-FET PET uptake. Combination of TBR (cut-off value 2.3) and TAC pattern slightly improved the differentiation of high-grade from low-grade meningiomas (accuracy 92 %; P = 0.001). Analysis of background radioactivity in the skull base indicated that (18)F-FET uptake may be helpful in distinguishing meningioma tissue in the late phase. T/Tis ratios were >1.2 in all patients for the periorbita, sphenoidal sinus, pituitary gland, tentorium, bone and brain, in more than 90 % of patients for the mucosa and dura, but in only 63 % of patients for the cavernous sinus. CONCLUSION: (18)F-FET PET may provide additional information for noninvasive grading of meningiomas and possibly for the discrimination of tumour in critical areas of the skull base. A further evaluation of (18)F-FET PET in meningiomas appears to be justified.

Aminolevulinic acid-mediated photodynamic therapy of human meningioma: an in vitro study on primary cell lines.

OBJECTIVE: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. METHODS: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm²). The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. RESULTS: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001). Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 µg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. CONCLUSION: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the potential therapeutic effects of 5-ALA-PDT in vivo.

Hemodynamic stroke: A rare pitfall in cranio cervical junction surgery.

Surgical C1C2-stabilization may be complicated by arterial-arterial embolism or arterial injury. Another potential complication is hemodynamic stroke. The latter might be induced in patients with poor posterior fossa collateralization (risk factor 1) when the vertebral artery (VA) is compressed during reduction (risk factor 2). We report a clinical case where this rare situation occurred: A 72-year old patient was undergoing C1C2-stabilization for subluxation due to rheumatoid arthritis. Preoperative computed tomography angiography (CTA) had shown poor collaterals in the posterior fossa. Furthermore, intraoperative Doppler ultrasound (US) detected unilateral VA occlusion during reduction. It appeared to be a high-risk situation for hemodynamic stroke. Surgical inspection of the VA found osteofibrous compressing elements. Arterial decompression was performed resulting in the normal flow as detected by US. Subsequently, C1C2-stabilization could be realized. The clinical and radiological outcome was very favorable. In C1C2-stabilization precise analysis of preoperative CTA and intraoperative US are important to detect risk factors of hemodynamic stroke. Using these data may prevent this rare, but potentially life-threatening complication.

Enhancing the effect of 5-aminolevulinic acid based photodynamic therapy in human meningioma cells.

BACKGROUND: The interest in photodynamic therapy (PDT) in cancer treatment has continuously increased since its' advent in the 1960s. In neurosurgery, 5-aminolevulinic acid based photodynamic therapy (5-ALA PDT) is used for malignant glioma in vitro and in vivo. Data about PDT in meningioma, which is the second most frequent primary brain tumor, is sparse. Preliminary work indicated that meningiomas are more resistant to PDT than gliomas. In the present study we evaluated whether the effect of 5-ALA PDT on malignant meningioma cells can be increased by ciprofloxacin and changes in incubation time, factors known to influence the effectiveness of PDT in other tumor entities. METHODS: An in vitro-PDT model of a malignant human meningioma cell line (KT21-MG) was chosen as screening method. Cultured cells were incubated with varying 5-ALA concentrations for 4h and exposed to PDT (control group). Two experimental groups, one with 5-ALA and ciprofloxacin (group I) and one with 24-h ALA incubation time (group II), were studied, respectively. Cell viability was assessed by WST-1 assay. RESULTS: Ciprofloxacin and longer ALA incubation time significantly increased the lethal effect of 5-ALA PDT on meningioma cells. CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time. As ciprofloxacin is a common antibiotic with good tissue penetration, low toxicity and a favorable risk profile it represents a clinically interesting method for future PDT trials in meningiomas.