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Biomedical subjects

J Voges

Publications and source records attributed to J Voges.

At least 19 recordsLinked to original sources

Interstitial irradiation with stereotactically implanted I-125 seeds for the treatment of cerebral glioma.

Owing to its low rate of side effects and its high efficacy, interstitial irradiation with low-activity seeds should be the first therapeutic step in small (maximal diameter 40 mm), well-circumscribed, low-grade gliomas affecting the brain stem, other midline structures, or eloquent cerebral areas. In anaplastic gliomas, a therapeutic schedule using low-activity seeds and combining interstitial irradiation with radiotherapy (reduced boost dose of 15-30 Gy) seems to be more effective than interstitial irradiation alone. Compared with interstitial irradiation with high-activity seeds, this combined irradiation schedule caused no space-occupying radiation necrosis. Thus, it can be recommended as up-front treatment in patients with small (maximal diameter <40 mm) inoperable anaplastic gliomas. The use of high-activity I-125 seeds and interstitial irradiation at comparably high dose rates, integrating a small penumbra of normal brain tissue into the treatment volume, improved survival significantly in patients with primary highly malignant gliomas. In patients with recurrent tumors, the same treatment schedule did not substantially prolong survival compared with results obtained after resection plus radiotherapy. Owing to the high frequency of space-occupying radiation necrosis (40-60%), this schedule is only applicable in surgically accessible tumors. The application of low-activity I-125 seeds (in primary glioblastomas in combination with radiotherapy, in recurrent tumors without radiotherapy) yielded a median survival comparable with conventionally treated patients. There was no need for reoperation because of radiation necrosis. Thus, this treatment schedule is useful in both operable and surgically inaccessible glioblastomas.

Journal Article

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Adult

Linear accelerator radiosurgery for recurrent malignant tumors of the skull base.

The efficacy of linear accelerator-based radiosurgery for patients who have preirradiated recurrent nasopharyngeal carcinomas and unresectable recurrent sarcomas invading the base of skull was assessed. Thirteen patients were treated: 8 patients had carcinomas arising from the nasopharynx (lymphoepithelioma, 4; squamous cell carcinoma, 2; adenoid-cystic, 2); 5 patients had sarcomas (rhabdomyosarcoma, 1; chordoma, 1; chondrosarcoma, 1; hemangiopericytoma, 2). All patients had had repeated tumor resections or irradiation, hindering any further conventional fractionated radiotherapy or surgery. Convergent-beam irradiation was performed with a modified linear accelerator (8-MeV photons). Because of irregular tumor configuration, multiple (up to seven) isocenters had to be used in 10 of 13 patients to match the target volume with the reference isodose (60%-80%). Each isocenter was irradiated with 6 to 10 arcs. The median planning target volume was 33 mL (4-128 mL) and the median dose was 15 Gy (9-24 Gy). Median survival time was 9 months in 8 patients who had recurrent nasopharyngeal carcinomas. Three patients who had complete or partial tumor remission survived 1.5 to 3.5 years. All of the sarcoma patients responded to radiosurgery. After a follow-up of 28 to 67 months, 4 of 5 patients are alive. This investigation demonstrates that radiosurgery is an effective tool in palliative treatment for patients who have recurrent, extensively pretreated nasopharyngeal cancer. Patients who have recurrent sarcomas of the base of skull may be treated for long-term palliation or even for cure.

Adult

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult

Risk analysis of LINAC radiosurgery in patients with arteriovenous malformation (AVM).

The purposes of this analysis were the evaluation of the toxicity of stereotactic single dose irradiation in patients with an arteriovenous malformation (AVM) and the comparison of the authors' own results with already existing risk prediction models. Computed-tomography (CT) or magnetic-resonance (MR) images, and clinical data of patients treated with linear accelerator radiosurgery for an AVM were analysed retrospectively. Using the Cox proportional hazards model (1), the relevance of treatment parameters and dose-volume relationships to the occurrence of radiation-induced tissue changes (oedema and localised blood-brain-barrier breakdown) were assessed. The 81 patients selected for analysis had a mean follow-up of 28.9 months (range: 9.0-65.7 months). Radiation-induced tissue changes (22 out of 81 i.e. 27.2%) were documented on CT or MR images 6.3-33.8 months after radiosurgery (median time: 12.8 months). The actuarial risk at 2 years was 32.1% for the development of neuroradiological changes and 20.1% for the development of symptomatic tissue alteration. The coefficient of total volume receiving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model. These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Actuarial Analysis

Cystic craniopharyngioma: long-term results after intracavitary irradiation with stereotactically applied colloidal beta-emitting radioactive sources.

OBJECTIVE: Long-term follow-up data were analyzed to assess the value of intracavitary irradiation with stereotactically applied beta-emitting radioisotopes for the treatment of craniopharyngioma cysts. METHODS: Sixty-two of 70 consecutive patients with predominantly cystic craniopharyngiomas were selected for retrospective analysis. Beta-Emitting isotopes were injected intracystically using a computed tomography-guided and computer-assisted three-dimensional stereotactic treatment planning and application system (cumulative dose to the inner surface of the cyst wall, 200 Gy). RESULTS: The tumor response rate gained with yttrium-90-labeled silicate (66 of 78 cysts) or phosphorous-32-labeled chromic phosphate (8 of 78 cysts) was 79.5%. Four cysts treated with rhenium-186-labeled sulfate did not respond. Mean survival after intracavitary irradiation was 9.0 +/- 0.9 years (median follow-up, 11.9 yr). In patients with solitary cysts, the mean survival was 12.5 +/- 1.4 years (actuarial 5- and 10-yr survival rates, 80 and 64%, respectively). Six months postoperatively, visual deficits (38 of 62 patients) had improved in 23 patients and were stable in 15 patients. The side effects that occurred 6 to 12 months after treatment with yttrium-90 were complete blindness (three patients), worsening of visual field cuts (one patient), third nerve palsy (one patient), and diabetes insipidus and/or panhypopituitarism (three patients). CONCLUSIONS: Intracavitary irradiation using yttrium-90 or phosphorous-32 is highly effective in the treatment of cystic craniopharyngiomas. If applied as initial treatment in patients with solitary cysts, it is the only required therapy over a long period.

Adolescent

11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds.

Forty-six patients with suspected brain tumors were investigated by positron emission tomography (PET). Using 11C-methionine PET, the spatial extent of increased uptake in gliomas was larger than that of contrast enhancement on CT/MR images in 67% or the same in 33%. Ten of 46 patients treated with brachytherapy for low-grade gliomas were also investigated with 18F-2-fluorodeoxyglucose (FDG)-PET. One year after seed implantation, the glucose metabolism had not changed, but the decline of methionine uptake was significant. In conclusion, 11C-methionine PET may improve tumor delineation and, following brachytherapy, provides more information on the therapeutic effects than FDG.

Adult

Risk analysis of linear accelerator radiosurgery.

PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Adolescent

LINAC-radiosurgery (LINAC-RS) in pituitary adenomas: preliminary results.

From 8/90 through 4/94, 32 consecutive patients with recurrent pituitary macroadenoma (PA) were treated with LINAC-RS after tumour resection and/or radiotherapy. Single doses ranging from 8-20 Gy (median: 14.5 Gy) were applied in 14 patients with acromegaly, 5 with Cushing's disease, 4 with Nelson tumours, 5 with prolactinomas and in 4 with nonfunctioning PA's. Retrospective analysis of 26 patients with a follow-up of > or = 6 months revealed no significant endocrinologic response in patients with Cushing's disease, Nelson tumour or prolactinoma. In contrast in 12 evaluated patients with acromegaly within 6-36 months after LINAC-RS the median GH-value decreased significantly. In 3 nonfunctioning PA's a tumour volume reduction has been observed. We conclude, that LINAC-RS with moderate single doses might be a safe and beneficial treatment in patients with acromegaly or nonfunctioning PA's resistant to conventional therapy. In Cushing's disease, Nelson tumours or prolactinomas higher doses seem to be required.

Adenoma

Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy.

We investigated whether 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) and carbon-11 methionine are suitable tracers to monitor the effects of therapy for low-grade gliomas. Ten patients with low-grade glioma without previous treatment were studied with FDG positron emission tomography. Additionally, l-[methyl-11C]methionine uptake was measured in five subjects before and 1 year after computerized tomography (CT)-guided stereotactic and computer-assisted implantation of iodine-125 seeds. All scans were 3D-matched to CT, isodose volumes were determined, and changes in glucose metabolism and methionine uptake were evaluated in tumour and brain tissue as a function of radiation dose. After 1 year glucose metabolism was not significantly altered up to a radiation dose of 300 Gy, whereas methionine uptake showed a significant dose-dependent decrease. Higher rates of decline were found in tumours with high basal methionine incorporation activity before therapy. These data suggest that measurement of methionine uptake is more suitable than measurement of FDG uptake for monitoring therapeutic effects in low-grade gliomas.

Adult

Serum albumin (SA) accumulation by bronchogenic tumours: a tracer technique may help with patient selection for SA-delivered chemotherapy.

Systemic toxicity and inadequate tumour uptake of chemotherapeutic agents limit effective therapy of disseminated malignant disease. We seek to use macromolecules for improved delivery of therapeutic agents to tumours, and hope to use radiotracer procedures to identify those malignancies able to accumulate the transport molecule. A literature search identified in vitro and animal experimental data which indicated that serum albumin is taken up in malignancies. Selected cytostatic drugs can be bound to albumin, which suggests the suitability of the molecule as a potential transport vehicle. We therefore evaluated indium-111 labelled human serum albumin (HSA) to determine the frequency of its accumulation in bronchogenic tumours. Single-photon emission tomographic (SPET) images were obtained in 23 patients 48 h after intravenous injection of 1.5 mCi 111In diethylenetriamine penta-acetic acid (DTPA)-HSA. SPET imaging with technetium-99m labelled erythrocytes was included in the protocol to assess the influence which vascularity has on the HSA-based images. All patients went on to surgery. We documented the histological diagnosis, T-stage and differentiation grade. The scintigraphic examination demonstrated HSA uptake in three squamous cell carcinomas and four adenocarcinomas. Of these, six malignancies accumulating HSA had 2.2-5.4 times, the tracer concentrations observed in comparable background regions. Small cell carcinoma failed to accumulate the labelled HSA during the 2-day scintigraphic evaluation. The HSA images did not appear to represent tumour vascularity. T-stage and differentiation grade failed to predict which tumours would demonstrate HSA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents

Linac radiosurgery in brain metastases.

Brain metastases are usually well-circumscribed and more or less spherical lesions. These conditions meet the criteria for radiosurgery (RS). A pilot study initiated by our group in 1983, demonstrated the effectiveness of Linac-RS in the treatment of solitary brain metastases with low radiosensitivity. A second trial including patients with 1-3 metastases started in 1990. By April 1993, 46 patients had been treated in this series. The radiation doses delivered to the tumour margin ranged from 10 to 25 Gy, and were chosen with respect to size, number and location of the tumours or previous whole brain radiotherapy (WBRT), decreasing mainly with increasing tumour volumes. 34/46 patients had a follow-up of more than 12 weeks. In 7/46 patients the disease progressed rapidly during the first weeks after RS and follow-up examinations were not performed. 5/46 patients had a follow-up of less than 6 weeks and follow-up CT/MR-examinations were not available. 14/46 patients received WBRT before RS. The regularly performed follow-up examinations (clinical status, CT-/MR-examinations in 6 or 12 weekly intervals) revealed tumour progression in 5/34 patients. Permanent cessation of the growth (11/34), tumour shrinkage (18/34) and decrease of surrounding oedema together with clinical amelioration have been observed a few weeks after radiosurgery. The median follow-up was 50 weeks. 14/46 patients died due to generalized progression of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Linac-accelerator-radiosurgery.

A survey is given of the actual possibilities and limitations of the use of linear accelerators (Linac radiosurgery systems) for intra = cranial radiosurgery. Depending on the collimator size, spherical fields from 5-54 mm in diameter can be irradiated with dose gradients from 10% (large fields) to 20% (small fields) per millimeter distance between surface and treatment volume. This is comparable to the possibilities of Gamma-Knife and Proton-irradiation. Optimal mechanical adjustment of gantry and linac table are necessary for the required stability of the isocenter. Mechanical inaccuracy should be smaller than 0.8 mm. Advanced computerized 3D-treatment planning systems are indispensable prerequisites for accurate treatment and use of the flexibility of the linac system. Future developments are outlined.

Brain

Interstitial irradiation of cerebral gliomas with stereotactically implanted iodine-125 seeds.

Ninety-seven consecutive patients with primarily inoperable or only partially resectable gliomas have been analysed retrospectively. Mean tumour surface doses of 70 Gy (low grade gliomas) and 56 Gy (high grade gliomas) have been applied with stereotactically implanted Iodine-125 seeds at low dose rates. Patients with a glioma grade III or grade IV and permanent seed implantation additionally received a fractionated external beam irradiation. With mean follow-up times of 55.8 months (glioma grade I), 51 months (glioma grade II) and 59.6 months (glioma grade III) the estimated mean survival probabilities are 105 months, 102 months and 65.7 months respectively. In the glioma grade IV group the estimated mean survival time has been 15.6 months after continuous interstitial irradiation (response rate: 36%). Temporary interstitial irradiation in cases with a glioma grade IV (dose rate: 2.1 Gy/day) caused initial tumour shrinkage in 77%. Neurological deficits following radiation induced vasogenic oedema were reversible in 2 patients and irreversible in another 2 patients. 6 years after the Iodine-125 implantation and continuous interstitial irradiation 1 patient developed a severe localised radiation necrosis.

Adolescent

CT-guided and computer assisted stereotactic biopsy. Technique, results, indications.

On the base of a stereotactic device originally described by Riechert and Mundinger a three-dimensional localization and treatment planning system for CT-guided computer assisted stereotactic procedures has been developed. The experience with 338 patients, in which image guided stereotaxy has been used for the assessment of various intracerebral lesions, is presented. In 54 of these patients the cannula was introduced with a 20 MHz Doppler-probe positioned at the tip of the needle. A comparison of tissue specimens taken stereotactically with tissue material after tumour resection and/or autopsy was performed in 35 patients. The accuracy of the histological diagnosis was 88%. Bleeding as a complication due to the stereotactic intervention occurred in 8 patients (2.4%). Two of these patients had a fatal outcome (mortality: 0.6%). The morbidity (transient and permanent deterioration of the clinical status) was 1.2%.

Adolescent

Interstitial irradiation of a large, low grade ependymoma with stereotactically implanted iodine-125 seeds. Case report.

In this case report a patient with a large intraventricular benign ependymoma is presented. The tumour was treated with stereotactically implanted Iodine-125 seeds and interstitial irradiation. Extension (diameter: 6.5 cm) and volume (112.5 ml) of the lesion caused the application of an unusually low dose (tumour surface dose: 40 Gy). The tumour shrank significantly within a few weeks. Follow-up at nearly 5 years shows the patient to be tumour free.

Adult

Correlation of glucose consumption and tumor cell density in astrocytomas. A stereotactic PET study.

To determine histological correlates of the variability of glucose consumption in astrocytomas, the authors performed positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and matched the PET scans three-dimensionally with computerized tomography scans obtained in a stereotactic frame before biopsy. Ten patients with astrocytomas of World Health Organization Grade 2 or 3 were studied; patients with glioblastomas, oligodendrogliomas, or oligoastrocytomas were excluded from the study to avoid any confounding effects of different cell types and necroses. In samples of pure tumor, glucose consumption correlated significantly with cell density, but not with nuclear polymorphism. It is concluded that tumor cell density is a major determinant of glucose consumption in astrocytomas. The use of PET with FDG may help to locate the highest cell density and thus improve the diagnostic yield of stereotactic biopsy.

Adult