PubMed HealthSearch

Biomedical subjects

H Treuer

Publications and source records attributed to H Treuer.

At least 19 recordsLinked to original sources

Ionizing radiation-induced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus.

The occurrence of radiation-induced apoptosis in normal brain was investigated using an animal model of radiosurgery. Adult male Fischer rats aged 3 to 4 months were subjected to single dose convergent beam irradiation (10 Gy). Apoptotic cell death was determined by in situ labeling of DNA nick ends (TUNEL) and light microscopic evaluation of cell morphology. Five hours after irradiation, a highly significant increase of apoptotic cells in the subgranular zone of the dentate gyrus was paralleled by a corresponding significant decrease of cells immunoreactive for the proliferation marker Ki-67. Morphology, location and distribution of cells affected by radiation-induced apoptosis in the dentate gyrus subgranular zone, together with NeuN-immunohistochemistry, support the contention that these cells belong to the immature progenitor population responsible for neurogenesis in the adult rat hippocampus.

Animals

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation.

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Arteriovenous Malformations

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

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

Quantification of tumor reoxygenation during accelerated radiation therapy.

PURPOSE: To determine the effect of accelerated fractionated radiation therapy on the reoxygenation of chronic hypoxic tumor cells by means of a three-dimensional Monte Carlo simulation. MATERIALS AND METHODS: Tumor growth (cell cycle time [Tc] of 2 or 5 days), irradiation (alpha = 0.3 Gy-1, alpha/beta = 10 Gy), oxygen tension (oxygen enhancement ratio of 3.0), capillary network distortion, and shrinkage of a small (10(4)-cell) tumor were modeled on a workstation. Conventional (2 Gy delivered five times per week), accelerated (1.6 Gy delivered twice a day for 5 d/wk), and split-course (1.6 Gy delivered twice a day for 5 d/wk with a break in week 3) radiation therapies were simulated with total doses of 50-70 Gy. RESULTS: Tumors grew in cords with a central necrotic area surrounded by hypoxic cells (hypoxic fraction, 25%). If undisturbed tumor shrinkage occurred, complete reoxygenation took 2 1/2 weeks for accelerated, 3-5 weeks for split-course, or 4-6 weeks for conventional radiation therapy. If shrinkage was prevented, the hypoxic fraction rose to 90%-100% at 2-3 weeks. In the shrinking, reoxygenation tumors with a Tc of 2 days, accelerated radiation therapy increased tumor control by 40%-80% over the control with conventional radiation therapy. With split-course therapy, this advantage was lost at doses below 70 Gy. Shrinking tumors with a Tc of 5 days were all controlled with 50 Gy. CONCLUSION: Fast-growing tumors that reoxygenate by shrinking are especially sensitive to acceleration and treatment breaks.

Cell Division

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

Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation.

PURPOSE: A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. MATERIAL AND METHODS: The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm3 which were displaced by the growing tumor was simulated. Tumors contained 10(4) cells when irradiation started, intrinsic radiosensitivity was set to either low (alpha = 0.3 Gy-1, beta = 0.03 Gy-2) or high (alpha = 0.4 Gy-1, beta = 0.04 Gy-2) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time Tpot = 1.2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. RESULTS: During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (Tpot = 2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (Tpot = 1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. CONCLUSION: The simulation results suggests that shrinking of a homogeneous tumor during irradiation with restoration of the normal vascular architecture can contribute significantly to reoxygenation, which in turn has a major effect on tumor control.

Capillaries

[Dosage inhomogeneities in the matching of opposing photon fields and electron fields in head-neck tumors ].

PURPOSE: Head and neck tumors are often treated by a multiple-field technique, using a combination of opposing photon fields and electron beams in order to stay within the limit of the myelon tolerance dose. Dose inhomogeneities at field margins must be minimalized to avoid an increased rate of local recurrences or late complications. METHODS: A polystyrene phantom with a base of 12 x 16 cm was used to investigate the optimal conditions of field matching, using 9 MV photon beams and 8 to 10 MeV electron beams. The evaluation was performed by using an automatic video-densitometer and digital image processing. Dose distributions are presented as 3-dimensional plots and as dose profiles in a depth of 1.2 and 2.5 cm. RESULTS: In the neck region photon and electron fields cannot exceed a field width of 6 to 7 cm. With unmodified electron fields and opposing photon fields with a 5 mm penumbra optimal geometrical matching is achieved by using an overlap of 2 mm referring to the field margins. Related to a reference dose of 100% the dose in 1.2 and 2.5 cm depth varied between 90% and 115%. Geometrical variations at the field margins, using a gap of 3 mm or an overlap of 5 mm, result in a local underdosage of 75 to 80%, respectively an overdosage of 135 to 150% referring to the reference dose. This dose inhomogeneity occurs at a width of 1 cm around the field margins. CONCLUSIONS: Regarding clinical and physical aspects the matching of unmodified beams seems to have an advantage compared to the matching of fields with broadened penumbras. For the treatment of patients an immobilisation technique and a precise daily set up is required.

Electrons

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

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

Optimization and evaluation of landmark-based image correlation.

Image correlation methods enable the complementary use of information from different medical images of a patient. These images can be obtained from different imaging devices (CT, MR, PET), or, from one imaging device taken at different times. Unfortunately, there are few cases in which the requirements for later image correlation are taken into account at the time of image acquisition. There is therefore a need for correlation techniques requiring no preparation in advance. We have developed two correlation methods, both based on three or more anatomical or artificial landmarks, to be defined in corresponding image data sets. These methods have been evaluated with phantom data as well as with patient data. We have improved these correlation methods by using more landmarks and special selection criteria. They are applicable to all medical tomograms and to x-ray pictures taken under stereotactical conditions. The results obtained have error ranges in the order of the three-dimensional image resolution.

Diagnostic Imaging