Biomedical subjects

J Debus

Publications and source records attributed to J Debus.

At least 109 records · Page 6Linked to original sources

PubMed2000

[High-dose, stereotactic, one-time radiotherapy with curative intent for peripheral lung cancer].

In peripheral non small cell lung cancer without metastasis, surgical resection achieves 5-year survival rates of at least 65%. In functionally inoperable patients radiation therapy offers the second best changes. However, in cases of severe emphysema with severely limited lung function even conventional radiation therapy is prohibited because of possible fibrotic reactions of the lung parenchyma. For such patients high dose rate stereotactic one-time radiation therapy may be an option. According to the study protocol of the DKFZ Heidelberg a dose rate of 24 Gy at the iso-center is applied with the linear accelerator in a single session. The recognisable tumour is irradiated with 22 Gy (90% isodose included). 20 Gy are applied to the tumour plus 6 millimeters safety margin. Prerequisites of such a therapy are a detailed computer-based planning using CT scans and an exact positioning with immobilisation of the patient. The irradiation is ideally performed under general anesthesia with high-frequency jetventilation to avoid movements due to breathing. We report on this new therapeutic modality in a patient with lung emphysema having a T2 tumour.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Selection of beam angles for radiotherapy of skull base tumours using charged particles.

The geometrical treatment configuration for skull base tumours is investigated using three different sources of information. First, an analysis of treatment angle combinations for 50 patients treated with conventional conformal radiation therapy is performed. In a second step, nine treatment plans for a hypothetical heavy ion gantry were prepared. Finally, cylindrical projections of the organs at risk are introduced as a tool to analyse the distribution of treatment angles as well as the treatment geometry for each patient. The results of the analysis for conventional therapy clearly show treatment angle combinations that are preferably used. These findings are also supported by the geometrical analysis using the cylindrical projections. The majority of treatment angles for heavy ions also seem to be confined to those regions. In one case, however, the sharp distal dose fall-off of the heavy ions allowed a beam direction outside these conventionally used regions. The advantages of a heavy ion gantry versus a fixed horizontal beam line are shown by comparison of treatment plans for both systems. Treatment angle combinations are suggested that should be accessible for any beam line design using either fixed beams or a gantry.

Biophysical Phenomena↗

PubMed2000

Arteriovenous malformations: assessment of gliotic and ischemic changes with fluid-attenuated inversion-recovery MRI.

RATIONALE AND OBJECTIVES: To evaluate the diagnostic potential of fluid-attenuated inversion-recovery (FLAIR) MRI in the assessment of patients with cerebral arteriovenous malformations (AVMs) and to correlate the MR findings with clinical symptoms, in particular, perilesional gliosis and ischemic changes. METHODS: Forty-five patients with cerebral AVMs were examined with FLAIR and conventional T1- and T2-weighted MRI by using identical slice parameters. Images were assessed in a two-reader study for detection and delineation of gliotic and ischemic tissue. Also, the extent of the flow void phenomenon and image artifacts were evaluated. RESULTS: FLAIR MRI was rated superior to the conventional T2-weighted fast spin-echo imaging in the assessment of intralesional and perilesional gliosis. The superior delineation was a result of the suppression of cerebrospinal fluid, mild T1 weighting, and the more pronounced flow void phenomenon. There was no significant correlation between the extent of gliosis and the clinical symptoms. However, larger AVMs had more extensive signal changes. CONCLUSIONS: FLAIR is a valuable MRI technique to assess gliotic and ischemic changes in or close to cerebral AVMs. Because gliotic and ischemic changes are common findings and are known to be associated with epilepsy, in the assessment of these patients FLAIR is clinically useful and may guide decisions about treatment-for instance, the extent of surgical resection of the potential epileptogenic focus.

Adult↗

PubMed1999

Noninvasive patient fixation for extracranial stereotactic radiotherapy.

PURPOSE: To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. METHODS AND MATERIALS: Thirty-one CT studies (> or = 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. RESULTS: The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm+/-1.2 mm (laterolateral [LL]), 1.4 mm+/-1.0 mm (anterior-posterior [AP]), 2.3 mm+/-1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm+/-1.0 mm (LL), 1.2 mm+/-0.7 mm (AP), 1.8 mm+/-1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine (in the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be < or = 3.6 mm. CONCLUSION: The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae.

Casts, Surgical↗

PubMed1999

Synergistic interaction of ultrasonic shock waves and hyperthermia in the Dunning prostate tumor R3327-AT1.

Pulsed high-energy ultrasound shock waves (PHEUS), similar to those used for clinical lithotripsy, can deposit energy deep in tissue and thereby destroy the microvasculature of solid tumors. We investigated the potential of PHEUS, generated by an electromagnetic shockwave source (19 kV capacitor voltage, 1 Hz pulse frequency), as a local cancer-therapy modality alone and in combination with local tumor hyperthermia (43.5 +/- 0.1 degrees C, 30 min). Copenhagen rats transplanted with the anaplastic Dunning-prostate-tumor sub-line R3327-AT1 received 1000 PHEUS pulses, which delayed tumor growth by one tumor-doubling time (5 days). Histopathology revealed hemorrhage, disruption of tumor vasculature, and necrosis in the focus of the sound field. Bromodeoxyuridine (BUdR) incorporation was significantly lower in PHEUS-treated tumors than in controls. Dynamic magnetic resonance imaging (MRI) studies using gadolinium-DTPA as contrast agent showed a strong reduction of tumor perfusion after PHEUS treatment, although this effect was partly reversible within 3 days after PHEUS. While hyperthermia alone produced no significant delay in tumor growth, the combination of PHEUS and hyperthermia produced tumor-growth delay by 2 tumor-volume-doubling times. The maximum growth delay was achieved when PHEUS and hyperthermia were separated by 24 hr at the time of maximum perfusion reduction indicated by MRI. Thus, the cytotoxic effect of PHEUS was enhanced by hyperthermia in the anaplastic prostate tumor R3327-AT1 grown on Copenhagen rats in a synergistic manner, due to blood-flow reduction. In conjunction with other agents, such as hyperthermia, PHEUS might become a local cancer-therapy modality in solid tumors accessible to ultrasound.

Animals↗

PubMed1999

Fractionated stereotactic radiotherapy (FSRT) for optic glioma.

PURPOSE: To determine efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with optic glioma. METHODS AND MATERIALS: Ten patients suffering from optic glioma were treated by FSRT between December 1990 and December 1995 at the German Cancer Research Center (DKFZ) in Heidelberg. Eight patients were treated for progressive recurrent tumor following partial tumor resection and 2 patients were treated postoperatively. Dose distributions were calculated by a 3D treatment planning system (Voxelplan, Heidelberg). Patients were treated with a noninvasive repeatable stereotactic fixation system using a manually driven midsize multileaf collimator attached to a linear accelerator. We applied a median prescribed total dose to the isocenter of 52.4 Gy with a median daily fraction size of 1.8 Gy. RESULTS: All patients treated by definitive radiotherapy remained free from local tumor progression during the follow-up period (range 12-72 months) except the 1 patient treated for recurrence after previous radiotherapy. A complete remission was achieved in 3 patients with subsequent improvement of visual acuity. None of the patients with locally controlled tumor experienced any further impairment of vision. One patient developed new ACTH deficiency. No other clinically significant late effects attributable to radiotherapy were observed. CONCLUSION: FSRT permits treatment of optic glioma with excellent tumor control and without clinically relevant morbidity. Compared to conventional techniques there is the potential of sparing the pituitary gland in chiasmatic lesions.

Adolescent↗

PubMed1999

Quantification of microglial late reaction to stereotactic irradiation of the rat brain using computer-aided image analysis.

The role of microglial cells in the late delayed reaction following radiotherapy of brain tumors has not been elucidated. To investigate the late delayed response of microglial cells to radiation, we stereotactically irradiated spherical treatment volumes in the right frontal lobe of rat brains. Doses of 20, 30, 40, and 50 Gy were used in combination with two different collimators. The response of microglial cells at 10 and 19 months after irradiation was determined with Anti-CD 11 b/c (Ox 42) as an immunohistochemical marker. For evaluation of immunostaining, we developed a method using computer-aided image analysis in which the ratio of the area of stained cells to that of nonstained brain tissue is calculated. In addition, quantification of Ox-42+ cells per microscopic field was performed. Animals treated with 30 Gy or more had significantly increased total areas of staining at both time points studied. In contrast, the number of stained cells at 10 months increased significantly only in animals treated with 30 or 40 Gy. Likewise, at 19 months, this number increased significantly only in animals treated with 40 Gy or more. These results indicate that computer-aided determination of the area of stained cells is more sensitive than the counting of stained cells. We have demonstrated that microglial cells respond to stereotactic irradiation in a dose-dependent fashion. The image analysis we employed for this purpose is a systematic method to evaluate immunohistochemical staining.

Animals↗

PubMed1999

[Stereotactic one-time irradiation (radiosurgery). The methods, indications and results].

BACKGROUND: Stereotaxy is a method to determine a point in the patient's body by an external coordinate system which is attached to the patient. Radiosurgery uses this method for precise delivery of a high single radiation dose to the patient. The aim is to destroy the tissue in the target and to spare surrounding unaffected normal tissue by a steep dose gradient. METHODS: Three techniques of percutaneous radiosurgery are available: radiosurgery with ion beams with a cyclotron, spherical arrangement of cobalt-60 sources, the so-called gamma knife, and an adapted linear accelerator. The availability and the good clinical experience lead to a wide spread use of linear accelerator for radiosurgery in recent years. A subsequent development is fractionated stereotactic radiotherapy which combines the precision of radiosurgery with the radiobiological advantage of fractionation. RESULTS: Only a few indications for radiosurgery are proven by statistically valid studies. One of these is the treatment of small arteriovenous malformation, where obliteration rates of 80% to 100% are reported with only minor toxicity. However, the obliteration rate is reduced significantly in large arteriovenous malformations. A local control rate of 90% is obtained after radiosurgery of brain metastases which is comparable to the results of microsurgical resection followed by adjuvant whole brain radiotherapy. An ongoing EORTC study evaluates the role of adjuvant whole brain radiotherapy after radiosurgery. The survival of the patients with brain metastases is limited by the existence of progressive extracerebral disease. The role of radiosurgery in the treatment of benign tumors is currently evaluated in clinical studies which include: vestibular schwannomas, meningiomas, chordomas and chondrosarcomas and pituitary adenomas. Most of the published studies include only small tumors because radiosurgery is limited by the risk of radionecrosis of adjacent normal tissue, which shows a steep dose volume response relationship. Recent developments of stereotactic radiotherapy include the use of mini-multileaf-collimators and clinical studies on stereotactic radiotherapy of extracranial targets. CONCLUSIONS: Stereotactic irradiation is a well established treatment technique for intracranial tumors and arteriovenous malformations. Methods are available that allow optimization of dose distributions to irregularly shaped tumors for single dose as well as fractionated stereotactic irradiations by linear accelerator. Therefore the therapeutic potential of this technique has increased and enables also the extracerebral application in controlled clinical studies.

Brain Neoplasms↗

PubMed1999

Treatment planning for light ions: how to take into account relative biological effectiveness (RBE).

A new treatment planning program was developed for the heavy ion therapy facility at GSI, which is tailored to the special needs for an active beam delivery using a magnetic raster scanner. It also includes a biological model for the estimation of biological effective dose for carbon ions and realizes a fully biological treatment planning. Biological effective dose distributions and RBE maps can be displayed and assessed from the graphical user interface.

Chondrosarcoma↗

PubMed1999

The GSI Cancer Therapy Project.

At the Heavy Ion Research Institute GSI in Darmstadt an experimental cancer treatment program with a five years duration has been developed. A new method for cancer treatment with ions is applied, using rasterscan method in addition to an active pulse to pulse variation of ion beam properties, including the energy, intensity and focusing. An overview of this Cancer Therapy Project is presented, that covers both accelerator aspects to provide the required beam variations within a short time and the installations at the treatment place for rasterscan control. In addition to a description of the technical design (control-hard- and software) experimental results will be shown, containing the achieved beam properties and measurements of rasterscan performance.

Academies and Institutes↗

PubMed1999

The application of PET to quality assurance of heavy-ion tumor therapy.

At the new heavy ion tumor therapy facility of the Gesellschaft für Schwerionenforschung at Darmstadt positron emission tomography (PET) has been implemented for in-beam and in-situ therapy control, i.e. during the tumor irradiation. The components necessary for this dedicated PET-imaging and their integration into the framework of therapy planning and quality assurance of heavy ion cancer treatments are presented. Results of the first application of this PET-method to patient treatments are reported.

Germany↗

PubMed1999

The role of high-LET radiotherapy compared to conformal photon radiotherapy in adenoid cystic carcinoma.

Tumors of the base of skull represent a challenging radiooncological target due to their close proximity to dose limiting critical normal tissue structures. A critical review of the literature provides evidence that high-LET radiotherapy offers a therapeutic gain factor compared to low-LET radiation and should be the treatment of choice in advanced salivary gland malignancies, which are inoperable or not completely resected, and in recurrent disease. Modern techniques of conformal high LET radiotherapy, e.g. heavy ion beam radiotherapy, will help to reduce the long and the short term toxicity of radiotherapy.

Carcinoma, Adenoid Cystic↗

PubMed1999

[Fluid-attenuated-inversion-recovery (FLAIR) imaging in the diagnosis of cerebral gliomas and metastases].

This study demonstrates the value of a fast fluid-attenuated inversion-recovery (FLAIR) technique in the assessment of cerebral gliomas and metastases. Thirty-five patients with cerebral gliomas and 12 patients with a total of 39 cerebral metastases were examined by T2/proton density-weighted fast spin echo, fast FLAIR with and without contrast medium and contrast-enhanced T1-weighted spin echo using identical slice parameters. The images were evaluated using quantitative and qualitative criteria. Quantitative criteria were tumor-to-background and tumor-to-cerebrospinal fluid contrast and contrast-to-noise. The qualitative evaluation was performed as a multireader analysis concerning lesion detection, lesion delineation and image artifacts. In the qualitative evaluation, all readers found fast FLAIR to be superior to fast spin echo in the exact delineation of cerebral tumors (P < 0.001) and the delineation of enhancing and non-enhancing tumor parts. Fast FLAIR was superior in the delineation of cortically located and small lesions but was limited in lesions adjacent to the ventricles. Fast FLAIR provided significantly better tumor-to-CSF contrast and tumor-to-CSF contrast-to-noise (P < 0.001). The tumor-to-background contrast and tumor-to-background contrast-to-noise of the fast FLAIR images were lower than that of T2-weighted spin-echo images but were significantly increased after the application of contrast medium. FLAIR images had a more image artifacts, but these influenced the image interpretation in only two patients. Signal hyperintensities at the ventricular border were present in 92% of the patients. These are common findings in fast FLAIR and should be included in image interpretation.

Brain Neoplasms↗

PubMed1999

[Experimental external irradiation of corneal neovascularization].

UNLABELLED: The clinical effect of ionidizing radiation on ocular neovascularizations is controversial not only because of the variety of treatment modalities. The aim of our study was to investigate an experimental model which allows to evaluate radiation parameters and to study the mechanism of the inhibitory effect on neoangiogenesis. METHODS: Corneal angiogenesis was induced by use of a micropocket assay in NZW rabbits. Pellets with 500 ng bFGF in 2% methylecellulose were implanted into the stroma 2.0 mm from the limbus. Initiation of vessel growth occurred on day 3. At this time radiation was performed with different doses (single dose of 15 to 30 Gy or fractionated 5 x 5 Gy) using a 6 MeV linear accelerator. Vascular growth was quantified. RESULTS: Irradiation with a total dose of 25 Gy applied in a fractionated regimen or as single-dose irradiation on the day of surgery or on day 6 after surgery did not significantly reduce neovascular growth. In contrast, postoperative radiation therapy on day 3 was able to reduce the area of ingrowing vessels significantly (P < 0.01). In spite of the relatively high dose there were no significant side effects during the observation period of 8 weeks. CONCLUSION: Our results show that single-dose radiation (> or = 25 Gy) is sufficient to inhibit the growth of corneal neovascularizations. With this model it might be possible to investigate parameters for therapy of ocular neovascularizations as well as the underlying mechanisms.

Animals↗

PubMed1999

A treatment planning inter-comparison of proton and intensity modulated photon radiotherapy.

PURPOSE: A comparative treatment planning study has been undertaken between standard photon delivery techniques,b intensity modulated photon methods and spot scanned protons in order to investigate the merits and limitations of each of these treatment approaches. METHODS: Plans for each modality were performed using CT scans and planning information for nine patients with varying indications and lesion sites and the results have been analysed using a variety of dose and volume based parameters. RESULTS: Over all cases, it is predicted that the use of protons could lead to a reduction of the total integral dose by a factor three compared to standard photon techniques and a factor two compared to IM photon plans. In addition, in all but one Organ at Risk (OAR) for one case, protons are predicted to reduce both mean OAR dose and the irradiated volume at the 50% mean target dose level compared to both photon methods. However, when considering the volume of an OAR irradiated to 70% or more of the target dose, little difference could be shown between proton and intensity modulated photon plans. On comparing the magnitude of dose hot spots in OARs resulting from the proton and IM photon plans, more variation was observed, and the ranking of the plans was then found to be case and OAR dependent. CONCLUSIONS: The use of protons has been found to reduce the medium to low dose load (below about 70% of the target dose) to OARs and all non-target tissues compared to both standard and inversely planned photons, but that the use of intensity modulated photons can result in similar levels of high dose conformation to that afforded by protons. However, the introduction of inverse planning methods for protons is necessary before general conclusions on the relative efficacy of photons and protons can be drawn.

Algorithms↗

PubMed1999

Sonochemically induced radicals generated by pulsed high-energy ultrasound in vitro and in vivo.

The aim of this study was to evaluate the role of radicals as a mechanism of tissue damage induced by pulsed high-energy ultrasound. Transient cavitation has proved to be an important mechanism for the generation of reactive radical species during pulsed high-energy ultrasound applications. The amount of radicals studied in in vitro experiments using a chemical dosimeter based on iodine release is proportional to the number of pulses. Sonications of the R3327-AT1 subline of the Dunning prostate rat tumor transplanted in the thigh of Copenhagen rats were performed applying 500 and 2000 pulses at a pulse repetition frequency of 1 Hz. Tumor growth after treatment was compared with sham-treated controls. We were able to assess a significant growth delay, but could not find a significant difference between the two groups treated. In conclusion, radical formation does not seem to be the major mechanism for tissue necrosis induced by pulsed high-energy ultrasound.

Adenocarcinoma↗

PubMed1999

A comparison of shock wave and sinusoidal-focused ultrasound-induced localized transfection of HeLa cells.

Both shock waves and sinusoidal continuous wave ultrasound can mediate DNA transfer into cells. The relative transfection efficiencies of different ultrasound modalities are unclear. The purpose of this paper is to compare the transfection efficiency of lithotripter shock waves and focused sinusoidal ultrasound in vitro. HeLa cells were transfected with beta-galactosidase and luciferase plasmid DNA reporter. Shock waves were generated by an electromagnetic sound source. Sixty to 360 pulses at 1 Hz pulse frequency were administered at 13, 16 or 19 kV capacitor voltage. Sinusoidal focused ultrasound was generated by a single focus piezoceramic air-backed disk transducer at a carrier frequency of 1.18 MHz operated in a pulsed mode. Compared to cells mixed with DNA only, shock waves induced up to eightfold more transfected cells at a cell viability of 5%, while sinusoidal-focused ultrasound induced up to 80-fold more transfected cells at a cell viability of 45%. The corresponding transfection efficiencies of the HeLa cells were 0.08% for shock waves and 3% for focused ultrasound. These results may contribute to the selection of the ultrasound modality as a localized, noninvasive and safe tool to mediate gene transfer.

HeLa Cells↗

PubMed1999

Simultaneous assessment of cerebral hemodynamics and contrast agent uptake in lesions with disrupted blood-brain-barrier.

The purpose of this study was to develop a method that eliminates the influence of the T1 relaxation time upon the signal-time course in perfusion-weighted imaging of cerebral lesions with blood-brain-barrier (BBB) disruption. On a 1.5 T whole body clinical magnetic resonance (MR) imager, we implemented a dual-echo RF-spoiled FLASH sequence (TE=6/23.6 ms). We developed a postprocessing routine that allowed to calculate a signal-time course representing only the change in T2* and another one representing only the change in T1. Using this method, we examined 7 patients with various brain lesions showing evidence of BBB disruption. In the signal-time-curves obtained from the early echo we found a distinct signal drop due to the T2* effect. These effects could be eliminated by the correction algorithm yielding a 67% higher signal increase. Correction of the signal-time curve of the late echo yielded a more pronounced maximum signal drop and a decrease in postcontrast signal intensity. We found that without this correction the relative regional cerebral blood volume and the first moment of the concentration-time curve were underestimated by 72% and 22%, respectively. The dual echo-sequence combined with the postprocessing algorithm separates T1 and T2* effects and thus allows to assess cerebral hemodynamics and contrast agent kinetics simultaneously. This method may be a useful tool for characterizing, staging, and therapy monitoring of brain tumors.

Adult↗