Biomedical subjects

Thomas G Wendt

Publications and source records attributed to Thomas G Wendt.

10 recordsLinked to original sources

PubMed2006

3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing.

BACKGROUND: To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT) performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures. MATERIALS AND METHODS: 39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomitant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22). Later the dose distribution was calculated with KonRad and fluence was modified by MCP 96 alloy compensators (n = 17). Gross tumor/tumor bed (PTV 1) was irradiated up to 60-70 Gy, [5 fractions/week, single fraction dose: 2.0-2.2 (simultaneously integrated boost)], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2) with 48-54 Gy [single dose: 1.5-1.8]). Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ). RESULTS: Mean of the median doses at the parotid glands to be spared was 25.9 (16.3-46.8) Gy, for tin granulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (degree 0-2/3): xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed (degree 0-2/3): 88%/12%. 6 months postRT chronic xerostomia degree 0-2/3 was observed in 85%/15% of patients, none with degree 4 xerostomia. CONCLUSION: 3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced head and neck cancers. Since the concept of lower single (and total) doses in the adjuvantly treated volumes reduces acute morbidity 3D-c-IMRT nicely meets demands of concurrent chemotherapy protocols.

Adult↗

PubMed2005

Dosimetric quality assurance for intensity-modulated radiotherapy feasibility study for a filmless approach.

PURPOSE: Test and comparison of various 2-D real-time detectors for dosimetric quality assurance (QA) of intensity-modulated radiotherapy (IMRT) with the vision to replace radiographic films for 2-D dosimetry. MATERIAL AND METHODS: All IMRT treatment plans were created with the Konrad software (Siemens OCS). The final dose calculation was also carried out in Konrad. A Mevatron Primus (Siemens OCS) linear accelerator which provides 6-MV and 15-MV highenergy photon beams was used for the delivery of segmented multileaf-modulated IMRT. Three different 2-D detectors, each based on a different physical (interaction) principle, were tested for the field-related IMRT verification: (1) the MapCheck diode system (Sun Nuclear), (2) the I'mRT QA scintillation detector (Scanditronix/Wellhöfer), and the Seven29 ionization chamber array (PTW). The performance of these detector arrays was evaluated against IMRT dose distributions created and calculated with Konrad and the results obtained were compared with film measurements performed with radiographic films (EDR2, Kodak). Additionally, measurements were performed with point detectors, such as diamond, diodes (PTW) and ionization chambers (PTW, Scanditronics/ Wellhöfer) and radiochromic films (GafChromic film MD55, ISP). RESULTS: The results obtained with all three 2-D detector systems were in good agreement with calculations performed with the treatment-planning system and with the standard dosimetric tools, i.e., films or various point dose detectors. It could be shown that all three systems offer dosimetric characteristics required for performing field-related IMRT QA with relative dose measurements. The accuracy of the 2-D detectors was mostly +/- 3% normalized to dose maximum for a wide dynamic range. The maximum deviations did not exceed +/- 5% even in regions with a steep dose gradient. The main differences between the detector systems were the spatial resolution, the maximal field size, and the ability to perform absolute dosimetric measurements. CONCLUSION: Commercial 2-D detectors have the potential to replace films as an "area detector" for field-related verification of IMRT. The on-line information provided by the respective systems can even improve the efficiency of the QA procedures.

Germany↗

PubMed2003

Molecular whole-body cancer staging using positron emission tomography: consequences for therapeutic management and metabolic radiation treatment planning.

A prospective analysis was performed in 124 non-small cell lung cancer patients to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring after induction-chemotherapy (n=34), and conformal radiation treatment planning (n=27). Staging by FDG-PET was significantly more accurate than CT (p<0.001) and changed therapeutic management in 52% of all patients. After induction-chemotherapy, patients with complete metabolic remission histologically did not show vital tumor cells in contrast to patients with metabolic partial remission or progressive disease. Metabolic radiation treatment planning by PET led to smaller planning target volumes (PTVs) for radiation therapy (between 3% and 21% in 25/27 patients), resulting in a reduction of dose exposure to healthy tissue. In two patients, PET-PTV was larger than CT-based PTV, since PET detected lymph node metastases smaller than 1 cm. FDG-PET provides clinically important information; changes therapeutic management, can predict noninvasively effectiveness of chemotherapy, and may lead to better tumor control with less radiation-induced toxicity.

Disease Progression↗

PubMed2003

[Improved patient repositioning accuracy by integrating an additional jaw fixation into a high precision face mask system in stereotactic radiotherapy of the head].

BACKGROUND: For high precision radiotherapy of the neurocranium a precise, reproducible positioning technique is the basic prerequisite. The aim of this study was to assess the influence of a modification of the commercially available stereotactical BrainLab-head mask system on accuracy in patient positioning during fractionated radiotherapy. MATERIAL AND METHODS: 29 patients were treated with stereotactic radiotherapy of the head. Immobilization was provided by a two layer thermoplastic mask system (BrainLab). 18 of these patients received an additional custom made fixation either of the upper jaw (OKF) or of the mandibula (UKF). The positioning accuracy was assessed by measurements of the shifting of anatomical landmarks in relation to the rigid mask system on biplanar simulator films using a digital imaging system. Before each measurement a fine adjustment of the simulator to an optical ring system was performed. The reference radiographs were done just before CT-planning. During a 2-7 weeks lasting course of radiotherapy displacement measurements in relation to the reference images for all three dimensions (z, y and x) were done once a week. In 29 patients 844 measurements were analyzed. RESULTS: An additional jaw fixation improves the reproducibility of patient positioning significantly in all three spatial dimensions. The standard deviation in lateral direction (x) was 0.6 mm with jaw fixation vs. 0.7 mm without jaw fixation (p < 0.001); in longitudinal direction (z) (measured in 0 degree radiographs) 0.5 mm vs. 1.3 mm (p < 0.001); in longitudinal direction (measured in 90 degrees radiographs) 0.5 mm vs. 1.5 mm (p < 0.001); in vertical direction (y) 0.6 mm vs. 0.9 mm (p = 0.001). No significant differences in standard deviations were found comparing OKF (n = 14) with UKF (n = 4). CONCLUSION: A significant improvement in reposition accuracy using an additional, individually formed jaw fixation can be acquired. The variability of positioning can be reduced especially in the z-direction. A further reduction of the safety margin around the target volume--especially in benign tumors--is possible by improved fixation technique.

Brain Neoplasms↗

PubMed2003

Residual chromosomal damage after radiochemotherapy with and without amifostine detected by 24-color FISH.

BACKGROUND: Amifostine is a radioprotective drug applied to reduce acute radiation toxicity during a course of conventionally fractionated radiotherapy. In the present study, amifostine was used in patients undergoing adjuvant radiochemotherapy for rectal cancer. It was described previously that additional application of amifostine led to less acute skin and bowel toxicity. The present study was aimed to determine whether amifostine has an influence on the amount of residual chromosomal damage. MATERIAL AND METHODS: Peripheral lymphocytes of twelve rectal cancer patients who had undergone postoperative radiochemotherapy 2-3 years ago were investigated for residual chromosomal damage using 24-color fluorescence in situ hybridization (24-color FISH). All twelve patients had received a total dose of 55.8 Gy in conventional fractionation of 1.8 Gy and a 120-h continuous infusion of 5-fluorouracil (5-FU) chemotherapy (1,000 mg/m(2) per day) in the 1st and 5th week of irradiation. Seven out of twelve patients had been given additional amifostine on chemotherapy days (500 mg total dose as short i.v. infusion immediately prior to the daily radiation fraction). Cultivation of lymphocytes and 24-color FISH were performed according to standard protocols. 100 metaphases per patient were analyzed for chromosomal aberrations in a blind study. RESULTS: Analysis of the average number of breaks per mitosis (B/M) revealed an increased amount of residual chromosomal damage in the group treated with amifostine (0.65 B/M [0.32-0.97]) as well as in those treated without amifostine (0.76 B/M [0.31-1.25]). Also the average number of cells containing aberrations per 100 analyzed metaphases was similar (with amifostine: 22.1 [13-32] vs. 24.4 [13-35] without amifostine). The aberration types, occurring as simple translocations, reciprocal translocations, breaks, dicentrics, inversions, rings and complex chromosomal rearrangements, did not show any specific accumulation in one or the other group either. CONCLUSION: While there was a significant amifostine-mediated clinical amelioration of normal tissue toxicity, the comparison of residual chromosomal damage 2-3 years after completion of radiochemotherapy was characterized by a high interindividual variation, and no equivalent difference could be detected between the two groups.

Aged↗

PubMed2003

[Improvement of the accuracy of the Laplace transform method for the determination of radiotherapy spectra of clinical linear accelerators].

The present study focused on the reconstruction of the bremsstrahlung spectrum of a clinical linear accelerator from the measured transmission curve, with the aim of improving the accuracy of this method. The essence of the method was the analytic inverse Laplace transform of a parameter function fitted to the measured transmission curve. We tested known fitting functions, however they resulted in considerable fitting inaccuracy, leading to inaccuracies of the bremsstrahlung spectrum. In order to minimise the fitting errors, we employed a linear combination of n equations with 2n-1 parameters. The fitting errors are now considerably smaller. The measurement of the transmission function requires that the energy-dependent detector response is taken into account. We analysed the underlying physical context and developed a function that corrects for the energy-dependent detector response. The factors of this function were experimentally determined or calculated from tabulated values.

Models, Theoretical↗

PubMed2002

Microscopic evidence for a minus-end-directed power stroke in the kinesin motor ncd.

We used cryo-electron microscopy and image reconstruction to investigate the structure and microtubule-binding configurations of dimeric non-claret disjunctional (ncd) motor domains under various nucleotide conditions, and applied molecular docking using ncd's dimeric X-ray structure to generate a mechanistic model for force transduction. To visualize the alpha-helical coiled-coil neck better, we engineered an SH3 domain to the N-terminal end of our ncd construct (296-700). Ncd exhibits strikingly different nucleotide-dependent three-dimensional conformations and microtubule-binding patterns from those of conventional kinesin. In the absence of nucleotide, the neck adapts a configuration close to that found in the X-ray structure with stable interactions between the neck and motor core domain. Minus-end-directed movement is based mainly on two key events: (i) the stable neck-core interactions in ncd generate a binding geometry between motor and microtubule which places the motor ahead of its cargo in the minus-end direction; and (ii) after the uptake of ATP, the two heads rearrange their position relative to each other in a way that promotes a swing of the neck in the minus-end direction.

Adenosine Diphosphate↗

PubMed2002

Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity?

BACKGROUND: Reliable determination of intrinsic radiosensitivity in individual patients is a serious need in radiation oncology. Chromosomal aberrations are sensitive indicators of a previous exposure to ionizing irradiation. Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. However, only one up to three randomly chosen wcp probes have been applied for such approaches until now. As a random distribution of chromosomal rearrangements along the chromosomes is up to now still controversial, the power of the 24-color FISH approach should be elucidated in the present study. METHODS AND MATERIAL: Lymphocytes derived from lymphoblastoid cell lines of one patient with Nijmegen breakage syndrome (NBS homozygote) and of two NBS heterozygotes and peripheral blood lymphocytes of two controls were analyzed. Samples of each patient/control were irradiated in vitro with 0.0 Gy, 0.7 Gy or 2.0 Gy prior to cultivation. Chromosomal aberrations were analyzed in detail and quantified by means of 24-color FISH as an expression of the individual intrinsic radiosensitivity. RESULTS: 24-color FISH analyses were done in a total of 1,674 metaphases. After in-vitro irradiation, 21% (0.7 Gy) or 57% (2.0 Gy) of the controls' cells, 15% (0.7 Gy) or 53% (2.0 Gy) of the heterozygotes' cells and 54% (0.7 Gy) or 79% (2.0 Gy) of the homozygote's cells contained aberrations. The highest average rates of breaks per mitosis [B/M] (0.7 Gy: 1.80 B/M, 2.0 Gy: 4.03 B/M) and complex chromosomal rearrangements [CCR] (0.7 Gy: 0.20 CCR/M, 2.0 Gy: 0.47 CCR/M) were observed in the NBS patient. Moreover, the proportion of different aberration types after irradiation showed a distinct increase in the rate of CCR combined with a decrease in dicentrics in the NBS homozygote. CONCLUSION: To come to a more complete picture of radiation-induced aberrations and to detect and quantify genetically determined intrinsic radiosensitivity, a 24-color FISH approach using all human chromosome painting probes has been successfully applied on cytogenetic preparation lymphocytes. The controls and NBS heterozygotes were clearly distinguished from the NBS homozygote subject.

Adult↗

PubMed2002

VERIDOS: a new tool for quality assurance for intensity modulated radiotherapy.

BACKGROUND: The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. MATERIAL AND METHODS: The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. RESULTS: VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. CONCLUSIONS: VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology).

Dose Fractionation, Radiation↗

PubMed2002

[Intensity modulated radiotherapy (IMRT) with compensators].

The irradiation with intensity-modulated fields is possible with static as well as dynamic methods. In our university hospital, the intensity-modulated radiotherapy (IMRT) with compensators was prepared and used for the first time for patient irradiation in July 2001. The compensators consist of a mixture of tin granulate and wax, which is filled in a milled negative mould. The treatment planning is performed with Helax-TMS (MDS Nordion). An additional software is used for editing the modulation matrix ("Modifix"). Before irradiation of the first patient, extensive measurements have been carried out in terms of quality assurance of treatment planning and production of compensators. The results of the verification measurements have shown that IMRT with compensators possesses high spatial and dosimetric exactness. The calculated dose distributions are applied correctly. The accuracy of the calculated monitor units is normally better than 3%; in small volumes, further dosimetric inaccuracies between calculated and measured dose distributions are mostly less than 3%. Therefore, the compensators contribute to the achievement of high-level IMRT even when apparatuses without MLC are used. This paper describes the use of the IMRT with compensators, presents the limits of this technology, and discusses the first practical experiences.

Equipment Design↗