Search PubMed⌕ Search

Biomedical subjects

Michael Baumann

Publications and source records attributed to Michael Baumann.

52 records · Page 3Linked to original sources
PubMed2003

Physical and technical quality assurance in the CHARTWEL-Bronchus trial.

BACKGROUND: On-site physical quality assurance (QA) was performed in the participating centers of the CHARTWEL-Bronchus trial to ensure that physical and technical treatment parameters correspond with the requirements of this trial. MATERIAL AND METHODS: Questionnaires were sent to the clinics to obtain information on the equipment and in-house QA policies. In addition, two phantoms with drillings for an ionization chamber were shipped with detailed instructions for CT-based treatment planning of a fixed field (RW3 phantom) and a standardized isocentric 3-field technique (Rando humanoid phantom). Using their routine treatment planning system, the participating centers performed point dose calculations for the isocenters in both phantoms and for defined points in the lungs and the spinal cord of the Rando phantom. During the on-site visit, the doses in these points and the deviation of the actual monitor calibration from the internal reference value of the department were determined. In addition, relevant geometric parameters of the accelerator were checked. RESULTS: In the RW3 phantom, the maximum dose deviations from the prescribed value were 3.5% without correction for the actual monitor calibration and 2.1% after correction. The maximum dose deviation in the isocenter of the Rando phantom was 4.0%. To separate the influence of the treatment planning system on this deviation from other sources, all measurements in the Rando phantom were corrected for the deviations determined in the RW3 phantom. After this correction, the maximum deviation was 3.0% in the isocenter. For the other measurement points, the largest dose deviation of 7% was found in the left lung. Deviations of geometric parameters were negligible in all audited departments. CONCLUSION: The CHARTWEL-Bronchus physical QA program revealed a high conformity of geometric and dosimetric parameters and valid dose calculations by the CT-based treatment planning systems in all audited departments.

Humans↗
PubMed2003

Selection of genetically distinct, rapidly proliferating clones does not contribute to repopulation during fractionated irradiation in FaDu squamous cell carcinoma.

Acceleration of clonogen repopulation during fractionated irradiation after about 3 weeks has been demonstrated previously in FaDu human squamous cell carcinoma in nude mice (Petersen et al., Int. J. Radiat. Oncol. Biol. Phys. 51, 483-493, 2001). Selection of genetically distinct, rapidly proliferating clones might contribute to this phenomenon. To address this question, three sublines (R1-R3) were established from FaDu tumors that recurred locally after fractionated irradiation. The tumors were retransplanted and irradiated under clamp hypoxia with single doses or with 18 x 3 Gy within 18 days or 36 days, followed by graded top-up doses. The results were compared with data obtained after the same treatment schedules in the parental tumor line. Histologies, tumor volume doubling times, and potential doubling times of FaDu sublines R1-R3 were not different from those of the parental line. The radiation dose required to control 50% of the tumors (TCD(50)) after single-dose irradiation of 37-38 Gy was the same for the FaDu sublines R1-R3 and the parental tumor. The top-up TCD(50) values for the FaDu sublines R1-R3 after 18 fractions within 36 days were 14-17 Gy higher than those after 18 fractions within 18 days, indicating significant repopulation. The magnitude of this effect was not significantly different between the sublines R1-R3 or between these sublines and the parental FaDu tumors. The results indicate that selection of genetically distinct, rapidly proliferating clones does not contribute to the acceleration of repopulation during fractionated irradiation in poorly differentiated FaDu tumors.

Animals↗
PubMed2003

New targets for the modulation of radiation response--selective inhibition of the enzyme cyclooxygenase 2.

The development of new chemotherapeutic agents and concepts of radiation therapy has led to new perspectives in cancer therapy. Recently developed novel agents interfere with molecular mechanisms that are altered in cancer cells. Cyclooxygenase-2 (COX-2) is an enzyme induced by a variety of factors including tumor promoters, cytokines, growth factors and hypoxia. It is involved in the metabolic conversion of arachidonic acid to prostanoids, primarily in inflammatory states and tumors. In normal tissues, prostanoids are synthesized by COX-1, and they exert numerous homeostatic physiological functions. COX-2 overexpression is linked to carcinogenesis, maintenance of progressive tumor growth and metastatic spread. COX-2 and its products may act as protectors against cell damage by ionizing radiation. In this context, the treatment with selective COX-2 inhibitors became of interest for radiation oncology within the last years. In this review we focus on the effects of COX-2 in the modulation of the radiation response and the potential clinical application as cancer preventive drug or as novel agents in adjuvant clinical settings. The experimental data available suggest that COX-2 inhibitors can enhance the radiation response in tumors without serious side effects to the normal tissue. In conclusion COX-2 might be a useful tool for cancer prevention and represents a potential molecular target for improving cancer treatment in combination with radiotherapy.

Animals↗
PubMed2003

Technologies for haptic systems in telemedicine.

The ability to image the elastic properties of tissue is potentially useful in a variety of applications. The field of elastic imaging has grown in response to the potential use of such information in medical diagnosis. Real time ultrasound elastography represents a recent development in determining strain and elasticity distributions. Nevertheless, commonly used imaging techniques rely on the interpretation of two dimensional visual data displayed on a video screen. In reality however, physicians often prefer tactile exploration making the simultaneous portrayal of both video and haptic information most desirable. Since the 1970's many alphanumeric to tactile data conversion methods have been investigated, mainly with the ultimate aim of assisting the blind. More recently, interest has been directed toward the display of pictures on haptically explorable surfaces--Tactile imaging. Such a system would allow surgeons to examine hard sectors contained within soft tissue, and thereby assist in operations held remotely. The expansion of ultrasound elastography to 3D formats would mean the ability to haptically explore regions of the body normally inaccessible to human hands. For three-dimensional imaging the acquisition of sequential tomographic slices using Elastography, combined with image segmentation, enables the reconstruction, quantification and visualisation of tumour volumes. In a collaborative project between four research institutes, the aim is to produce a prototype three dimensional tactile displays comprising electrically switchable micromachined cells, whose mechanical moduli are governed by phase changes experienced by electrorheological and/or magnetorheological fluids. This will be integrated with a sensory ultrasonic elastography in order to present the human fingers with controllable surfaces capable of emulating biological tissue, muscle and bone.

Computer Simulation↗
PubMed2002

Immunohistochemically detected p53 mutations in epithelial tumors and results of treatment with chemotherapy and radiotherapy. A treatment-specific overview of the clinical data.

BACKGROUND: The aim was to ascertain whether many hundreds of clinical reports over the last decade are consistent with the prediction of a poorer outcome in cancer patients with p53 abnormalities treated with cytotoxic drugs and radiation. MATERIAL AND METHOD: There are 301 studies on the influence of p53 overexpression published through summer 2000, in which chemotherapy or radiotherapy was used alone or in combination with surgery. From 45 reports meeting stringent selection rules, comparison groups are identified in whom the same measure of outcome was reported for the same treatment applied to the same tumor, with results corrected for important prognostic factors. Metaanalysis techniques are then applied to the comparison groups. Attention was limited to reports using immunohistochemical techniques, to form comparison groups of sufficient size. RESULTS: Four comparison groups were identified by treatment and endpoint: 1) Stage I-III breast cancer (surgery and chemotherapy, disease-free survival, seven studies); 2) stage I-III breast cancer (surgery and chemotherapy, overall survival, six studies); 3) stage II-IV head and neck cancer (radiotherapy and chemotherapy, overall survival, five studies); 4) FIGO I-IV ovarian cancer (surgery and chemotherapy, overall survival, six studies). In the breast (disease-free survival) and ovarian (overall survival) comparison groups, the hazard ratio for a deleterious effect of p53 overexpression was significant or marginally significant, depending on assumed ranges for unreported hazard ratios in non-significant studies. CONCLUSIONS: Despite the many caveats related to metaanalysis applied to retrospective data, high variability of immunohistochemical technique, etc., a nearly significant negative effect of p53 overexpression on outcome of treatment with cytotoxic drugs and radiation emerges in the few studies where heterogeneity can be sufficiently reduced or accounted for.

Analysis of Variance↗
PubMed2002

2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography in target volume definition for radiotherapy of patients with non-small-cell lung cancer.

PURPOSE: To discuss the potential contribution of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) in radiotherapy planning for non-small-cell lung cancer (NSCLC) considering new concepts on target volume definition. PROCEDURES: Recent investigations on the topic are reviewed with regard to current concepts of target volume definition for NSCLC. RESULTS: As intrathoracic recurrence is the leading cause of death after primary radiotherapy of NSCLC, there is a need for improving local control by escalating treatment intensity to gross disease. The value of elective nodal irradiation (ENI), resembling prophylactic irradiation of macroscopically unaffected parts of the mediastinum, is being considered. CONCLUSION: As FDG-PET has been shown to enhance the diagnostic accuracy of computed tomography (CT), and to have a potentially high impact on the identification of malignant tissue, it should be implicated in prospective clinical trials on dose escalation and three-dimensional conformal radiotherapy, especially in those including a reduction of target volumes.

Journal Article↗
PubMed2002

Splicing mutations in TP53 in human squamous cell carcinoma lines influence immunohistochemical detection.

The mutational status of the tumor suppressor gene TP53 is often examined by immunohistochemistry. We compared the incidence of TP53 mutations in 12 permanent squamous cell carcinoma lines of the head and neck with the immunohistochemical staining obtained with two different antibodies. The mutational status of the TP53 gene was assessed by sequencing the complete coding frame of the TP53 mRNA. All 12 tumor cell lines had TP53 mutations. Six of them showed missense mutations and five had premature stop codons caused either by splicing mutations or nonsense mutations or by exon skipping. One tumor cell line was heterozygous, with a truncating splicing mutation and an additional missense mutation located on different alleles. In one case, an in-frame insertion of 23 extra codons was found. All missense mutations were positive in immunhistochemistry and Western blotting. The truncated p53 was not immunohistochemically detected in three cases with the DO-7 antibody and in five cases with the G59-12 antibody, giving false-negative results in 25% or 40%, respectively, of all tumor cell lines examined. We conclude that splicing mutations are common in squamous cell carcinoma lines and that the incidence of p53 inactiviation by erroneous splicing is higher than yet reported. Sequencing of only the exons of TP53 may miss intronic mutations leading to missplicing and may therefore systematically underestimate the TP53 mutation frequency.

Animals↗
PubMedDate not supplied

Experimental study on different combination schedules of VEGF-receptor inhibitor PTK787/ZK222584 and fractionated irradiation.

BACKGROUND: Inhibition of the vascular endothelial growth factor receptor (VEGFR) has been shown to improve the radiation response of several experimental tumors. The present experimental study compares the effect of neoadjuvant, concomitant and adjuvant treatment with PTK787/ZK222584, a specific inhibitor of the VEGFR, in combination with fractionated irradiation. MATERIALS AND METHODS: Growth delay after daily oral application of 50 mg per kg bodyweight PTK787/ZK222584 or carrier was tested in five different human squamous cell carcinoma growing in nude mice. Two of these tumor models, a responder (UT-SCC-14) and a non-responder (FaDu), were selected for the irradiation experiments (15 fractions of 2 Gy within 15 days). PTK787/ZK222584 was applied daily for 4-18 days and stopped before start of irradiation (neoadjuvant), for 15 days during fractionated irradiation (concomitant) or for 45 days after the course of irradiation (adjuvant). RESULTS: Adjuvant application of PTK787/ZK222584 after fractionated irradiation retarded regrowth of UT-SCC-14 tumors and, surprisingly, also of FaDu tumors which did not respond to the agent when given alone. No effects on radiation response were observed after short-term neoadjuvant or concomitant PTK787/ZK222584 application. CONCLUSION: Combined with fractionated irradiation, only adjuvant application of PTK787/ZK222584 retarded regrowth of UT-SCC-14 and FaDu tumors. The data suggest that preirradiated vasculature might be more sensitive to VEGFR inhibition compared to unirradiated vasculature. Whether the effect of adjuvant VEGFR inhibition on growth delay translates into improved local tumor control after irradiation needs further investigation.

Angiogenesis Inhibitors↗
PubMedDate not supplied

New anticancer agents: in vitro and in vivo evaluation.

The rapid emergence of new anticancer agents is a tremendous challenge for basic, pre-clinical and clinical research to evaluate and eventually integrate these new agents into clinical routine. Standardized, well-established in vitro and in vivo methods are available for the experimental evaluation of new anticancer agents. A step-wise procedure from in vitro to in vivo experiments using non-functional, functional non-clonogenic and, if applicable, clonogenic assays allows reduction of the number of promising agents for further clinical testing.

Animals↗
PubMedDate not supplied

TCP and NTCP: a basic introduction.

Radiotherapy is one of the most effective treatments for cancer. The aim of radiotherapy is to achieve a high probability of local tumor control (tumor control probability, TCP) at a low risk of normal tissue complications (normal tissue complication probability, NTCP). This paper gives a brief introduction into dose response relationships for early and late radiation responses and tumor control. The impact of basic parameters of the fractionation schedules on these responses is described. Easy examples illustrate how Poisson statistics can be used to understand dose-response relationships in radiotherapy.

Dose Fractionation, Radiation↗
PubMedDate not supplied

TCP and NTCP in preclinical and clinical research in Europe.

European research in radiation oncology has a long and successful tradition. The aim of this research is to increase the therapeutic window of radiotherapy by increasing the tumor control probability (TCP) and/or by decreasing the normal tissue complication probability (NTCP). This paper summarizes the basic radiobiological concept underlying treatment optimization by TCP-NTCP data and discusses some of the limitations of currently used models. These are controversial in many aspects and cannot be recommended for clinical routine practice but should rather be considered as a research tool.

Animals↗