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  • 1
    Keywords: CANCER ; radiotherapy ; SURVIVAL ; carcinoma ; CELL ; Germany ; LUNG ; THERAPY ; CT ; FOLLOW-UP ; lung cancer ; LUNG-CANCER ; DISEASE ; incidence ; MORTALITY ; TIME ; PATIENT ; INDEX ; RISK-FACTORS ; tumour ; PERFORMANCE ; STAGE ; EXPERIENCE ; AGE ; CIGARETTE-SMOKING ; MEN ; arteries ; PROGNOSTIC-FACTORS ; DELIVERY ; PROGNOSTIC FACTORS ; TOBACCO ; ARTERY ; CONSUMPTION ; SMOKERS ; PROGNOSTIC FACTOR ; AORTIC ATHEROSCLEROSIS ; CARDIOVASCULAR-DISEASES ; COMORBIDITY ; non-small cell lung cancer ; STAGE-I
    Abstract: It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI〈90% had a median survival of 6.5 months compared with 14 months, in patients with KIgreater than or equal to90% (p〈0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p〈0.004). A significant correlation was seen between pack-years and coronary artery calcification (p〈0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (greater than or equal to20 pack-years) and 43/58 in patients 〉60 years (p〈0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival
    Type of Publication: Journal article published
    PubMed ID: 14711777
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  • 2
    Keywords: measurement ; Germany ; LUNG ; TIME ; PATIENT ; QUALITY ; BODY-WEIGHT ; CONTRAST ; INJECTION ; MAGNETIC-RESONANCE ; DIFFERENCE ; RATES ; arteries ; VASCULATURE ; GADOPENTETATE DIMEGLUMINE ; MAGNETIC-RESONANCE ANGIOGRAPHY ; gadobenate dimeglumine ; ARTERIOVENOUS-MALFORMATION ; lung,magnetic resonance angiography,comparative study,contrast agent,time-resolved
    Abstract: Purpose: To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd-DTPA for time-resolved three-dimensional pulmonary magnetic resonance angiography (MRA).Materials and Methods: Thirty-one patients and five healthy volunteers were examined with a contrast-enhanced time-resolved pulmonary MRA protocol (fast low-angle shot [FLASH] three-dimensional, TR/TE=2.2/1.0 msec, flip angle: 25degrees, scan time per three-dimensional data set=5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd-DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol. using two different flip angles and once with 0.2 mmol/kg bw Gd-DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal-to-noise ratio (SNR) and contrast-to-noise. ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality.Results: In patients, significantly higher SNR and CNR were observed with Gd-DTPA compared to both doses of gadobutrol (SNR: 35-42 vs. 17-25; CNR 33-39 vs. 16-23; Pless than or equal to0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd-DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol-enhanced MRA with an increased flip angle of 40degrees. Image quality was rated equal for both contrast agents.Conclusion: No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd-DTPA were observed for time-resolved pulmonary MRA in this study. Potential explanations are T2/T2*-effects caused by the high intravascular concentration when using high injection rates
    Type of Publication: Journal article published
    PubMed ID: 14745754
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  • 3
    Keywords: CANCER ; tumor ; carcinoma ; Germany ; LUNG ; PERFUSION ; THERAPY ; CT ; DENSITY ; LUNG-CANCER ; NEW-YORK ; TUMORS ; PATIENT ; CONTRAST ; INJECTION ; treatment ; DIFFERENCE ; REGION ; REGIONS ; LOCALIZATION ; PARAMETERS ; tomography ; CARCINOMAS ; COMPUTED-TOMOGRAPHY ; PET ; lung neoplasms ; PULMONARY ; DYNAMIC CT ; X-ray computed
    Abstract: Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (I scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (〉50 cm(3)) averaged over both the whole tumor (P=0.001) and the highest enhancing area (P=0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P=0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 9). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors
    Type of Publication: Journal article published
    PubMed ID: 15029450
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  • 4
    Keywords: radiotherapy ; SURVIVAL ; Germany ; THERAPY ; FOLLOW-UP ; VOLUME ; NEW-YORK ; radiation ; PATIENT ; CONTRAST ; MR ; MRI ; treatment ; stereotactic ; stereotactic radiotherapy ; RADIATION-THERAPY ; RATES ; PROGNOSTIC FACTORS ; RANDOMIZED TRIAL ; ONCOLOGY-GROUP ; POSTOPERATIVE RADIOTHERAPY ; ADULTS ; BRAIN-TUMORS ; CONTRAST ENHANCEMENT ; GLIOMA ; GRADE ; LOW-GRADE ASTROCYTOMA ; astrocytoma,MRI,prognosticator,stereotactic radiotherapy
    Abstract: Aim of this study was to evaluate the role of pre-therapeutic and follow-up MRI in the clinical treatment and outcome in patients with astrocytoma WHO grade II after fractionated stereotactic radiation therapy (FSRT). One hundred thirty-nine patients with histologically proven astrocytoma WHO grade II were treated with FSRT and retrospectively evaluated. All patients had follow-up MRI studies (Gd-DTPA-enhanced T1- and T2-weighted MR images). Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed on five potential MRI related prognosticators. Median follow-up was 3.8 years. Positive contrast enhancement (CM+) prior to FSRT proved to be a significant prognosticator for PFS and OS (p〈0.01). Pre-therapeutic oedema on T2-weighted images and multifocality of contrast medium (CM) enhancement did not prove to be significant prognosticators. Also, diameter and volume of CM enhancement showed no significance on clinical outcome. Negative contrast enhancing (CM-) patients developing a de novo CM enhancement during follow-up showed a significantly worse clinical outcome compared with generally CM- patients (p〈0.05). Pre-therapeutic CM enhancement and the development of CM-enhancing areas during follow-up are negative prognosticators for PFS and OS. They must be interpreted as signs of secondary malignity
    Type of Publication: Journal article published
    PubMed ID: 14610685
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  • 5
    Keywords: evaluation ; Germany ; LUNG ; MODEL ; CT ; EMPHYSEMA ; imaging ; TOOL ; DISEASE ; MRI ; CYCLE ; SEQUENCE ; INVIVO ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; PARAMETERS ; MOTION ; PULMONARY ; TRUEFISP ; HEALTHY-VOLUNTEERS ; EXPIRATION ; HUMAN DIAPHRAGM SHAPE ; INSPIRATORY PUMP ; lung dynamic,magnetic resonance imaging,respiration,model,spirometry ; LUNG-VOLUMES ; WALL MECHANICS
    Abstract: Rationale and Objectives: To investigate diaphragm and chest wall motion during the whole breathing cycle using magnetic resonance imaging (MRI) and a volumetric model in correlation with spirometry.Materials and Methods: Breathing cycles of 15 healthy volunteers were examined using a trueFISP sequence (5 slices in 3 planes, 3 images per second). Time-distance curves were calculated and correlated to spirometry. A model for vital capacity (VC), continuous time-dependent vital capacity (tVC), and investigating the influence of horizontal and vertical parameters on tVC was introduced.Results: Time-distance curves of the breathing cycle using MRI correlated highly significant with spirometry (P 〈 0.0001). VC calculated by the model was similar to VC measured in spirometry (5.00 L vs. 5.15 L). tVC correlated highly significantly with spirometry (P 〈 0.0001). Vertical parameters had a more profound influence on tVC change than horizontal parameters.Conclusions: Dynamic MRI is a simple noninvasive method to evaluate local chest wall motion and respiratory mechanics. It widens the repertoire of tools for lung examination with a high temporal resolution
    Type of Publication: Journal article published
    PubMed ID: 15021323
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  • 6
    Keywords: measurement ; CANCER ; radiotherapy ; tumor ; Germany ; LUNG ; IMAGES ; lung cancer ; LUNG-CANCER ; TISSUE ; TUMORS ; PATIENT ; MRI ; CYCLE ; SEQUENCE ; STAGE ; RADIATION-THERAPY ; MOBILITY ; REGION ; REGIONS ; WALL ; CURVES ; MOTION ; FUTURE ; LINEAR-ACCELERATOR ; LOCATION ; dynamic MRI ; TRUEFISP ; PULMONARY-FUNCTION ; EXTERNAL-BEAM RADIOTHERAPY ; breathing cycle ; CT SCANS ; DIAPHRAGM ; HEALTHY-SUBJECTS ; lung MRL radiotherapy ; tumor diameter
    Abstract: Background and purpose: To assess the influence of tumor diameter on tumor mobility and motion of the tumor bearing hemithorax during the whole breathing cycle in patients with stage I non-small-cell lung cancer (NSCLC) using dynamic MRI. Patients and methods: Breathing cycles of thirty-nine patients with solitary NSCLCs were examined using a trueFISP sequence (three images per second). Patients were divided into three groups according to the maximal tumor diameter in the transverse plane ( 〈3, 3-5 and 〉5 cm). Continuous time-distance curves and deep inspiratory and expiratory positions of the chest wall, the diaphragm and the tumor were measured in three planes. Motion of tumor-bearing and corresponding contralateral non-tumor bearing regions was compared. Results: Patients with a tumor 〉3 cm showed a significantly lower diaphragmatic motion of the tumor bearing compared with the non-tumor bearing hemithorax in the craniocaudal (CC) directions (tumors 3-5 cm: 23.4 +/- 1.2 vs 21.1 +/- 1.5 cm (P 〈0.05); tumors 〉5 cm: 23.4 +/- 1.2 vs 20.1 +/- 1.6 cm (P 〈0.01). Tumors 〉5 cm in the lower lung region showed a significantly lower mobility compared with tumors 〈3 cm (1.8 +/- 1.0 vs 3.8 +/- 0.7 cm, P 〈0.01) in the CC directions. Conclusions: Dynamic MRI is a simple non-invasive method to differentiate mobility of tumors with different diameters and its influence on the surrounding tissue. Tumor diameter has a significant influence on tumor mobility and this might be taken into account in future radiotherapy planning, (C) 2004 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15588881
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  • 7
    Keywords: brain ; OPTIMIZATION ; BLOOD ; Germany ; CT ; DENSITY ; IMAGES ; EXPOSURE ; radiation ; CONTRAST ; X-RAYS ; COMPUTED-TOMOGRAPHY ; CT ANGIOGRAPHY ; contrast media ; BLOOD-VESSELS ; ENHANCEMENT ; cerebral angiography ; IMAGE QUALITY ; spiral computed tomography
    Abstract: Purpose: We sought to intraindividually compare computed tomography angiographies (CTAs) acquired at 80 kVp and 120 kVp with respect to vessel contrast, noise level, and radiation dose. Material and Methods: CTA was performed on a single-slice CT scanner using tube voltages of 80 kVp and 120 kVp in 29 patients with arteriovenous malformations. Mean Hounsfield Units (HU) were evaluated for different vessels and brain parenchyma. To determine contrast-to-noise ratios (CNRs), noise levels were estimated from phantom measurements. Results: The calculated effective dose to male/female patients was 0.4/0.5 mSv for 80 kVp and 0.7/0.8 mSv for 120 kVp. CT density in blood vessels was between 297 and 458 HU for 80 kVp and 152 and 229 HU for 120 kVp (P 〈 0.0001). Despite an increased noise level in the low-voltage images, the CNR was 26-59% higher at 80 kVp than at 120 kVp (P 〈 0.05). Conclusion: The use of a reduced tube potential leads to improved CNR in CTA of the cerebral vasculature and a markedly reduced radiation exposure to patients
    Type of Publication: Journal article published
    PubMed ID: 15770141
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  • 8
    Keywords: brain ; measurement ; radiotherapy ; tumor ; BLOOD ; Germany ; PERFUSION ; THERAPY ; FOLLOW-UP ; follow-up studies ; imaging ; QUANTIFICATION ; VOLUME ; TISSUE ; NUCLEAR-MEDICINE ; radiation ; PATIENT ; BLOOD-FLOW ; blood flow ; FLOW ; MRI ; SEQUENCE ; treatment ; stereotactic ; radiosurgery ; STEREOTACTIC RADIOSURGERY ; DECREASE ; metastases ; CEREBRAL-BLOOD-FLOW ; PREDICTION ; NORMAL TISSUE ; nuclear medicine ; brain metastases ; GLIOMAS ; LOBE EPILEPSY ; QUIPSS-II ; radiology ; RE ; THERAPIES ; IMAGING TECHNIQUES ; TUMOR VOLUME ; ARTERIAL ; neoplasm metastasis ; relative regional cerebral blood flow ; VOLUME MAPS
    Abstract: Rationale and Objectives: To assess if preradiation and early follow-up measurements of relative regional cerebral blood flow (rrCBF) can predict treatment outcome in patients with cerebral metastases and to evaluate rrCBF changes in tumor and normal tissue after stereotactic radiosurgery using arterial spin-labeling (ASL) and first-pass dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI. Methods: In 25 patients with a total of 28 brain metastases, DSC MRI and ASL perfusion MRI using the Q2TIPS sequence were performed with a 1.5-T unit. Measurements were performed prior to and at 6 weeks. 12 weeks, and 24 weeks after stereotactic radiosurgery. Follow-up examinations were completely available in 25 patients for Q2TIPS and 17 patients with 18 metastases for DSC MRI. The rrCBF of the metastases and the normal brain tissue was determined by a region-of-interest analysis. rrCBF values were correlated with the treatment outcome that was classified according to tumor volume changes at 6 months. Results: The alteration of the rrCBF at the 6-week follow-up was highly predictive for treatment outcome. A decrease of the rrCBF value predicted tumor response correctly in all metastases for Q2TIPS and in 13 of 16 metastases for DSC MRI. The pretherapeutic rrCBF was not able to predict treatment outcome. The rrCBF values in normal brain tissue affected by radiation doses less than 0.5 Gy remained unchanged after therapy. Conclusion: These preliminary results suggest that ASL and DSC MRI techniques determining rrCBF changes in brain metastases after stereotactic radiosurgery allow the prediction of treatment outcome
    Type of Publication: Journal article published
    PubMed ID: 15087722
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  • 9
    Keywords: CELLS ; GROWTH ; IRRADIATION ; carcinoma ; Germany ; MODEL ; SYSTEM ; EXPOSURE ; radiation ; TIME ; DNA ; INDUCTION ; RAT ; RATS ; FLOW ; cell cycle ; CYCLE ; treatment ; BREAST-CANCER ; PROGRESSION ; CARCINOMAS ; DOSE-RATE BRACHYTHERAPY ; INITIATION ; CYCLE ARREST ; cell cycle progression ; animal model ; DOSE-RATE ; low dose rate brachytherapy ; prostate Dunning tumour ; pulsed dose rate brachytherapy ; RATE INTERSTITIAL BRACHYTHERAPY
    Abstract: Purpose: The study consisted of two treatment arms comparing the effects of CLDR (continuous low dose rate) and PDR ( pulsed dose rate) brachytherapy on cell cycle progression in a radioresistant rat prostate tumour model. Materials and methods: Interstitial PDR and CLDR brachytherapy ( both 192-Ir, 0.75 Gy/h) were administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to 40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell subpopulations were determined at 4 h ( 3 Gy), 24 h ( 18 Gy), 48 h ( 20 and 36 Gy), as well as during the subsequent redistribution period ( 20 and 40 Gy) at 72, 96, and 120 h. Tumours either implemented with an empty tubing system (n = 5) or under undisturbed growth (n = 5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. Results: The aneuploid cells possessed a constant DNA-Index of 1.9 +/- 0.06. In contrast to sham-treated controls, the aneuploid cell fraction with G2/M DNA content was significantly increased (p 〈 0.05) after initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p 〈 0.05) with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but then more pronounced cell cycle changes, particularly expressed during the redistribution period after both 20 and 40 Gy. Conclusion: CLDR and PDR brachytherapy showed differential effects on cell cycle progression. The induction of a significantly earlier but also less persistent G2/M cell cycle arrest after CLDR compared to PDR brachytherapy implies that a substantially higher fraction of tumour cells are irradiated in G2/M after CLDR
    Type of Publication: Journal article published
    PubMed ID: 16638716
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  • 10
    Keywords: PEPTIDE ; CANCER ; GROWTH ; tumor ; CELL ; CLINICAL-TRIAL ; INHIBITION ; MODEL ; PROSTATE ; REDUCTION ; RAT ; RATS ; T cell ; T-CELL ; SEQUENCE ; SUPPRESSION ; MOLECULE ; TRIAL ; TRIALS ; hormone ; CLINICAL-TRIALS ; prostate cancer ; PROSTATE-CANCER ; GROWTH-INHIBITION ; VACCINES ; VACCINE ; IMMUNOTHERAPY ; FUTURE ; PLASMODIUM-FALCIPARUM ; IMMUNIZATION ; CANCER VACCINES ; TUMOR-GROWTH ; END ; MURINE MODEL ; CARRIER ; TESTOSTERONE ; CANDIDATE ; immunology ; ANDROGEN ; HORMONE-RELEASING-HORMONE ; MEDICINE ; clinical trial ; ACTIVE IMMUNIZATION ; FERTILITY ; hormone-sensitive prostate cancer ; LHRH VACCINE ; REPRODUCTIVE-ORGANS
    Abstract: Previous studies with gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate cancer. To this end, we have generated a completely synthetic peptide modified at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence. Through this work we have demonstrated that the GnRHm1-TT molecule was highly immunogenic when it is formulated as an oil-based emulsion adjuvated with Montanide ISA 51. That results correlated directly with testosterone reduction and tumor growth inhibition of the Dunning R3327-H androgen responsive prostate tumor model in rats. GnRHm1-TT, proved to be safe and useful for future clinical trials. (c) 2007 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18022737
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