Patient Position Reproducibility in Fractionated Stereotactically Guided Conformal Radiotherapy Using the BrainLab? Mask System

Purpose: Dedicated mask systems nowadays allow the use of stereotactic radiotherapy in fractionated regimes, therefore combining the advantages of high precision radiotherapy with the biological benefit of fractionation. Therefore the knowledge of institution specific isocenter accuracy is essential for decision-making about margins to be allowed to form the planning target volume. Patients and Methods: Measurements of isocenter deviations during fractionated treatments were performed in 33 patients using the simulator Simulix-xy (Oldelft) in connection with the BrainLab^® angiographic localizer-box as well as port-films. In both cases repeated images were overlaid by use of anatomical landmarks with a methodical accuracy in the order of 0.5 mm. Results: Both methods yield random isocenter deviations of less then 2 mm (standard deviation) in all three directions and no significant systematic deviations. These values are in the order of the accuracy of the method, obtained by comparison of two independent investigators, as well as they are comparable with the literature. Conclusions: The accuracy of less than 2 mm indicates safety margins of 3-4 mm as sufficient for clinical routine to cover the target in 95.5% of all set-ups (2 SD). Ziel: Spezielle Maskensysteme erlauben heutzutage die Anwendung der stereotaktischen Strahlentherapie in fraktionierten Regimes und damit die Kombination der Vorteile der Hochpräzisionsbestrahlung mit dem biologischen Nutzen der Fraktionierung. Deshalb ist die Kenntnis der institutsspezifischen Genauigkeit der Isozentrumseinstellung eine notwendige Voraussetzung für die Entscheidung über die erforderlichen Sicherheitsabstände. Patienten und Methode: Die Messung der Isozentrumsgenauigkeit erfolgte bei 33 Patienten sowohl durch Simulatorkontrollen in Verbindung mit der BrainLab^®-Localizer-Box oder durch Verifikation mit Portfilmen. In beiden Fällen wurden die Filme anhand anatomischer Lankdmarken mit einer methodischen Sicherheit von unter 0,5 mm überlagert. Ergebnisse: Beide Methoden zeigten zufällige Isozentrumsabweichungen von weniger als 2 mm (Standardabweichung) in allen drei Raumebenen (Abbildung 1, Tabelle 2) und keine signifikanten systematischen Abweichungen. Damit liegen die Ergebnisse im Bereich der methodischen Genauigkeit, wie durch den Vergleich der Befunde zweier unabhängiger Untersucher gezeigt wird (Tabelle 1), und sind mit Literaturdaten gut vergleichbar. Schlussfolgerung: Die Genauigkeit von unter 2 mm zeigt, dass ein Sicherheitsabstand von 3-4 mm für die klinische Routine ausreichend ist, um bei 95,5% der Einstellung die sichere Erfassung des Targets zu garantieren.     

Patient Position Reproducibility in Fractionated Stereotactically Guided Conformal Radiotherapy Using the BrainLab® Mask System

PURPOSE: Dedicated mask systems nowadays allow the use of stereotactic radiotherapy in fractionated regimes, therefore combining the advantages of high precision radiotherapy with the biological benefit of fractionation. Therefore the knowledge of institution specific isocenter accuracy is essential for decision-making about margins to be allowed to form the planning target volume. PATIENTS AND METHOD: Measurements of isocenter deviations during fractionated treatments were performed in 33 patients using the simulator Simulix-xy (Oldelft) in connection with the BrainLab angiographic localizer-box as well as port-films. In both cases repeated images were overlaid by use of anatomical landmarks with a methodical accuracy in the order of 0.5 mm. RESULTS: Both methods yield random isocenter deviations of less then 2 mm (standard deviation) in all three directions and no significant systematic deviations. These values are in the order of the accuracy of the method, obtained by comparison of two independent investigators, as well as they are comparable with the literature. CONCLUSIONS: The accuracy of less than 2 mm indicates safety margins of 3-4 mm as sufficient for clinical routine to cover the target in 95.5% of all set-ups (2 SD).     

Lokale Tumorkontrolle und kosmetisches Ergebnis nach brusterhaltender Operation und Strahlentherapie bis 56 Gy Gesamtdosis ohne Boost beim Mammakarzinom

PURPOSE: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. PATIENTS AND METHODS: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. RESULTS: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. CONCLUSION: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results.     

Evaluation of Angiogenesis Using Micro-Computed Tomography in a Xenograft Mouse Model of Lung Cancer

Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, through the jugular vein (in vivo application) or pulmonary artery (ex vivo application). In addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically with humanized monoclonal antibody (bevacizumab) against vascular endothelial growth factor. Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm²) were filled using the in vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore, bevacizumab-treated lung tumor-bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT. Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm²) was reduced after bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis, and this might be considered as an additional complementary tool for precise quantification of angiogenesis.     

Imaging of integrin αvβ3 expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography

Inhibitors targeting the integrin α_vβ₃ are promising new agents currently tested in clinical trials for supplemental therapy of glioblastoma multiforme (GBM). The aim of our study was to evaluate ¹⁸F-labeled glycosylated Arg-Gly-Asp peptide ([¹⁸F]Galacto-RGD) PET for noninvasive imaging of α_vβ₃ expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [¹⁸F]Galacto-RGD PET. Standardized uptake values (SUVs) of tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [¹⁸F]Galacto-RGD PET images were fused with cranial MR images for image-guided surgery. Tumor samples taken from areas with intense tracer accumulation in the [¹⁸F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for α_vβ₃ integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 ± 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of tumors (mean SUV, 1.6 ± 0.5). Immunohistochemical staining was prominent in tumor microvessels as well as glial tumor cells. In areas of highly proliferating glial tumor cells, tracer uptake (SUVs) in the [¹⁸F]Galacto-RGD PET images correlated with immunohistochemical α_vβ₃ integrin expression of corresponding tumor samples. These data suggest that [¹⁸F] Galacto-RGD PET successfully identifies α_vβ₃ expression in patients with GBM and might be a promising tool for planning and monitoring individualized cancer therapies targeting this integrin.     

Mortality among Thorotrast-exposed patients and an unexposed comparison group in the German Thorotrast study

Thorotrast was the brand name of a stabilised colloidal solution of thorium dioxide which was used preferentially as an X-ray contrast medium for arteriography between 1930 and 1950. The administration of the medium led to lifelong chronic α-particle irradiation by thorium decay products, mainly in the organs of deposition. Several epidemiological follow-up studies were set up after recognition of these side-effects among which the German study was the largest. After an extended follow-up, by 2004 only nine out of 2326 originally exposed subjects were still alive (while 151 of the comparison group, which originally numbered 1890 subjects, survived) and partially more than 70 years observation and chronic exposure time could be studied allowing for further observations to be made about long-term mortality effects of Thorotrast exposure. Median life-expectancy was shortened by 14 years and mortality increased, affecting total mortality SMR = 287 for males, SMR = 387 for females) as well as cause-specific, especially liver cancer (SMR = 16,695 and SMR = 12,680, respectively), and the haematopoietic system (SMR = 556 and SMR = 504, respectively), but not lung cancer. Mortality (total and selected cause-specific) increased with cumulative time since first exposure.     

CD133 expression is an independent prognostic marker for low survival in colorectal cancer

Colon cancer cells have previously been demonstrated to contain a subpopulation of CD133+ tumour cells that have the ability to initiate tumour growth and are thus referred to as colon cancer-initiating cells or colon cancer stem cells (CSCs). As CD133 is currently one of the best markers to characterise colon CSCs, we analysed CD133+ tumour cells in colorectal cancer specimens using immunohistochemistry. We show that CD133 detection is specific and that the CD133 antigen is localised on the glandular-luminal surface of colon cancer cells, whereas undifferentiated tumour cells at the front of invasion are CD133-. In addition, CD133+ cells are characterised in situ by lack of CK20 expression, whereas they are positive for EpCAM. Moreover, we show that CD133 expression in colorectal cancer is an independent prognostic marker that correlates with low survival in a stratified patient collective. Our results indicate that in colorectal cancer, the CD133+ tumour cells can be detected by immunohistochemistry, which facilitates their further characterisation in situ.     

Relationship between habitual refractive errors and headache complaints in schoolchildren.

PURPOSE: Refractive error (RE) is considered to be a possible cause for headaches. We aimed to gain insight into the relation between habitual RE (sphere and astigmatism) and headache complaints. METHODS: In a cross-sectional study the habitual refractive state of 487 children, aged between 11 and 13 years, was measured using an autorefractometer (Topcon, RM-8000B). Headache complaints were measured using a questionnaire. Data were analyzed using Pearson correlation coefficients, bivariate analysis, and multiple logistic regression analysis. RESULTS: For right eyes we found 15% habitual myopia < -0.50 D and 12% habitual hyperopia > +0.50 D; habitual astigmatism > 0.25 D was found in 33% of children. Pearson R between right and left eyes was 0.76 for the spherical component and 0.42 for the cylindrical. In the total group of children 70% reported the occurrence of headache in the last year. These headaches were reported as "often or frequent" by 37% of children, "severe" by 15%, "with long duration" by 45%, and "with severe burden" by 27%. In the total sample we found various associations between gender, sphere/cylinder components of habitual RE, and headache complaints. Headache was reported more in girls than in boys. Of the total variance of headache complaints in girls, the sphere component of habitual RE explained 4% of frequency, 6% of intensity, 2% of duration, and 2% of amount of burden. Of the total variance of headache complaints in boys the cylinder component of habitual RE explained 3% of frequency, and 4% in amount of burden. CONCLUSION: Habitual RE and headache complaints are relatively common conditions in schoolchildren aged between 11 and 13 years. Headache complaints showed a small but statistically significant association with the sphere component of habitual RE in girls and the cylinder component of habitual RE in boys. The associations found between habitual RE and headache complaints indicate that habitual RE might be a risk factor for headache in children.