Dosimetric consequences of the shift towards computed tomography guided target definition and planning for breast conserving radiotherapy

Background: The shift from conventional two-dimensional (2D) to three-dimensional (3D)conformal target definition and dose-planning seems to have introduced volumetric as well as geometric changes. The purpose of this study was to compare coverage of computed tomography (CT)-based breast and boost planning target volumes (PTV), absolute volumes irradiated, and dose delivered to the organs at risk with conventional 2D and 3D-conformal breast conserving radiotherapy. Methods: Twenty-five patients with left-sided breast cancer were subject of CT-guided target definition and 3D-conformal dose-planning, and conventionally defined target volumes and treatment plans were reconstructed on the planning CT. Accumulated dose-distributions were calculated for the conventional and 3D-conformal dose-plans, taking into account a prescribed dose of 50 Gy for the breast plans and 16 Gy for the boost plans. Results: With conventional treatment plans, CT-based breast and boost PTVs received the intended dose in 78% and 32% of the patients, respectively, and smaller volumes received the prescribed breast and boost doses compared with 3D-conformal dose-planning. The mean lung dose, the volume of the lungs receiving > 20 Gy, the mean heart dose, and volume of the heart receiving > 30 Gy were significantly less with conventional treatment plans. Specific areas within the breast and boost PTVs systematically received a lower than intended dose with conventional treatment plans. Conclusion: The shift towards CT-guided target definition and planning as the golden standard for breast conserving radiotherapy has resulted in improved target coverage at the cost of larger irradiated volumes and an increased dose delivered to organs at risk. Tissue is now included into the breast and boost target volumes that was never explicitly defined or included with conventional treatment. Therefore, a coherent definition of the breast and boost target volumes is needed, based on clinical data confirming tumour control probability and normal tissue complication probability with the use of 3D-conformal radiotherapy

Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: A dosimetric comparison

<p>Abstract</p> <p>Background</p> <p>This study evaluates the dose distribution of reversed planned tangential beam intensity modulated radiotherapy (IMRT) compared to standard wedged tangential beam three-dimensionally planned conformal radiotherapy (3D-CRT) of the chest wall in unselected postmastectomy breast cancer patients</p> <p>Methods</p> <p>For 20 unselected subsequent postmastectomy breast cancer patients tangential beam IMRT and tangential beam 3D-CRT plans were generated for the radiotherapy of the chest wall. The prescribed dose was 50 Gy in 25 fractions. Dose-volume histograms were evaluated for the PTV and organs at risk. Parameters of the dose distribution were compared using the Wilcoxon matched pairs test.</p> <p>Results</p> <p>Tangential beam IMRT statistically significantly reduced the ipsilateral mean lung dose by an average of 21% (1129 cGy versus 1437 cGy). In all patients treated on the left side, the heart volume encompassed by the 70% isodose line (V70%; 35 Gy) was reduced by an average of 43% (5.7% versus 10.6%), and the mean heart dose by an average of 20% (704 cGy versus 877 cGy). The PTV showed a significantly better conformity index with IMRT; the homogeneity index was not significantly different.</p> <p>Conclusions</p> <p>Tangential beam IMRT significantly reduced the dose-volume of the ipsilateral lung and heart in unselected postmastectomy breast cancer patients.</p

Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes

Background Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with 24,072 gene probe sets representing more than 23,000 gene transcripts. Results Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of gene transcripts showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity® Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. Conclusions This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.This work was supported by Investigator Grants from Science Foundation Ireland (Nos: SFI/01/F.1/B028 and SFI/08/IN.1/B2038), a Research Stimulus Grant from the Department of Agriculture, Fisheries and Food (No: RSF 06 405) and a European Union Framework 7 Project Grant (No: KBBE-211602-MACROSYS). KEK is supported by the Irish Research Council for Science, Engineering and Technology (IRCSET) funded Bioinformatics and Systems Biology PhD Programme http://bioinfo-casl.ucd.ie/PhD

Voedselconsumptiepeiling bij peuters en kleuters 2005/2006

Peuters en kleuters in Nederland eten te weinig groenten, fruit, vis en vezelrijke voedingsmiddelen. Bovendien bevat de voeding van kleuters te veel verzadigde vetzuren. De ongezonde voeding van deze generatie kinderen kan leiden tot overgewicht en op latere leeftijd tot chronische ziekten. Beleid is nodig om een gunstig lichaamsgewicht te bevorderen en om de consumptie van groenten, fruit, vis, vezelrijke producten en voedingsmiddelen met een goede vetzuursamenstelling te stimuleren. Een peiling onder kinderen van 2 tot en met 6 jaar laat zien dat het aandeel van vet, eiwitten en koolhydraten in hun voeding goed is. Wel is het type vet in de voeding van veel jonge kinderen ongunstig. Ze eten te weinig vis (rijk aan visvetzuren) en vooral de voeding van kleuters bevat te veel verzadigde vetzuren. Daarnaast zijn er weinig jonge kinderen die voldoende groenten eten. Voor fruit is het beeld iets gunstiger: een op de vier jonge kinderen eet de geadviseerde hoeveelheid. Verder is een op de zeven kinderen in mindere of meerdere mate te dik. Het lijkt erop dat zij dus meer energie binnenkrijgen dan verbruiken. Jonge kinderen krijgen van de meeste vitamines en mineralen voldoende binnen. Van vitamine D en foliumzuur is de inname echter laag. Slechts drie op de vijf peuters gebruikt een supplement met vitamine D. Vervolgonderzoek is nodig om vast te stellen of daadwerkelijk sprake is van tekorten. Bovendien is nader onderzoek nodig naar de gevolgen van een hoge inname van zink, koper, retinol (een type vitamine A) en synthetisch foliumzuur bij een deel van de kinderen.Young children in the Netherlands aged 2 to 6 years do not consume sufficient amounts of vegetables, fruit, fish and fibre. In addition the intake of saturated fatty acids is higher than recommended in the 4 to 6 year-old age group. This unhealthy diet can lead to overweight, and later in life to chronic diseases. Policy measures need to focus on achieving optimal body weight, increasing intakes of vegetables, fruit, fish and fibre, and improving the fatty acid composition in the diet of young children. A food consumption survey of young children (2 to 6 years of age) in the Netherlands has shown the diet to be adequate in terms of the proportions of total fat, carbohydrates and protein. However, the fatty acid composition of the diet isunfavourable, because fish consumption (rich in fish fatty acids) is low, and saturated fatty acid intake especially in 4 to 6 year-old children is high. Only a small proportion of children meet the recommended vegetable intake. For fruit the situation is slightly more favourable (one in four). Furthermore, one in seven children was found to be overweight or obese, indicating a positive energy balance in the period prior to the study. Intakes of most vitamins and minerals were shown to be adequate, with the exception of vitamin D and folate. Only three in five children aged 2 to 3 years received the recommended vitamin D containing supplements. The implications of the low intakes of vitamin D and folate and the high intakes of zinc, retinol, synthetic folic acid and copper need to be investigated.VW