| 1. |
- Bernchou, Uffe, et al.
(författare)
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End-to-end validation of the geometric dose delivery performance of MR linac adaptive radiotherapy
- 2021
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 66:4
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Tidskriftsartikel (refereegranskat)abstract
- The clinical introduction of hybrid magnetic resonance (MR) guided radiotherapy (RT) delivery systems has led to the need to validate the end-to-end dose delivery performance on such machines. In the current study, an MR visible phantom was developed and used to test the spatial deviation between planned and delivered dose at two 1.5 T MR linear accelerator (MR linac) systems, including pre-treatment imaging, dose planning, online imaging, image registration, plan adaptation, and dose delivery. The phantom consisted of 3D printed plastic and MR visible silicone rubber. It was designed to minimise air gaps close to the radiochromic film used as a dosimeter. Furthermore, the phantom was designed to allow submillimetre, reproducible positioning of the film in the phantom. At both MR linac systems, 54 complete adaptive, MR guided RT workflow sessions were performed. To test the dose delivery performance of the MR linac systems in various adaptive RT (ART) scenarios, the sessions comprised a range of systematic positional shifts of the phantom and imaging or plan adaptation conditions. In each workflow session, the positional translation between the film and the adaptive planned dose was determined. The results showed that the accuracy of the MR linac systems was between 0.1 and 0.9 mm depending on direction. The highest mean deviance observed was in the posterior-anterior direction, and the direction of the error was consistent between centres. The precision of the systems was related to whether the workflow utilized the internal image registration algorithm of the MR linac. Workflows using the internal registration algorithm led to a worse precision (0.2-0.7 mm) compared to workflows where the algorithm was decoupled (0.2 mm). In summary, the spatial deviation between planned and delivered dose of MR-guided ART at the two MR linac systems was well below 1 mm and thus acceptable for clinical use.
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| 2. |
- Blumel, Edda, et al.
(författare)
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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
- 2019
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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| 3. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 4. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 5. |
- Fogliata, Antonella, et al.
(författare)
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On the dosimetric behaviour of photon dose calculation algorithms in the presence of simple geometric heterogeneities: comparison with Monte Carlo calculations
- 2007
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 52:5, s. 1363-1385
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Tidskriftsartikel (refereegranskat)abstract
- A comparative study was performed to reveal differences and relative figures of merit of seven different calculation algorithms for photon beams when applied to inhomogeneous media. The following algorithms were investigated: Varian Eclipse: the anisotropic analytical algorithm, and the pencil beam with modified Batho correction; Nucletron Helax-TMS: the collapsed cone and the pencil beam with equivalent path length correction; CMS XiO: the multigrid superposition and the fast Fourier transform convolution; Philips Pinnacle: the collapsed cone. Monte Carlo simulations ( MC) performed with the EGSnrc codes BEAMnrc and DOSxyznrc from NRCC in Ottawa were used as a benchmark. The study was carried out in simple geometrical water phantoms(rho = 1.00 g cm(-3)) with inserts of different densities simulating light lung tissue (rho = 0.035 g cm(-3)), normal lung (rho = 0.20 g cm(-3)) and cortical bone tissue (rho = 1.80 g cm(-3)). Experiments were performed for low- and high-energy photon beams (6 and 15 MV) and for square (13 x 13 cm(2)) and elongated rectangular (2.8 x 13 cm(2)) fields. Analysis was carried out on the basis of depth dose curves and transverse profiles at several depths. Assuming the MC data as reference,. index analysis was carried out distinguishing between regions inside the non-water inserts or inside the uniformwater. For this study, a distance to agreement was set to 3 mm while the dose difference varied from 2% to 10%. In general all algorithms based on pencil-beam convolutions showed a systematic deficiency in managing the presence of heterogeneous media. In contrast, complicated patterns were observed for the advanced algorithmswith significant discrepancies observed between algorithms in the lighter materials (rho = 0.035 g cm(-3)), enhanced for the most energetic beam. For denser, and more clinical, densities a better agreement among the sophisticated algorithms with respect to MC was observed.
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| 6. |
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| 7. |
- Knöös, Tommy, et al.
(författare)
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Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations.
- 2006
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 51:22, s. 5785-5807
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Tidskriftsartikel (refereegranskat)abstract
- A study of the performance of five commercial radiotherapy treatment planning systems ( TPSs) for common treatment sites regarding their ability to model heterogeneities and scattered photons has been performed. The comparison was based on CT information for prostate, head and neck, breast and lung cancer cases. The TPSs were installed locally at different institutions and commissioned for clinical use based on local procedures. For the evaluation, beam qualities as identical as possible were used: low energy ( 6 MV) and high energy ( 15 or 18 MV) x-rays. All relevant anatomical structures were outlined and simple treatment plans were set up. Images, structures and plans were exported, anonymized and distributed to the participating institutions using the DICOM protocol. The plans were then re-calculated locally and exported back for evaluation. The TPSs cover dose calculation techniques from correction-based equivalent path length algorithms to model-based algorithms. These were divided into two groups based on how changes in electron transport are accounted for (( a) not considered and ( b) considered). Increasing the complexity from the relatively homogeneous pelvic region to the very inhomogeneous lung region resulted in less accurate dose distributions. Improvements in the calculated dose have been shown when models consider volume scatter and changes in electron transport, especially when the extension of the irradiated volume was limited and when low densities were present in or adjacent to the fields. A Monte Carlo calculated algorithm input data set and a benchmark set for a virtual linear accelerator have been produced which have facilitated the analysis and interpretation of the results. The more sophisticated models in the type b group exhibit changes in both absorbed dose and its distribution which are congruent with the simulations performed by Monte Carlo-based virtual accelerator.
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| 8. |
- Nielsen, Tine B., et al.
(författare)
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Influence of dose calculation algorithms on the predicted dose distributions and NTCP values for NSCLC patients
- 2011
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Ingår i: Medical Physics. - : Wiley. - 0094-2405. ; 38:5, s. 2412-2418
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate differences in calculated doses and normal tissue complication probability (NTCP) values between different dose algorithms. Methods: Six dose algorithms from four different treatment planning systems were investigated: Eclipse AAA, Oncentra MasterPlan Collapsed Cone and Pencil Beam, Pinnacle Collapsed Cone and XiO Multigrid Superposition, and Fast Fourier Transform Convolution. Twenty NSCLC patients treated in the period 2001-2006 at the same accelerator were included and the accelerator used for treatments were modeled in the different systems. The treatment plans were recalculated with the same number of monitor units and beam arrangements across the dose algorithms. Dose volume histograms of the GTV, PTV, combined lungs (excluding the GTV), and heart were exported and evaluated. NTCP values for heart and lungs were calculated using the relative seriality model and the LKB model, respectively. Furthermore, NTCP for the lungs were calculated from two different model parameter sets. Calculations and evaluations were performed both including and excluding density corrections. Results: There are found statistical significant differences between the calculated dose to heart, lung, and targets across the algorithms. Mean lung dose and V-20 are not very sensitive to change between the investigated dose calculation algorithms. However, the different dose levels for the PTV averaged over the patient population are varying up to 11%. The predicted NTCP values for pneumonitis vary between 0.20 and 0.24 or 0.35 and 0.48 across the investigated dose algorithms depending on the chosen model parameter set. The influence of the use of density correction in the dose calculation on the predicted NTCP values depends on the specific dose calculation algorithm and the model parameter set. For fixed values of these, the changes in NTCP can be up to 45%. Conclusions: Calculated NTCP values for pneumonitis are more sensitive to the choice of algorithm than mean lung dose and V-20 which are also commonly used for plan evaluation. The NTCP values for heart complication are, in this study, not very sensitive to the choice of algorithm. Dose calculations based on density corrections result in quite different NTCP values than calculations without density corrections. It is therefore important when working with NTCP planning to use NTCP parameter values based on calculations and treatments similar to those for which the NTCP is of interest. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3575418]
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| 9. |
- Obel, Carsten, et al.
(författare)
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Smoking during pregnancy and hyperactivity-inattention in the offspring—comparing results from three Nordic cohorts
- 2009
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 38:3, s. 698-705
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Tidskriftsartikel (refereegranskat)abstract
- Background Prenatal exposure to smoking has been associated with Attention Deficit Hyperactivity Disorder (ADHD) in a number of epidemiological studies. However, mothers with the ADHD phenotype may ‘treat’ their problem by smoking and therefore be more likely to smoke even in a society where smoking is not acceptable. This will cause genetic confounding if ADHD has a heritable component, especially in populations with low prevalence rates of smoking since this reason for smoking is expected to be proportionally more frequent in a population with few ‘normal’ smokers. We compared the association in cohorts with different smoking frequencies. Methods A total of 20 936 women with singleton pregnancies were identified within three population-based pregnancy cohorts in Northern Finland (1985–1986) and in Denmark (1984–1987 and 1989–1991). We collected self-reported data on their pre-pregnancy and pregnancy smoking habits and followed the children to school age where teachers and parents rated hyperactivity and inattention symptoms. Results Children, whose mothers smoked during pregnancy, had an increased prevalence of a high hyperactivity-inattention score compared with children of nonsmokers in each of the cohorts after adjustment for confounders but we found no statistical significant difference between the associations across the cohorts. Conclusion The estimated association was not strongest in the population with the fewest smokers which does not support the hypothesis that the association is entirely due to genetic confounding.
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| 10. |
- Skripcak, Tomas, et al.
(författare)
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Creating a data exchange strategy for radiotherapy research : Towards federated databases and anonymised public datasets
- 2014
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 113:3, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate 'translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within "Big Data". Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology.
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