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- Unterrainer, M., et al.
(författare)
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Recent advances of PET imaging in clinical radiation oncology
- 2020
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.
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- Belka, C., et al.
(författare)
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The tyrosine kinase Lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation
- 1999
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 18:35, s. 4983-4992
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Tidskriftsartikel (refereegranskat)abstract
- Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis, Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck, Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression, This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.
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- Guninski, R. S., et al.
(författare)
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Efficacy and safety of SBRT for spine metastases : A systematic review and meta-analysis for preparation of an ESTRO practice guideline
- 2023
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Ingår i: Radiotherapy and Oncology. - 0167-8140.
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Advances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many patients with metastatic disease. Palliative radiotherapy needs to adapt to these developments. In this study, we summarize the available evidence for stereotactic body radiotherapy (SBRT) in the treatment of spinal metastases. Materials and methods: A systematic review and meta-analysis was performed using PRISMA methodology, including publications from January 2005 to September 2021, with the exception of the randomized phase III trial RTOG-0631 which was added in April 2023. Re-irradiation was excluded. For meta-analysis, a random-effects model was used to pool the data. Heterogeneity was assessed with the I2-test, assuming substantial and considerable as I2 > 50 % and I2 > 75 %, respectively. A p-value < 0.05 was considered statistically significant. Results: A total of 69 studies assessing the outcomes of 7236 metastases in 5736 patients were analyzed. SBRT for spine metastases showed high efficacy, with a pooled overall pain response rate of 83 % (95 % confidence interval [CI] 68 %-94 %), pooled complete pain response of 36 % (95 % CI: 20 %-53 %), and 1-year local control rate of 94 % (95 % CI: 86 %-99 %), although with high levels of heterogeneity among studies (I2 = 93 %, I2 = 86 %, and 86 %, respectively). Furthermore, SBRT was safe, with a pooled vertebral fracture rate of 9 % (95 % CI: 4 %-16 %), pooled radiation induced myelopathy rate of 0 % (95 % CI 0–2 %), and pooled pain flare rate of 6 % (95 % CI: 3 %-17 %), although with mixed levels of heterogeneity among the studies (I2 = 92 %, I2 = 0 %, and 95 %, respectively). Only 1.7 % of vertebral fractures required surgical stabilization. Conclusion: Spine SBRT is characterized by a favorable efficacy and safety profile, providing durable results for pain control and disease control, which is particularly relevant for oligometastatic patients.
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- Moreau, V., et al.
(författare)
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Pool CFD modelling : lessons from the SESAME project
- 2019
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Ingår i: Nuclear Engineering and Design. - : ELSEVIER SCIENCE SA. - 0029-5493 .- 1872-759X. ; 355
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Tidskriftsartikel (refereegranskat)abstract
- The current paper describes the Computational Fluid-Dynamics (CFD) modelling of Heavy Liquid Metal (HLM) flows in a pool configuration and in particular how this is approached within the Horizon 2020 SESAME project. SESAME's work package structure, based on a systematic approach of redundancy and diversification, is explained along with its motivation. The main achievements obtained and the main lessons learned during the project are illustrated. The paper focuses on the strong coupling between the experimental activities and CFD simulations performed within the SESAME project. Two different HLM fluids are investigated: pure lead and Lead-Bismuth Eutectic. The objective is to make CFD a valid instrument used during the design of safe and innovative Gen-IV nuclear plants. Some effort has also been devoted to Proper Orthogonal Decomposition with Galerkin projection modelling (POD-Galerkin), a reduced order model suited for Uncertainty Quantification that operates by post-processing CFD results. Assessment of Uncertainty highly improves the reliability of CFD simulations. Dedicated experimental campaigns on heavily instrumented facilities have been conceived with the specific objective to build a series of datasets suited for the calibration and validation of the CFD modelling. In pool configuration, the attention is focused on the balance between conductive and convective heat transfer phenomena, on transient test-cases representative of incidental scenarios and on the possible occurrence of solidification phenomena. Four test sections have been selected to generate the datasets: (i) the CIRCE facility from ENEA, (ii) the TALL-3D pool test section from KTH, (iii) the TALL-3D Solidification Test Section (STS) from KTH and (iv) the SESAME Stand facility from CVR. While CIRCE and TALL-3D were existing facilities, the STS and SESAME Stand facility have been conceived, built and operated within the project, heavily relying on the use of CFD support. Care has been taken to ensure that almost all tasks were performed by at least two partners. Specific examples are given on how this strategy has allowed to uncover flaws and overcome pitfalls. Furthermore, an overview of the performed work and the achieved results is presented, as well as remaining or new uncovered issues. Finally, the paper is concluded with a description of one of the main goals of the SESAME project: the construction of the Gen-IV ALFRED CFD model and an investigation of its general circulation.
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- Niyazi, Maximilian, et al.
(författare)
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ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma
- 2023
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Ingår i: Radiotherapy and Oncology. - 0167-8140. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Target delineation in glioblastoma is still a matter of extensive research and debate. This guideline aims to update the existing joint European consensus on delineation of the clinical target volume (CTV) in adult glioblastoma patients. Material and Methods: The ESTRO Guidelines Committee identified 14 European experts in close interaction with the ESTRO clinical committee and EANO who discussed and analysed the body of evidence concerning contemporary glioblastoma target delineation, then took part in a two-step modified Delphi process to address open questions. Results: Several key issues were identified and are discussed including i) pre-treatment steps and immobilisation, ii) target delineation and the use of standard and novel imaging techniques, and iii) technical aspects of treatment including planning techniques and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a reduced 15 mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. Conclusions: The EORTC consensus recommends a single clinical target volume definition based on postoperative contrast-enhanced T1 abnormalities, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised; this should usually be no greater than 3 mm when using IGRT.
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| 8. |
- Renz, A., et al.
(författare)
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Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
- 2001
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 98:5, s. 1542-1548
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Tidskriftsartikel (refereegranskat)abstract
- Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell Is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemo-therapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c In the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo. (C) 2001 by The American Society of Hematology.
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