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      MR Image Changes of Normal-Appearing Brain Tissue after Radiotherapy


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          Radiotherapy is one of the most important treatment options against cancer. Irradiation of cancerous tissue either directly destroys the cancer cells or damages them such that they cannot reproduce. One side-effect of radiotherapy is that tumor-surrounding normal tissue is inevitably also irradiated, albeit at a lower dose. The resulting long-term damage can significantly affect cognitive performance and quality of life. Many studies investigated the effect of irradiation on normal-appearing brain tissues and some of these correlated imaging findings with functional outcome. This article provides an overview of the examination of radiation-induced injuries using conventional and enhanced MRI methods and summarizes conclusions about the underlying tissue changes. Radiation-induced morphologic, microstructural, vascular, and metabolic tissue changes have been observed, in which the effect of irradiation was evident in terms of decreased perfusion and neuronal health as well as increased diffusion and atrophy.


          Radiotherapy is part of the standard treatment of most primary brain tumors. Large clinical target volumes and physical characteristics of photon beams inevitably lead to irradiation of surrounding normal brain tissue. This can cause radiation-induced brain injury. In particular, late brain injury, such as cognitive dysfunction, is often irreversible and progressive over time, resulting in a significant reduction in quality of life. Since 50% of patients have survival times greater than six months, radiation-induced side effects become more relevant and need to be balanced against radiation treatment given with curative intent. To develop adequate treatment and prevention strategies, the underlying cause of radiation-induced side-effects needs to be understood. This paper provides an overview of radiation-induced changes observed in normal-appearing brains measured with conventional and advanced MRI techniques and summarizes the current findings and conclusions. Brain atrophy was observed with anatomical MRI. Changes in tissue microstructure were seen on diffusion imaging. Vascular changes were examined with perfusion-weighted imaging and susceptibility-weighted imaging. MR spectroscopy revealed decreasing N-acetyl aspartate, indicating decreased neuronal health or neuronal loss. Based on these findings, multicenter prospective studies incorporating advanced MR techniques as well as neurocognitive function tests should be designed in order to gain more evidence on radiation-induced sequelae.

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          Most cited references 145

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          Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

          In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.
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            Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies

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              A voxel-based morphometric study of ageing in 465 normal adult human brains.

              Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

                Author and article information

                Role: Academic Editor
                Cancers (Basel)
                Cancers (Basel)
                29 March 2021
                April 2021
                : 13
                : 7
                [1 ]Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology—OncoRay, Dresden, Germany; Katharina.Witzmann@ 123456uniklinikum-dresden.de (K.W.); felix.raschke@ 123456oncoray.de (F.R.)
                [2 ]OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
                [3 ]Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
                [4 ]German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
                [5 ]National Center for Tumor Diseases (NCT), Partner Site Dresden of the German Cancer Research Center (DKFZ), Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
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                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).



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