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      Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

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          Abstract

          Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.

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          Radiotherapy toxicity

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            Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis.

            Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P 0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location. Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Association Between Interstitial Lung Abnormalities and All-Cause Mortality.

              Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.
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                Author and article information

                Contributors
                lkaesmann@gmail.com
                alexander.dietrich@lrz.uni-muenchen.de
                staab-weijnitz@helmholtz-muenchen.de
                farkhad.manapov@med.uni-muenchen.de
                juergen.behr@med.uni-muenchen.de
                rimnera@mskcc.org
                nebareje@gmail.com
                s.senan@amsterdamumc.nl
                dirk.deruysscher@maastro.nl
                kirsten.lauber@med.uni-muenchen.de
                claus.belka@med.uni-muenchen.de
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                10 September 2020
                10 September 2020
                2020
                : 15
                : 214
                Affiliations
                [1 ]Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistrasse 15, 81377 Munich, Germany
                [2 ]GRID grid.452624.3, German Center for Lung Research (DZL), partner site Munich, ; Munich, Germany
                [3 ]German Cancer Consortium (DKTK), partner site Munich, Munich, Germany
                [4 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Walther Straub Institute of Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Medical Faculty, LMU-Munich, ; Munich, Germany
                [5 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Institute of Lung Biology and Disease, , Helmholtz Zentrum München, ; Munich, Germany
                [6 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Internal Medicine V, LMU Munich, ; Munich, Germany
                [7 ]GRID grid.51462.34, ISNI 0000 0001 2171 9952, Department of Radiation Oncology, , Memorial Sloan Kettering Cancer Center, ; New York, USA
                [8 ]Research Institute of Clinical Medicine, Tbilisi, Georgia
                [9 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Radiation Oncology, , Amsterdam University Medical Centers, ; Amsterdam, Netherlands
                [10 ]GRID grid.412966.e, ISNI 0000 0004 0480 1382, Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, , Maastricht University Medical Centre, ; Maastricht, the Netherlands
                Author information
                http://orcid.org/0000-0001-6260-5249
                Article
                1654
                10.1186/s13014-020-01654-9
                7488099
                32912295
                f40c072e-6e57-47fa-a70a-f52fee0d40d0
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 1 July 2020
                : 20 August 2020
                Funding
                Funded by: Metiphys
                Funded by: FundRef http://dx.doi.org/10.13039/501100010564, Deutsche Zentrum für Lungenforschung;
                Funded by: German Cancer Consortium
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: GRK 2338
                Award ID: GRK 2338
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;
                Award ID: "ZiSStrans" 02NUK047C
                Award Recipient :
                Funded by: National Institutes of Health (US)
                Award ID: Cancer Center Support Grant P30 CA008748
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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